Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

The decreases of HbA 1c in those using BGM were similar to the decreases in comparably treated people who did not use BGM.

“The decreases of HbA 1c in those using BGM were similar to the decreases in comparably treated people who did not use BGM.”

• cites [111] Malanda, 2012, Self-monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin, Cochrane Database Syst Rev sourcePartly supported

  The Glycaemic control measured by HbA1c section reports that several studies found HbA1c improvements in both groups without a statistically significant difference. But the Subgroup analyses section reports a statistically significant 0.3-percentage-point greater decrease with self-monitoring at up to six months, so the unqualified statement that the decreases were similar overstates the review's findings. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [112] Farmer, 2012, Meta-analysis of individual patient data in randomised trials of self monitoring of blood glucose in people with non-insulin treated type 2 diabetes, BMJ sourceSupported
• cites [113] Machry, 2018, Self-monitoring blood glucose improves glycemic control in type 2 diabetes without intensive treatment: a systematic review and meta-analysis, Diabetes Res Clin Pract sourceNot checked — no full text of the source
• cites [114] Mannucci, 2018, Effects of structured versus unstructured self-monitoring of blood glucose on glucose control in patients with non-insulin-treated type 2 diabetes: a meta-analysis of randomized controlled trials, J Diabetes Sci Technol sourceDisputed

  In “Trials Comparing SMBG with no SMBG” (p. 3), the paper reports a statistically significant greater reduction in HbA1c with self-monitoring than without it (−0.17 percentage points in the full dataset). The Discussion (p. 5) likewise calls the reduction small but significant, rather than similar between groups. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

The presence of multiple islet autoantibodies (IAA, GADA, IA-2A/IA-2bA, or ZnT8A) is associated with a risk of type 1 diabetes of >90%.

“The presence of multiple islet autoantibodies (IAA, GADA, IA-2A/IA-2bA, or ZnT8A) is associated with a risk of type 1 diabetes of >90% (408,422,423).”

• cites [408] Ziegler, 2013, Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children, JAMA sourceDisputed

  The Results section (Children With Multiple Islet Autoantibodies; page unavailable) confirms that multiple autoantibodies are associated with high risk, but reports progression of 69.7% at 10 years and 84.2% at 15 years—not greater than 90%. Adding ZnT8 autoantibodies did not substantially change the progression estimates in the cohorts where they were measured. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [422] Jacobsen, 2020, The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening, Diabetologia sourceDisputed

  The Results (Number and type of autoantibodies; page unavailable) report five-year diabetes incidences of 29% for participants with two autoantibodies and 31% for those with more than two. The Discussion says risk varies substantially after screening and that progression was questionable for a considerable number even with more than two autoantibodies. These five-year estimates do not establish lifetime risk, but the paper does not support the unqualified >90% risk attributed to it. (LLM, conf=0.83)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [423] Anand, 2021, Islet autoimmunity and HLA markers of presymptomatic and clinical type 1 diabetes: joint analyses of prospective cohort studies in Finland, Germany, Sweden, and the U.S, Diabetes Care sourcePartly supported

  The Results report a higher 15-year type 1 diabetes risk with multiple autoantibodies, but the risk exceeded 90% only in some groups: it was 92% with three autoantibodies at seroconversion, versus 85% with two. Table 2 also shows that risk varied by age at development of multiple autoantibodies. The unqualified >90% figure is therefore not supported; ZnT8A was measured but excluded from the primary analyses. (LLM, conf=0.91)

  Experimental — accuracy not yet measured

The evidence that population screening for hyperglycemia and subsequent prevention efforts will provide long-term benefit is inconsistent.

“Notwithstanding this recommendation, the evidence that population screening for hyperglycemia and subsequent prevention efforts will provide long-term benefit is inconsistent (27).”

• cites [27] Nathan, 2019, Does diabetes prevention translate into reduced long-term vascular complications of diabetes?, Diabetologia sourcePartly supported

  The Discussion (page unavailable) says evidence that diabetes prevention reduces long-term vascular complications is inconsistent. The paper assesses prevention studies, not population screening for hyperglycemia followed by prevention efforts, so it does not establish the claim for that broader strategy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

FPG increases with increasing age beginning in the third to fourth decade.

“FPG increases with increasing age beginning in the third to fourth decade (97,98).”

• cites [97] Tchobroutsky, 1991, Blood glucose levels in diabetic and non-diabetic subjects, Diabetologia sourceSupported
• cites [98] van den Beld, 2018, The physiology of endocrine systems with ageing, Lancet Diabetes Endocrinol sourceSupported

Careful evaluation over several consecutive days in normoglycemic individuals revealed that biological variation of FPG (mean glucose of 4.9 mmol/L [88 mg/dL]) exhibited within-and between-subject CVs of 4.8% to 6.1% and 7.5% to 7.8%, respectively.

“Careful evaluation over several consecutive days in normoglycemic individuals revealed that biological variation of FPG (mean glucose of 4.9 mmol/L [88 mg/dL]) exhibited within-and between-subject CVs of 4.8% to 6.1% and 7.5% to 7.8%, respectively (90)(91)(92).”

• cites [90] Widjaja, 1999, Within- and between-subject variation in commonly measured anthropometric and biochemical variables, Clin Chem sourceNot checked — no full text of the source
• cites [91] Mooy, 1996, Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study, Diabetologia sourcePartly supported

  The Abstract reports test–retest variation in fasting glucose among people with normal glucose tolerance. It does not give the claimed mean of 4.9 mmol/L, the within- and between-subject CV ranges, or an evaluation over several consecutive days; searches for those figures and terms found no supporting passage. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [92] Sebastián-Gámbaro, 1997, Intra- and inter-individual biological variability data bank, Eur J Clin Chem Clin BiochemNot checked — no full text of the source

Measurement of FPG in 246 normal and 80 previously undiagnosed individuals with diabetes revealed mean intraindividual CVs of 4.8% and 7.1%, respectively.

“Measurement of FPG in 246 normal and 80 previously undiagnosed individuals with diabetes revealed mean intraindividual CVs of 4.8% and 7.1%, respectively (91).”

• cites [91] Mooy, 1996, Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study, Diabetologia sourceCould not verify

  The available Abstract passage discusses fasting-glucose test–retest variation in people with normal glucose tolerance, but gives no mean intraindividual CVs. Searches for 246, 80, 4.8%, and 7.1% found no passage verifying the sample sizes or the values for either group. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

Glucose homeostasis is impaired with aging.

“Glucose homeostasis is impaired with aging.”

• cites [97] Tchobroutsky, 1991, Blood glucose levels in diabetic and non-diabetic subjects, Diabetologia sourceSupported
• cites [98] van den Beld, 2018, The physiology of endocrine systems with ageing, Lancet Diabetes Endocrinol sourceSupported

The meta-analysis by Farmer et al. found that the mean pooled reduction in HbA 1c was 0.88% in BGM-assigned groups and 0.69% in the usual care groups.

“For example, the meta-analysis by Farmer et al. (112) found that the mean pooled reduction in HbA 1c was 0.88% in BGMassigned groups and 0.69% in the usual care groups.”

• cites [112] Farmer, 2012, Meta-analysis of individual patient data in randomised trials of self monitoring of blood glucose in people with non-insulin treated type 2 diabetes, BMJ sourceSupported

Use of meters that meet the current ISO standard reduced the financial consequences of inaccuracy of glucose meters by more than £178 ($238) per patient-year.

“Use of meters that meet the current ISO standard reduced the financial consequences of inaccuracy of glucose meters by more than £178 ($238) per patient-year.”

• cites [128] Fortwaengler, 2018, The financial impact of inaccurate blood glucose monitoring systems, J Diabetes Sci Technol sourcePartly supported

  The Results (page unavailable) estimate £235 less inaccuracy-related cost per patient-year for an average meter meeting ISO 15197:2013 than for one failing ISO 15197:2003, which supports a reduction greater than £178 for that comparison. But the £178 figure itself compares meters failing and meeting the older 2003 standard; the paper reports modeled cost comparisons, not an observed reduction from using compliant meters. Our copy does not report the $238 figure. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Meta-analyses also reported that, by 1 year of use of BGM, the improvements in HbA 1c seen at earlier time points were lost.

“Meta-analyses also reported that, by 1 year of use of BGM, the improvements in HbA 1c seen at earlier time points were lost (111,113).”

• cites [111] Malanda, 2012, Self-monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin, Cochrane Database Syst Rev sourcePartly supported

  The Main results report a significant HbA1c decrease at up to six months but a statistically non-significant decrease at 12 months in patients whose diabetes duration was at least one year. The Subgroup analyses also report a significant decrease at 12 months in newly diagnosed patients. The claim captures the first finding but omits that qualification and describes a non-significant result as improvements being lost. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [113] Machry, 2018, Self-monitoring blood glucose improves glycemic control in type 2 diabetes without intensive treatment: a systematic review and meta-analysis, Diabetes Res Clin Pract sourceNot checked — no full text of the source

A pragmatic, open-label randomized trial found no clinically or statistically significant differences at 1 year in glycemic control (as assessed by HbA 1c) or health-related quality of life between patients who performed BGM, with or without enhanced feedback, and those who did not.

“The study found no clinically or statistically significant differences at 1 year in glycemic control (as assessed by HbA 1c ) or health-related quality of life between patients who performed BGM, with or without enhanced feedback, and those who did not.”

• cites [115] Young, 2017, Glucose self-monitoring in non–insulin-treated patients with type 2 diabetes in primary care settings: a randomized trial, JAMA Intern Med sourceSupported

In a 2017 study, only 2 of 17 commercial meters intended for home BGM use met the ISO standard.

“In a 2017 study, however, only 2 of 17 commercial meters intended for home BGM use met the ISO standard (125).”

• cites [125] Ekhlaspour, 2017, Comparative accuracy of 17 point-of-care glucose meters, J Diabetes Sci Technol sourcePartly supported

  The Results (‘Accuracy Based on ISO Criteria’) report that 2 of 17 meters met the ISO 2013 numerical accuracy criteria in this study, while 7 met the ISO 2003 criteria. The Discussion cautions that testing did not follow the ISO protocol, so the study does not establish that only two meters met an ISO standard under standard testing conditions. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

The anatomical site from which skin puncture samples are obtained influences results: use of blood from alternate sites (such as forearm or thigh rather than fingertip) may exhibit a temporal lag between the circulating and measured concentrations of glucose when blood glucose is changing in vivo.

“The anatomical site from which skin puncture samples are obtained influences results: Use of blood from so-called alternate sites (such as forearm or thigh rather than fingertip) for testing may exhibit a temporal lag between the circulating and measured concentrations of glucose when blood glucose is changing in vivo (117).”

• cites [117] Ellison, 2002, Rapid changes in postprandial blood glucose produce concentration differences at finger, forearm, and thigh sampling sites, Diabetes Care sourceSupported

Meters that are designed for professional use have been shown in published studies to be accurate on samples of whole blood.

“Meters that are designed for professional use have been shown in published studies to be accurate on samples of whole blood (129-131).”

• cites [129] Nichols, 2021, A multicenter evaluation of a point-of-care blood glucose meter system in critically ill patients, J Appl Lab Med sourceSupported
• cites [130] Mitsios, 2013, Analytic evaluation of a new glucose meter system in 15 different critical care settings, J Diabetes Sci Technol sourceSupported
• cites [131] Karon, 2015, Impact of glucose meter error on glycemic variability and time in target range during glycemic control after cardiovascular surgery, J Diabetes Sci Technol sourceNot checked — no full text of the source

The role of BGM in individuals with type 2 diabetes who are treated with only basal insulin or no insulin has generated considerable controversy.

“The role of BGM in individuals with type 2 diabetes who are treated with only basal insulin or no insulin has generated considerable controversy (109).”

• cites [109] American Diabetes Association, 2011, Standards of medical care in diabetes—2011, Diabetes Care sourcePartly supported

  The Recommendations section says the optimal use of self-monitoring in non–insulin-treated type 2 diabetes is unclear and that trials have questioned its clinical utility and cost-effectiveness. It says monitoring may be useful for people using less-frequent insulin injections, but does not describe comparable controversy specifically for basal-only insulin. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Except for the potential use of BGM in people with type 2 diabetes using insulin, BGM likely adds cost without benefit.

“However, except for the potential use of BGM in people with type 2 diabetes using insulin, BGM likely adds cost without benefit (110).”

• cites [110] Simon, 2008, Cost effectiveness of self monitoring of blood glucose in patients with non-insulin treated type 2 diabetes: economic evaluation of data from the DiGEM trial, BMJ sourcePartly supported

  The Abstract and Discussion (page not available in our copy) report higher costs and no clinically significant benefit from self-monitoring compared with standardised usual care. But the study concerns reasonably well-controlled people with non-insulin-treated type 2 diabetes; the Discussion cautions that its results may not apply to other groups. It does not establish the claim for everyone except those using insulin. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Analytical errors of meters that meet the 2013 ISO standard have only limited impact on the three outcome measures or on HbA 1c.

“Analytical errors of meters that meet the 2013 ISO standard have only limited impact on the three outcome measures or on HbA 1c .”

• cites [127] Campos-Náñez, 2017, Clinical impact of blood glucose monitoring accuracy: an in-silico study, J Diabetes Sci Technol sourceSupported

Numerous interfering factors have been reported to influence the results of blood glucose meters.

“Numerous interfering factors have been reported to influence the results of blood glucose meters (135,136).”

• cites [135] Erbach, 2016, Interferences and limitations in blood glucose self-testing: an overview of the current knowledge, J Diabetes Sci Technol sourceNot checked — no full text of the source
• cites [136] Tirimacco, 2013, Glucose meters—fit for clinical purpose, Clin Chem Lab Med sourceSupported

Several sugars-notably maltose, galactose, and xylose-falsely increase results of some glucose meters.

“Several sugars-notably maltose, galactose, and xylose-falsely increase results of some glucose meters.”

• cites [139] Perera, 2011, The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis, Diabet Med sourceNot checked — no full text of the source
• cites [133] Ceriotti, 2015, Comparative performance assessment of point-of-care testing devices for measuring glucose and ketones at the patient bedside, J Diabetes Sci Technol sourceNot checked — no full text of the source
• cites [140] Lv, 2013, Factors interfering with the accuracy of five blood glucose meters used in Chinese hospitals, J Clin Lab Anal sourcePartly supported

  The Discussion (page unavailable) says galactose and maltose increased readings on the Accu-Chek and FreeStyle meters at all three glucose levels tested. The paper does not report testing xylose, so it does not support that part of the claim. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

A later study found a strong, continuous association of BGM frequency with improved glycemic control as measured by HbA 1c.

“A later study found a strong, continuous association of BGM frequency with improved glycemic control as measured by HbA 1c (150).”

• cites [150] Miller, 2013, Evidence of a strong association between frequency of self-monitoring of blood glucose and hemoglobin A1c levels in T1D exchange clinic registry participants, Diabetes Care sourcePartly supported

  The Results report a strong association between more frequent self-monitoring of blood glucose and lower HbA1c in all age groups. However, they also say the association appeared to level off at approximately 10 measurements per day, so “continuous” overstates the finding if it means improvement at every frequency. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Monitoring of blood glucose less frequently than three to four times per day in adults and adolescents has been associated with less effective control of glycemia as measured by HbA 1c.

“Monitoring of blood glucose less frequently than three to four times per day in adults and adolescents has been associated with less effective control of glycemia as measured by HbA 1c (150)(151)(152).”

• cites [150] Miller, 2013, Evidence of a strong association between frequency of self-monitoring of blood glucose and hemoglobin A1c levels in T1D exchange clinic registry participants, Diabetes Care sourceSupported
• cites [151] Ziegler, 2011, Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes, Pediatr Diabetes sourcePartly supported

  The Results report that more frequent monitoring was associated with lower HbA1c, and the Discussion specifies a marked improvement with 2–5 measurements per day among adolescents. The study covers children and adolescents, not adults, and does not establish a specific three-to-four-times-per-day threshold. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [152] Schütt, 2006, Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria, Exp Clin Endocrinol Diabetes sourceNot checked — no full text of the source

A subsequent RCT specifically targeting adolescents and young adults, which included considerable education and support, showed that those randomized to rt-CGM had significantly reduced HbA 1c after 6 months compared with those randomized to BGM.

“A subsequent RCT specifically targeting adolescents and young adults, which included considerable education and support, showed that those randomized to rt-CGM had significantly reduced HbA 1c after 6 months compared with those randomized to BGM (175).”

• cites [175] Laffel, 2020, Effect of continuous glucose monitoring on glycemic control in adolescents and young adults with type 1 diabetes: a randomized clinical trial, JAMA sourceSupported

A subsequent international consensus defined targets for most of the measures on the Ambulatory Glucose Profile that would correspond to individualized HbA1c targets.

“A subsequent international consensus defined targets for most of the measures on the AGP that would correspond to individualized HbA 1c targets (193).”

• cites [193] Battelino, 2019, Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range, Diabetes Care sourcePartly supported

  The Time in Ranges section (p. 10) sets personalized targets for time within, below, and above glucose ranges, and Standardization of CGM Data Presentation (p. 16) says the AGP incorporates core CGM metrics and targets. Relationship Between TIR and A1C (p. 14) gives approximate A1C values corresponding to time-in-range levels. The paper does not establish a correspondence between individualized HbA1c targets and most AGP measures; the stated A1C relationship is specifically for time in range. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Studies designed to establish correlations between blood and tear glucose concentrations are inconclusive from both human and animal studies.

“Studies designed to establish correlations between blood and tear glucose concentrations are inconclusive from both human (243-245) and animal studies (246).”

• cites [243] Baca, 2007, Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus, Ocul Surf sourceNot checked — no full text of the source
• cites [244] Baca, 2007, Mass spectral determination of fasting tear glucose concentrations in nondiabetic volunteers, Clin Chem sourceSupported
• cites [245] Cha, 2014, Evaluation of commercial glucometer test strips for potential measurement of glucose in tears, Anal Chem sourceNot checked — no full text of the source
• cites [246] Peng, 2013, Evaluation of enzyme-based tear glucose electrochemical sensors over a wide range of blood glucose concentrations, Biosens Bioelectron sourceNot checked — no full text of the source

Rates of several adverse neonatal outcomes (large-for-gestational-age infants, newborn intensive care unit admissions, neonatal hypoglycemia) were lower in the group randomized to rt-CGM.

“Rates of several adverse neonatal outcomes (large-forgestational-age infants, newborn intensive care unit admissions, neonatal hypoglycemia) were lower in the group randomized to rt-CGM (184).”

• cites [184] Feig, 2017, Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT): a multicentre international randomised controlled trial, Lancet sourceSupported

Some secondary outcomes, including risks of shoulder dystocia and/or birth injury and preeclampsia, were also associated with maternal glycemia.

“Some secondary outcomes, including risks of shoulder dystocia and/or birth injury and preeclampsia, were also associated with maternal glycemia (257).”

• cites [257] Yogev, 2010, Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia, Am J Obstet Gynecol sourcePartly supported

  The Results and Comment sections report that preeclampsia became more frequent as maternal glucose increased, although the association weakened after adjustment for C-peptide. Our copy does not report an association between maternal glycemia and shoulder dystocia or birth injury; searches for those outcomes found no supporting passage. No page numbers were provided. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The Diabetes Prevention Program (DPP) found that progression to diabetes can be delayed or prevented by intervention.

“In addition, women with GDM have a considerably increased risk of developing type 2 diabetes after pregnancy (273), and the Diabetes Prevention Program (DPP) found that progression to diabetes can be delayed or prevented by intervention (274); thus, long-term follow-up is important.”

• cites [274] Ratner, 2008, Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions, J Clin Endocrinol Metab sourceSupported

The cumulative risk of progression to diabetes after GDM is linear over time, reaching 50% to 60%.

“Since the cumulative risk of progression to diabetes after GDM is linear over time (reaching 50% to 60% [273,275]), women should be evaluated every 1 to 3 years with any recommended test of glycemia, e.g., annual HbA 1c , annual FPG, or triennial 75-g OGTT (with nonpregnant cutoffs) (251).”

• cites [273] Vounzoulaki, 2020, Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis, BMJ sourcePartly supported

  The Discussion (Comparison with other studies; page unavailable) says cumulative incidence increased steadily over time, which supports an increasing trend but does not establish that it was linear. The Results (Meta-analysis; page unavailable) report a pooled cumulative incidence of 16.15% in studies with more than 10 years of follow-up, not the claimed 50% to 60%. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [275] Li, 2020, Incidence rate of type 2 diabetes mellitus after gestational diabetes mellitus: a systematic review and meta-analysis of 170,139 women, J Diabetes Res sourceSupported

Follow-up of the children in both these studies at 4 to 5 and 7 years of age, respectively, failed to observe differences in limited indicators of child adiposity between children of mothers with treated GDM and those with untreated GDM.

“Follow-up of the children in both these studies at 4 to 5 (264-266) and 7 years of age (267), respectively, failed to observe differences in limited indicators of child adiposity between children of mothers with treated GDM and those with untreated GDM.”

• cites [264] Crowther, 2005, Effect of treatment of gestational diabetes mellitus on pregnancy outcomes, N Engl J Med sourceCould not verify

  The secondary outcomes section reports infant measurements at birth and explicitly says long-term follow-up is needed. A search for adiposity outcomes at ages 4–5 and 7 found no such follow-up results in our copy, so this paper cannot verify the claimed absence of differences at those ages. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [265] Landon, 2009, A multicenter, randomized trial of treatment for mild gestational diabetes, N Engl J Med sourceCould not verify

  The Results (Perinatal and Neonatal Outcomes; page unavailable) report birth weight and neonatal fat mass, not adiposity at ages 4–5 or 7. The Discussion says long-term follow-up studies are needed to determine whether treatment affects childhood outcomes. Searches for follow-up and childhood adiposity found no results at either age in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [266] Gillman, 2010, Effect of treatment of gestational diabetes mellitus on obesity in the next generation, Diabetes Care sourcePartly supported

  The Conclusions report no reduction in BMI after treatment of mild GDM, supporting the null finding. But citation 267 is attached to the seven-year follow-up, whereas this paper measured children at ages 4–5; the Conclusions say its height-and-weight surveillance did not extend past age five. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [267] Landon, 2015, Mild gestational diabetes mellitus and long-term child health, Diabetes Care sourceSupported

Comparison of glucose measured in samples collected in sodium fluoride-containing tubes kept in an ice-water slurry, as recommended, with those kept at room temperature increased the rate of diagnosis of GDM by 2.7-fold, entirely due to control of glycolysis.

“For example, comparison of glucose measured in samples collected in sodium fluoride-containing tubes kept in an ice-water slurry, as recommended (109), with those kept at room temperature increased the rate of diagnosis of GDM by 2.7-fold (277), entirely due to control of glycolysis.”

• cites [109] American Diabetes Association, 2011, Standards of medical care in diabetes—2011, Diabetes Care sourceCould not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [277] Daly, 2016, Impact of implementing preanalytical laboratory standards on the diagnosis of gestational diabetes Mmellitus: a prospective observational study, Clin Chem sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

• AssumptionRests on an assumption: The diagnosis of gestational diabetes mellitus is totally dependent on accurate measurement of glucose.

In 121 women screened for GDM with OGTTs, collecting samples in tubes containing citrate buffer doubled the diagnostic sensitivity for GDM compared with samples collected in sodium fluoride-containing tubes.

“Similarly, in 121 women screened for GDM with OGTTs, collecting samples in tubes containing citrate buffer doubled the diagnostic sensitivity for GDM compared with samples collected in sodium fluoridecontaining tubes (73).”

• cites [73] Daly, 2016, Comparison of citrate-fluoride-EDTA with fluoride-EDTA additives to stabilize plasma glucose measurements in women being screened during pregnancy with an oral glucose tolerance test: a prospective observational study, Clin Chem sourceSupported

• AssumptionRests on an assumption: The diagnosis of gestational diabetes mellitus is totally dependent on accurate measurement of glucose.

Women with GDM have a considerably increased risk of developing type 2 diabetes after pregnancy.

“In addition, women with GDM have a considerably increased risk of developing type 2 diabetes after pregnancy (273), and the Diabetes Prevention Program (DPP) found that progression to diabetes can be delayed or prevented by intervention (274); thus, long-term follow-up is important.”

• cites [273] Vounzoulaki, 2020, Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis, BMJ sourceSupported

The HAPO Follow Up Study results clearly demonstrate that maternal glycemia is associated with immediate and long-term adverse outcomes for both mother and offspring.

“The results clearly demonstrate that maternal glycemia is associated with immediate and long-term adverse outcomes for both mother and offspring.”

• cites [268] Lowe, 2018, Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity, JAMA sourcePartly supported

  The Abstract (page unavailable) says the original HAPO Study linked pregnancy glucose levels to perinatal outcomes, while the follow-up examined long-term outcomes in mothers and children. The Discussion (page unavailable) reports a long-term association with maternal glucose disorders and some childhood adiposity measures, but says the association with childhood overweight or obesity was not statistically significant. The claim overstates these findings by saying the follow-up results clearly demonstrate immediate and long-term adverse outcomes for both mother and offspring. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [269] Lowe, 2019, Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism, Diabetes Care sourcePartly supported

  The Conclusions report that maternal hyperglycemia during pregnancy was associated with a higher risk of impaired glucose tolerance in offspring at ages 10–14. They also mention a higher later risk of type 2 diabetes in mothers with GDM, but this study does not demonstrate immediate adverse outcomes for both mother and offspring. The claim therefore extends beyond what its results establish. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Semiquantitative urine glucose monitoring does not accurately reflect plasma glucose concentration.

“Semiquantitative urine glucose monitoring does not accurately reflect plasma glucose concentration (295).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourceSupported

Acetoacetate and acetone may increase as beta-hydroxybutyrate falls during successful therapy of diabetic ketoacidosis.

“since AcAc and acetone may increase as bOHB falls during successful therapy (295,298).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourcePartly supported

  The Urine ketone testing section says the relative proportions of β-hydroxybutyrate, acetoacetate, and acetone vary, and that urine ketones can persist during recovery from ketoacidosis after blood ketones fall. It does not say that acetoacetate and acetone may increase specifically as β-hydroxybutyrate falls during successful therapy; no page number is available in our copy. (LLM, conf=0.77)

  Experimental — accuracy not yet measured
• cites [298] Dhatariya, 2020, Diabetic ketoacidosis, Nat Rev Dis Primers sourcePartly supported

  The Diagnosis section (page unavailable) says β-hydroxybutyrate should decrease following fluid and intravenous insulin treatment. It discusses acetoacetate testing but does not say acetoacetate increases during successful therapy, and the searched passages do not report an increase in acetone. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

The nitroprusside reagent does not measure beta-hydroxybutyrate.

“Importantly, this reagent does not measure bOHB (295,304).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourceSupported
• cites [304] Sacks, 2023, Diabetes mellitusNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

In a large Chinese cohort, many women with FPG in the first trimester above the IADPSG threshold for GDM did not have GDM when tested later in gestation.

“For example, in a large Chinese cohort, many women with FPG in the first trimester above the IADPSG threshold for GDM did not have GDM when tested later in gestation (279).”

• cites [279] Zhu, 2013, Evaluation of the value of fasting plasma glucose in the first prenatal visit to diagnose gestational diabetes mellitus in China, Diabetes Care sourcePartly supported

  The Results report that only 39.8% of women with FPG ≥5.10 mmol/L at the first prenatal visit were diagnosed with GDM at 24–28 weeks, supporting the main point. But the paper does not restrict those first-visit measurements to the first trimester; its Conclusions explicitly distinguish “first prenatal visit” from “early pregnancy” because visit timing varied. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Beta-hydroxybutyrate is the predominant ketone body in diabetic ketoacidosis.

“bOHB, the predominant ketone body in DKA, is not detected.”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourceSupported
• cites [298] Dhatariya, 2020, Diabetic ketoacidosis, Nat Rev Dis Primers sourceSupported

One small study in children with diabetic ketoacidosis found that use of a point-of-care assay for beta-hydroxybutyrate decreased time to conversion from intravenous to subcutaneous insulin.

“One small study in children with DKA found that use of a POC assay for bOHB decreased time to conversion from intravenous to subcutaneous insulin.”

• cites [308] Noyes, 2007, Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children, Pediatr Diabetes sourcePartly supported

  In 'During treatment' (page not available), the proposed point-of-care hydroxybutyrate end-point was reached a median of 11 hours before the urine-ketone end-point in 28 pediatric DKA episodes. But the study states that hydroxybutyrate results did not inform clinical decisions; it therefore shows a potential for earlier conversion, not that using the assay actually decreased time to conversion. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The glycemic thresholds for the diagnosis of GDM in the second and third trimesters may not be appropriate for early pregnancy because FPG normally declines in early pregnancy.

“The glycemic thresholds for the diagnosis of GDM in the second and third trimesters may not be appropriate for early pregnancy because FPG normally declines in early pregnancy (282,283).”

• cites [282] Wei, 2019, Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index, Chin Med J (Engl) sourceSupported
• cites [283] Mills, 1998, Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study, Metabolism sourceNot checked — no full text of the source

Other studies suggest that biomarkers such as CD59 or serum secreted frizzle-related protein-5 may be useful in early identification of women in whom GDM will be identified later in pregnancy.

“Other studies suggest that biomarkers such as CD59 (287) or serum secreted frizzlerelated protein-5 (288) may be useful in early identification of women in whom GDM will be identified later in pregnancy.”

• cites [287] Ghosh, 2017, Plasma glycated CD59, a novel biomarker for detection of pregnancy-induced glucose intolerance, Diabetes Care sourcePartly supported

  The Results and Conclusions report that plasma glycated CD59 distinguished women with GDM and could be useful for screening. But the Research Design and Methods say samples were collected during routine screening at about 26 weeks, and the Conclusions identify detection earlier in pregnancy as a question for future studies. This paper therefore does not establish early identification of women whose GDM would be identified later in pregnancy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [288] Oztas, 2016, Prediction of gestational diabetes mellitus by first trimester serum secreted frizzle-related protein-5 levels, J Matern Fetal Neonatal Med sourceNot checked — no full text of the source

False-positive urine ketone results have been reported with highly colored urine and in the presence of several sulfhydryl-containing drugs, including angiotensin-converting enzyme inhibitors.

“False-positive results have been reported with highly colored urine and in the presence of several sulfhydrylcontaining drugs, including angiotensinconverting enzyme inhibitors (301).”

• cites [301] Brooke, 2016, Evaluation of the accuracy of capillary hydroxybutyrate measurement compared with other measurements in the diagnosis of diabetic ketoacidosis: a systematic review, Int J Environ Res Public Health sourcePartly supported

  The Discussion (section 7; page not provided) says sulphydryl drugs such as captopril could cause false-positive urine ketone results. It does not identify highly colored urine as a cause or explicitly describe captopril as an angiotensin-converting enzyme inhibitor. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Assay methods for ketones that do not include measurement of βOHB may provide misleading clinical information by underestimating total ketone body concentration.

“Thus, assay methods for ketones that do not include measurement of bOHB may provide misleading clinical information by underestimating total ketone body concentration (295,299).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourceSupported
• cites [299] Kilpatrick, 2022, Controversies around the measurement of blood ketones to diagnose and manage diabetic ketoacidosis, Diabetes Care sourceSupported

Concentrations of fructosamine and glycated albumin reflect mean glycemia over a shorter time (15 to 30 days) than glycated hemoglobin (60 to 90 days).

“Concentrations of these glycated proteins also reflect mean glycemia but over a much shorter time (15 to 30 days, reflecting the turnover of albumin) than GHb ( 60 to 90 days) (295,(311)(312)(313)(314)(315)(316).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourcePartly supported

  The “Glycated serum proteins” section says that albumin’s shorter turnover makes glycated serum proteins an index of glycemia over a shorter period than glycated hemoglobin. It does not give the claimed 15–30-day and 60–90-day windows; the “Glycated hemoglobin testing” section instead describes GHb as providing a glycemic history of the previous 120 days. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [311] Bunn, 1981, Nonenzymatic glycosylation of protein: relevance to diabetes, Am J Med sourceNot checked — no full text of the source
• cites [312] Goldstein, 1986, Glycated hemoglobin: methodologies and clinical applications, Clin ChemNot checked yet

  Not checked in the free run.

Individuals with well-documented diabetic ketoacidosis generally have beta-hydroxybutyrate concentrations greater than 2 mmol/L.

“Individuals with well-documented diabetic ketoacidosis (serum bicarbonate <15 mmol/L, arterial pH <7.3, plasma glucose >14.9 mmol/L [250 mg/dL]) generally have bOHB concentrations >2 mmol/L (299).”

• cites [299] Kilpatrick, 2022, Controversies around the measurement of blood ketones to diagnose and manage diabetic ketoacidosis, Diabetes Care sourceSupported

Hospitalization rates for diabetic ketoacidosis are increasing.

“Since hospitalization rates for DKA are increasing (310), further studies are needed to determine more optimal home testing strategies to detect impending ketonemia.”

• cites [310] Benoit, 2020, Trends in emergency department visits and inpatient admissions for hyperglycemic crises in adults with diabetes in the U.S., 2006–2015, Diabetes Care sourceSupported

Careful phenotyping of subjects with oral glucose tolerance testing supports an increase in HbA1c with age, even after removing those with otherwise undiagnosed diabetes and people with impaired glucose tolerance.

“Careful phenotyping of subjects with OGTT supports an increase in HbA 1c with age, even after removing those with otherwise undiagnosed diabetes and people with impaired glucose tolerance from the study population (336).”

• cites [336] Selvin, 2010, Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults, N Engl J Med sourceCould not verify

  The Methods describe fasting-glucose measurements and analyses of diabetes and cardiovascular risk, not phenotyping by oral glucose tolerance test (OGTT). Neither the Results nor the additional passages found for age and impaired glucose tolerance report whether HbA1c rises with age after excluding those groups. The claim cannot be verified from our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Population data show age-related increases in mean HbA1c in people without diabetes of approximately 0.1% per decade after age 30 years.

“Population data show age-related increases in mean HbA 1c in people without diabetes of approximately 0.1% per decade after age 30 years (334,335).”

• cites [334] Pani, 2008, Effect of aging on A1c levels in individuals without diabetes: evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001-2004, Diabetes Care sourceSupported
• cites [335] Ziemer, 2010, Glucose-independent, black-white differences in hemoglobin A1c levels: a cross-sectional analysis of 2 studies, Ann Intern Med sourceNot checked — no full text of the source

Few published studies have convincingly demonstrated a relationship between glycated protein levels and the chronic complications of diabetes.

“Few published studies have convincingly demonstrated a relationship between glycated protein levels and the chronic complications of diabetes (317).”

• cites [317] Nathan, 2014, Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study, Diabetes sourcePartly supported

  The Introduction (page unavailable) cites studies associating fructosamine or glycated albumin with long-term complications, and the Discussion reports an association between glycated albumin and microvascular complications. The paper does not say that few published studies have convincingly demonstrated such relationships; it also describes the HbA1c–complications relationship as well established. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Several technical advantages of HbA1c testing compared with glucose testing, such as its preanalytic stability and decreased biological variability, played a role in its adoption for diagnosis.

“Several technical advantages of HbA 1c testing compared with glucose testing, such as its preanalytic stability and decreased biological variability (318), also played a role.”

• cites [318] Sacks, 2011, A1c versus glucose testing: a comparison, Diabetes Care sourceSupported

A meta-analysis published in 2017 revealed continuing problems with the accuracy of point-of-care testing devices for HbA1c.

“A meta-analysis published in 2017 revealed continuing problems with the accuracy of POCT devices (324).”

• cites [324] Hirst, 2017, Performance of point-of-care HbA1c test devices: implications for use in clinical practice—a systematic review and meta-analysis, Clin Chem Lab Med sourceSupported

The introduction of continuous glucose monitoring devices that alarm with low blood glucose concentrations and semiautomated pumps that suspend insulin infusion as glucose concentrations decrease have facilitated achieving target HbA1c levels with less risk for hypoglycemia.

“Moreover, the introduction of CGM devices that alarm with low blood glucose concentrations and semiautomated pumps that suspend insulin infusion as glucose concentrations decrease have facilitated achieving target HbA 1c levels with less risk for hypoglycemia (332).”

• cites [332] Brown, 2019, Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes, N Engl J Med sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Sample stability is assay-method-specific.

“Sample stability is assay methodspecific (351,352).”

• cites [351] Rohlfing, 2012, Effects of whole blood storage on hemoglobin a1c measurements with five current assay methods, Diabetes Technol Ther sourceSupported
• cites [352] Little, 2007, Effects of sample storage conditions on glycated hemoglobin measurement: evaluation of five different high performance liquid chromatography methods, Diabetes Technol Ther sourceNot checked — no full text of the source

Any condition that shortens red blood cell survival or decreases mean red blood cell age falsely lowers HbA1c test results, compared with mean glycemia, regardless of the assay method.

“Any condition that shortens RBC survival or decreases mean RBC age (e.g., recovery from acute blood loss, hemolytic anemia) falsely lowers HbA 1c test results, compared with mean glycemia, regardless of the assay method (295).”

• cites [295] Goldstein, 2004, Tests of glycemia in diabetes, Diabetes Care sourceSupported

Several hemoglobin variants and chemically modified derivatives of hemoglobin interfere with some assay methods.

“Several hemoglobin variants (e.g., hemoglobins S, C, D, and E) and chemically modified derivatives of hemoglobin interfere with some assay methods (independent of any effects due to shortened RBC survival) (348-350) (for a review, see reference 347).”

• cites [348] Schnedl, 2000, Evaluation of Hb1c determination methods in patients with hemoglobinopathies, Diabetes Care sourcePartly supported

  The Conclusions (section labeled “Schnedl and Associates”; page not provided) state that hemoglobin variants interfere with HbA1c methods, and the paper reports method-dependent results for Hb S and Hb D. Our copy does not establish interference from chemically modified hemoglobin derivatives or the cited examples Hb C and Hb E. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [349] Rohlfing, 2021, Evaluation of interference from hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by fifteen methods, Clin Chim Acta sourcePartly supported

  The Introduction identifies method-specific interference from hemoglobin S, C, D, and E traits, and the Results report clinically significant interference for some assays. The paper does not address interference from chemically modified hemoglobin derivatives. Page numbers are not available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [350] Little, 2015, Effects of 49 different rare HhHb variants on HbA1c measurement in eight methods, J Diabetes Sci Technol sourcePartly supported

  The Abstract and Conclusions report that hemoglobin variants can interfere with some HbA1c assay methods, including analytical interference distinct from effects of shortened red-cell survival. Our copy does not report that chemically modified hemoglobin derivatives interfere with those methods; they appear only in a cited reference’s title. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The accuracy of capillary blood collection systems has been validated in several large research cohorts.

“The accuracy of such collection methods has been validated in several large research cohorts (353,354).”

• cites [353] Beck, 2021, An evaluation of two capillary sample collection kits for laboratory measurement of HbA1c, Diabetes Technol Ther sourceNot checked — no full text of the source
• cites [354] Nathan, 2021, Comparison of central laboratory HbA1c measurements obtained from a capillary collection versus a standard venous whole blood collection in the GRADE and EDIC studies, PLoS One sourceSupported

An analysis of 11,092 adults showed that Black individuals had mean HbA1c values 0.4% higher than White individuals.

“An analysis of 11,092 adults showed that Black individuals had mean HbA 1c values 0.4% higher than White individuals (336).”

• cites [336] Selvin, 2010, Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults, N Engl J Med sourceSupported

Since initiation of the NGSP in 1996, the College of American Pathologists proficiency testing survey has documented a steady improvement in comparability of glycated hemoglobin values among laboratories, both within method and between method.

“Since initiation of the NGSP in 1996, the College of American Pathologists proficiency testing survey has documented a steady improvement in comparability of GHb values among laboratories, both within method and between method (357,358,361).”

• cites [357] Little, 2019, The national glycohemoglobin standardization program: over 20 years of improving hemoglobin A1c measurement, Clin Chem sourceSupported
• cites [358] Little, 2001, The national glycohemoglobin standardization program: a five-year progress report, Clin ChemNot checked — no full text of the source
• cites [361] Little, 2011, Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care, Clin Chem sourceNot checked — no full text of the source

Race did not modify the association between the HbA1c concentration and adverse cardiovascular outcomes or death.

“However, race did not modify the association between the HbA 1c concentration and adverse cardiovascular outcomes or death (336).”

• cites [336] Selvin, 2010, Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults, N Engl J Med sourceSupported

Several studies have suggested a relatively higher HbA1c in Black and Hispanic populations than in White populations at the same level of glycemia.

“Several studies have suggested a relatively higher HbA 1c in Black and Hispanic populations than in White populations at the same level of glycemia, although glucose levels have not always been measured comprehensively to be confident that they capture true average glycemia (335,338,339).”

• cites [335] Ziemer, 2010, Glucose-independent, black-white differences in hemoglobin A1c levels: a cross-sectional analysis of 2 studies, Ann Intern Med sourceNot checked — no full text of the source
• cites [338] Herman, 2007, Differences in A1c by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program, Diabetes Care sourceSupported
• cites [339] Saaddine, 2002, Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey, Diabetes Care sourcePartly supported

  The Statistical analysis (p. 3) reports higher HbA1c in both non-Hispanic Black and Mexican-American youths than in White youths, but its fasting-glucose-adjusted result establishes the difference only for Black youths. The discussion (p. 4) cautions that the differences could reflect higher average glycemia, so the paper does not establish higher HbA1c for both groups at the same true average glycemia. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The consistency of glycemic measurements within races and the similar relationship of each glycemic measurement with complications in Black compared with White populations suggests that higher HbA1c measurements in Black populations reflects, at least in part, higher glycemic exposure and not just a difference in the relationship between mean glycemia and HbA1c levels.

“The consistency of glycemic measurements within races and the similar relationship of each glycemic measurement with complications in Black compared with White populations suggests that higher HbA 1c measurements in Black populations reflects, at least in part, higher glycemic exposure and not just a difference in the relationship between mean glycemia and HbA 1c levels.”

• cites [340] Parrinello, 2016, Racial differences in and prognostic value of biomarkers of hyperglycemia, Diabetes Care sourceSupported

There is some evidence that immediate feedback of HbA1c test results to patients at the time of the clinic visit improves long-term glycemic control.

“There is some evidence to suggest that immediate feedback of HbA 1c test results to patients at the time of the clinic visit improves long-term glycemic control (369,370).”

• cites [369] Cagliero, 1999, Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients, Diabetes Care sourceNot checked — no full text of the source
• cites [370] Kennedy, 2006, Impact of active versus usual algorithmic titration of basal insulin and point-of-care versus laboratory measurement of HbA1c on glycemic control in patients with type 2 diabetes: the glycemic optimization with algorithms and labs at point of care (GOAL A1c) trial, Diabetes Care sourcePartly supported

  The Secondary outcomes section reports that point-of-care A1C testing increased the proportion reaching the A1C target in a subgroup with baseline A1C above 10%. But the discussion says immediate results generally added no glycemic benefit beyond active insulin titration. The study measured outcomes over six months, so it does not establish a general improvement in long-term control. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

HLA-DR-DQ typing can be used only to increase or decrease the probability of type 1 diabetes.

“Thus, HLA-DR-DQ typing can be used only to increase or decrease the probability of type 1 diabetes and cannot be recommended for routine clinical diagnosis or classification (388).”

• cites [388] Sharp, 2019, Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis, Diabetes Care sourcePartly supported

  The Introduction (page not provided) describes HLA DR-DQ haplotypes as important factors that increase or decrease type 1 diabetes risk, supporting the probability-related part of the claim. The paper does not say that HLA-DR-DQ typing is limited to that use or recommend against its routine use for clinical diagnosis or classification. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Capillary blood sample kits have been used in research studies and shown to perform well compared with venous whole-blood samples when assayed with a high-performance chromatography method.

“Capillary blood sample kits have been used in research studies and shown to perform well compared with venous whole-blood samples when assayed with a high-performance chromatography method (353,354).”

• cites [353] Beck, 2021, An evaluation of two capillary sample collection kits for laboratory measurement of HbA1c, Diabetes Technol Ther sourceNot checked — no full text of the source
• cites [354] Nathan, 2021, Comparison of central laboratory HbA1c measurements obtained from a capillary collection versus a standard venous whole blood collection in the GRADE and EDIC studies, PLoS One sourceSupported

Non-HLA genetic factors include the genes for insulin (INS), PTPN22, CTLA-4, and several others.

“Non-HLA genetic factors include the genes for insulin (INS), PTPN22, CTLA-4, and several others (386,387).”

• cites [386] Barrett, 2009, Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes, Nat Genet sourceSupported
• cites [387] Concannon, 2009, Genetics of type 1A diabetes, N Engl J Med sourceNot checked — no full text of the source

The equation generated by the ADAG study is generally considered the most reliable one to date.

“The equation generated by the ADAG study is generally considered the most reliable one to date (341).”

• cites [341] Nathan, 2008, Translating the A1c assay into estimated average glucose values, Diabetes Care sourcePartly supported

  The Conclusions describe the ADAG equation as based on more complete glucose measurements than earlier studies and report less scatter than the widely used DCCT equation. They do not establish that it is generally considered the most reliable equation to date. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Several studies have demonstrated a close mathematical relationship between HbA1c concentration and mean glycemia that should allow expression of HbA1c as eAG.

“Several studies have demonstrated a close mathematical relationship between the HbA 1c concentration and mean glycemia that should allow expression of HbA 1c as an eAG (341,373,374).”

• cites [341] Nathan, 2008, Translating the A1c assay into estimated average glucose values, Diabetes Care sourceSupported
• cites [373] Murata, 2004, Contributions of weekly mean blood glucose values to hemoglobin A1c in insulin-treated type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES), Am J Med Sci sourceNot checked — no full text of the source
• cites [374] Nathan, 2007, Relationship between glycated haemoglobin levels and mean glucose levels over time, Diabetologia sourceSupported

Genome-wide association studies have confirmed a number of non-HLA genetic factors that increase the risk of a first appearing b-cell autoantibody or type 1 diabetes, both in first degree relatives of individuals with type 1 diabetes and in the general population.

“Genome-wide association studies have confirmed a number of non-HLA genetic factors that increase the risk of a first appearing b-cell autoantibody or type 1 diabetes, both in first degree relatives of individuals with type 1 diabetes and in the general population (386,387,404,405).”

• cites [386] Barrett, 2009, Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes, Nat Genet sourcePartly supported

  The Abstract (page not supplied) reports associations between multiple non-HLA loci and type 1 diabetes, tested in case-control samples and affected sib-pair families. It does not report risk of a first-appearing beta-cell autoantibody, and the affected sib-pair families do not establish the claimed finding in first-degree relatives generally. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [387] Concannon, 2009, Genetics of type 1A diabetes, N Engl J Med sourceNot checked — no full text of the source
• cites [404] Wellcome Trust Case Control Consortium, 2007, Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls, Nature sourcePartly supported

  The Type 1 diabetes (T1D) section reports associations between several non-HLA regions and T1D susceptibility, including findings confirmed in independent populations. It does not report risk of a first-appearing beta-cell autoantibody or assess these associations specifically in first-degree relatives of people with T1D. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [405] Todd, 2007, Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes, Nat Genet sourcePartly supported

  The Abstract reports confirmed associations between non-HLA chromosome regions and type 1 diabetes in independent cases and controls and in parent–child trios. It does not report whether these factors increase the risk of a first-appearing β-cell autoantibody, so that part of the citing sentence is unsupported by this paper. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Infants with neonatal diabetes due to a mutation in the KCNJ11 (Kir6.2) gene may be treated with a sulfonylurea rather than with insulin.

“For example, infants with neonatal diabetes due to a mutation in the KCNJ11 (Kir6.2) gene may be treated with a sulfonylurea rather than with insulin (382,384,398).”

• cites [382] Støy, 2008, Diagnosis and treatment of neonatal diabetes: a United States experience, Pediatr Diabetes sourceSupported
• cites [384] Carlsson, 2020, Absence of islet autoantibodies and modestly raised glucose values at diabetes diagnosis should lead to testing for MODY: lessons from a 5-year pediatric Swedish National Cohort Study, Diabetes Care sourceCould not verify

  The Introduction and Results discuss sulphonylurea treatment for HNF1A and HNF4A MODY, not KCNJ11-related neonatal diabetes. Searches for KCNJ11/Kir6.2 and neonatal diabetes found no passage in our copy addressing whether affected infants can use a sulfonylurea instead of insulin. (LLM, conf=0.77)

  Experimental — accuracy not yet measured
• cites [398] Pipatpolkai, 2020, New insights into KATP channel gene mutations and neonatal diabetes mellitus, Nat Rev Endocrinol sourceSupported

Autoantibody markers are usually present in 85% to 90% of individuals with type 1 diabetes when fasting hyperglycemia is initially detected.

“Autoantibody markers are usually present in 85% to 90% of individuals with type 1 diabetes when fasting hyperglycemia is initially detected (2).”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourcePartly supported

  The Diagnosis section says that stage 1 type 1 diabetes is defined by two or more autoimmune markers, supporting their role in the disease. Our copy does not give an 85%–90% prevalence or tie that figure to the initial detection of fasting hyperglycemia; searches for those terms found no matching passage. Page numbers were not provided. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

A genetic risk score may be used at birth to identify children with a particularly high genetic risk of development of islet autoimmunity or type 1 diabetes.

“A genetic risk score may be used at birth to identify children with a particularly high genetic risk of development of islet autoimmunity or type 1 diabetes (388,390,392).”

• cites [388] Sharp, 2019, Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis, Diabetes Care sourceSupported
• cites [390] Ferrat, 2020, A combined risk score enhances prediction of type 1 diabetes among susceptible children, Nat Med sourceSupported
• cites [392] Bonifacio, 2018, Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: a prospective study in children, PLoS Med sourceSupported

The risk of type 1 diabetes in the general population may be determined by HLA-DQ typing, which contribute as much as 50% of familial susceptibility.

“The risk of type 1 diabetes in the general population may be determined by HLA-DQ typing, which contribute as much as 50% of familial susceptibility (400).”

• cites [400] Redondo, 2018, Genetics of type 1 diabetes, Pediatr Diabetes sourcePartly supported

  The HLA region section says the HLA region accounts for approximately 50% of familial aggregation of type 1 diabetes, with the strongest association at HLA-DR and HLA-DQ. The Genetic scores section discusses HLA-DR/DQ genotyping for risk prediction in children from the general population. The paper does not assign the full 50% contribution to HLA-DQ alone or say that HLA-DQ typing by itself determines risk. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

In individuals who are islet autoantibody positive, HLA-DR-DQ genotyping or Genetic Risk Score analysis will help define the risk of type 1 diabetes.

“In those individuals who are islet autoantibody positive, HLA-DR-DQ genotyping or an analysis of Genetic Risk Score (388,392) will help define the risk of type 1 diabetes.”

• cites [388] Sharp, 2019, Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis, Diabetes Care sourcePartly supported

  The Introduction identifies HLA-DR-DQ as a major contributor to type 1 diabetes risk and says genetic risk scores improve risk discrimination. The Conclusions report that a model combining autoantibody data, a genetic risk score, age, and a metabolic score predicted progression in at-risk relatives. The paper does not establish that HLA-DR-DQ genotyping or a genetic risk score alone defines risk specifically among autoantibody-positive individuals. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [392] Bonifacio, 2018, Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: a prospective study in children, PLoS Med sourcePartly supported

  The Discussion (page unavailable) reports that genetic scores stratified the risk of developing islet autoantibodies and clinical type 1 diabetes in children with high-risk HLA genotypes. But the study assessed risk from infancy, before autoantibody development; it does not establish that HLA genotyping or a genetic risk score defines diabetes risk specifically among people who are already islet-autoantibody positive. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The performance of GADA and IA-2A assays is improving, as demonstrated by the Islet Autoantibody Standardization Program.

“The performance of GADA and IA-2A assays is improving, as demonstrated by the Islet Autoantibody Standardization Program (440,442).”

• cites [440] Bonifacio, 2010, Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for National Institute of Diabetes and Digestive and Kidney Diseases consortia, J Clin Endocrinol Metab sourceNot checked — no full text of the source
• cites [442] Lampasona, 2019, Islet Autoantibody Standardization Program 2018 workshop: interlaboratory comparison of glutamic acid decarboxylase autoantibody assay performance, Clin Chem sourcePartly supported

  The Abstract Conclusions and Discussion report high-performing GADA assays, including nonradioactive formats that performed as well as or better than the previous gold-standard format. But this 2018 comparison does not establish a trend of improvement over time, and it evaluates GADA assays, not IA-2A assays. No page numbers are provided in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Because of the low prevalence of type 1 diabetes (approximately 0.3% in the general population), the positive predictive value of a single islet autoantibody is low.

“Because of the low prevalence of type 1 diabetes (approximately 0.3% in the general population), the positive predictive value of a single islet autoantibody is low (408).”

• cites [408] Ziegler, 2013, Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children, JAMA sourcePartly supported

  The Results report a 12.7% risk of diabetes by age 15 in children with one islet autoantibody, versus 61.6% with two, supporting the point that a single antibody is less predictive. The paper does not give a 0.3% general-population prevalence or attribute the lower predictive value to that prevalence. The Discussion also cautions that its genetically susceptible cohort may not represent the general population (page numbers unavailable). (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The CD3 monoclonal antibody teplizumab has been shown to delay progression to type 1 diabetes in high-risk individuals.

“The CD3 monoclonal antibody teplizumab has been shown to delay progression to type 1 diabetes in high-risk individuals (429).”

• cites [429] Herold, 2019, An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes, N Engl J Med sourceSupported

In islet cell or pancreas transplantation, the presence or absence of islet autoantibodies may indicate whether a subsequent failure of the transplanted islets is due to recurrent autoimmune disease or to rejection.

“In islet cell or pancreas transplantation, the presence or absence of islet autoantibodies may indicate whether a subsequent failure of the transplanted islets is due to recurrent autoimmune disease or to rejection (431).”

• cites [431] Braghi, 2000, Modulation of humoral islet autoimmunity by pancreas allotransplantation influences allograft outcome in patients with type 1 diabetes, Diabetes sourcePartly supported

  The conclusion (RESEARCH DESIGN AND METHODS > B A; page unavailable) says that rising islet autoantibodies after pancreas transplantation may identify graft failures caused by recurrent autoimmunity. The paper does not establish that absent antibodies indicate rejection, and its own study concerns pancreas rather than islet-cell transplants. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Approximately 10% of individuals presenting with new-onset diabetes express only a single autoantibody.

“approximately 10% of individuals presenting with new-onset diabetes express only a single autoantibody (445).”

• cites [445] Andersson, 2014, Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies, Pediatr Diabetes sourcePartly supported

  The Results section ('ICA positivity in children enrolled in the Better Diabetes Diagnosis Study'; page unavailable) reports a single autoantibody—ICA—in 17 of 229 children with type 1 diabetes who had tested negative for the other autoantibodies, or about 7%. That is a selected subgroup, not approximately 10% of all individuals presenting with new-onset diabetes; the paper does not give the claimed overall prevalence of exactly one autoantibody. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

At diagnosis of diabetes in children, absence of all four islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) proved useful for the detection of MODY.

“At diagnosis of diabetes in children, absence of all four islet autoantibodies and modest hyperglycemia (HbA 1c <7.5% [58 mmol/mol]) proved useful for the detection of MODY (384).”

• cites [384] Carlsson, 2020, Absence of islet autoantibodies and modestly raised glucose values at diabetes diagnosis should lead to testing for MODY: lessons from a 5-year pediatric Swedish National Cohort Study, Diabetes Care sourceSupported

High-risk individuals identified within such protocols are less likely to present in DKA.

“However, high-risk individuals identified within such protocols are less likely to present in DKA (430).”

• cites [430] Steck, 2017, Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls, Pediatr Diabetes sourceSupported

Only about 15% of individuals with newly diagnosed type 1 diabetes have a first-degree relative with the disease.

“Only about 15% of individuals with newly diagnosed type 1 diabetes have a first-degree relative with the disease (420).”

• cites [420] Patterson, 2009, Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study, Lancet sourceCould not verify

  The Abstract reports incidence trends and predicted numbers of new childhood type 1 diabetes cases in Europe, not family history. Searches for “first-degree,” “family history,” and “15%” found no passage in our copy stating what proportion of newly diagnosed people have an affected first-degree relative. (LLM, conf=0.77)

  Experimental — accuracy not yet measured

Older individuals (age >75 years) or with life expectancy <20 years are at moderately increased risk of cardiovascular mortality.

“they will be at moderately increased risk of cardiovascular mortality, with severity of chronic kidney disease (CKD) acting as a risk multiplier (458,459).”

• cites [458] Go, 2004, Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization, N Engl J Med sourcePartly supported

  The Outcomes According to the Estimated GFR section reports that cardiovascular-event risk rises as estimated GFR falls, supporting the CKD-severity part of the citing sentence. It measures death from any cause separately, not cardiovascular mortality, and does not establish the stated risk specifically for people over 75 or with life expectancy under 20 years. The Statistical Analysis section uses age categories but does not supply those claimed subgroup findings; page numbers are unavailable in our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [459] Beddhu, 2021, Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes, BMC Nephrol sourcePartly supported

  The Discussion reports that participants with CKD had a higher risk of cardiovascular events than those without CKD. It does not establish cardiovascular mortality risk specifically, quantify it as moderate, or show that risk rises with CKD severity. The Results table lists participants aged ≥75 but does not link that age group—or life expectancy under 20 years—to cardiovascular mortality. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

It is cost-effective to screen all people with diabetes and/or kidney disease for albuminuria.

“Published studies have also demonstrated that it is costeffective to screen all people with diabetes and/or kidney disease for albuminuria (461,462).”

• cites [461] Lepore, 2002, Cost-effectiveness of two screening programs for microalbuminuria in type 2 diabetes, Diabetes Care sourceNot checked — no full text of the source
• cites [462] Incerti, 2005, Evaluation of tests for microalbuminuria screening in patients with diabetes, Nephrol Dial Transplant sourcePartly supported

  The Cost of microalbuminuria diagnosis section compares per-patient costs of three screening tests in patients with diabetes, and the Discussion identifies the lowest-cost test. It does not establish that screening all people with diabetes is cost-effective, or assess screening people with kidney disease generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

The anti-CD3 monoclonal antibody teplizumab delays progression to type 1 diabetes in high-risk individuals.

“there is now evidence that the anti-CD3 monoclonal antibody teplizumab delays progression to type 1 diabetes in high-risk individuals (429).”

• cites [429] Herold, 2019, An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes, N Engl J Med sourceSupported

The FIGARO-DKD outcome trial demonstrates a significant relationship between reduction in moderately increased albuminuria and reduction in cardiovascular risk.

“The Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) outcome trial (460) demonstrates a significant relationship between reduction in moderately increased albuminuria and reduction in cardiovascular risk.”

• cites [460] Pitt, 2021, Cardiovascular events with finerenone in kidney disease and type 2 diabetes, N Engl J Med sourcePartly supported

  The Results report a significant reduction in cardiovascular events with finerenone, and Secondary and Exploratory Outcomes report a greater reduction in urinary albumin-to-creatinine ratio than with placebo. The paper does not demonstrate a significant relationship between the *reduction in albuminuria* and the *reduction in cardiovascular risk*; it reports them as separate outcomes. The trial also included patients with severely, as well as moderately, elevated albuminuria. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

SGLT2 inhibitors and finerenone reduce albuminuria in clinical trials of advanced diabetic kidney disease.

“SGLT2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, also reduce albuminuria in clinical trials of advanced diabetic kidney disease (471-473).”

• cites [471] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med sourcePartly supported

  The Effect on Intermediate Outcomes section reports that urinary albumin-to-creatinine ratio was 31% lower with canagliflozin, an SGLT2 inhibitor, than with placebo during follow-up. The Methods describe patients with type 2 diabetes and albuminuric chronic kidney disease, but the paper does not report a finerenone trial; it also says patients with very advanced kidney disease (estimated GFR below 30) were excluded. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [472] Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med sourcePartly supported

  The Participants and Discussion sections describe a clinical trial of dapagliflozin, an SGLT2 inhibitor, in people with chronic kidney disease, including those with type 2 diabetes. The reported benefit concerns kidney and cardiovascular outcomes; the paper does not report that dapagliflozin reduced albuminuria, and it does not address finerenone. (LLM, conf=0.81)

  Experimental — accuracy not yet measured
• cites [473] Bakris, 2020, Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes, N Engl J Med sourceSupported

Severity of chronic kidney disease acts as a risk multiplier for cardiovascular mortality.

“with severity of chronic kidney disease (CKD) acting as a risk multiplier (458,459).”

• cites [458] Go, 2004, Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization, N Engl J Med sourcePartly supported

  The Abstract reports a graded association between lower estimated GFR and higher risks of death and cardiovascular events. The outcomes section specifies that death was measured from any cause and cardiovascular events were defined by hospitalization, so these passages do not establish a graded increase in cardiovascular mortality specifically. The study reports an association, not a causal multiplier. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [459] Beddhu, 2021, Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes, BMC Nephrol sourcePartly supported

  The Results report that CKD was associated with a higher risk of cardiovascular events (HR 3.35), and the Methods define those events as a composite that includes cardiovascular death. The study compares CKD with non-CKD participants; it does not establish that increasing CKD severity multiplies the risk of cardiovascular mortality specifically. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Albuminuria is a continuous variable for cardiovascular risk.

“reinforcing the notion that albuminuria is a continuous variable for cardiovascular risk (466-468).”

• cites [466] Pambianco, 2007, The prediction of major outcomes of type 1 diabetes: a 12-year prospective evaluation of three separate definitions of the metabolic syndrome and their components and estimated glucose disposal rate: the Pittsburgh Epidemiology of Diabetes Complications Study experience, Diabetes Care sourcePartly supported

  The Results section concludes that microalbuminuria predicts cardiovascular risk in people with type 1 diabetes. The WHO definition section uses an albumin-excretion cutoff, however, and the paper does not establish that cardiovascular risk varies continuously with albuminuria levels or extend its finding beyond this population. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [467] Rachmani, 2000, Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus: lessons from an 8-year follow-up study of 599 patients, Diabetes Res Clin Pract sourceNot checked — no full text of the source
• cites [468] Wachtell, 2003, Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study, Ann Intern Med sourceNot checked — no full text of the source

The uACR may be useful in determining the rate of progression of disease and thus support planning for care of end-stage renal disease using the Kidney Failure Risk Equation.

“The uACR may also be useful in determining the rate of progression of disease and thus support planning for care of end-stage renal disease using the Kidney Failure Risk Equation (474).”

• cites [474] Tangri, 2016, Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis, JAMA sourceSupported

Older individuals (age >75 years) or with life expectancy <20 years may not be at increased risk of kidney failure requiring replacement therapy during their lifetimes.

“While older individuals (age >75 years) or with life expectancy <20 years may not be at increased risk of kidney failure requiring replacement therapy during their lifetimes”

• cites [458] Go, 2004, Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization, N Engl J Med sourceCould not verify

  The Outcomes According to the Estimated GFR section reports how many participants began dialysis or underwent transplantation during a median 2.84-year follow-up. Neither that section nor the other passages located by searches for age over 75 and life expectancy under 20 years assesses whether those groups are at increased risk of kidney failure requiring replacement therapy during their lifetimes. (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites [459] Beddhu, 2021, Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes, BMC Nephrol sourceCould not verify

  The Results report participants’ ages, including the proportion aged 75 or older, while the Background and Discussion address cardiovascular events and carotid plaque in CKD. Searches for kidney failure requiring replacement therapy and for the stated age and life-expectancy thresholds found no passage assessing lifetime risk of kidney failure. (LLM, conf=0.74)

  Experimental — accuracy not yet measured

Most longitudinal cohort studies report significant increases in the prevalence of moderately increased albuminuria only after type 1 diabetes has been present for 5 years.

“Most longitudinal cohort studies report significant increases in the prevalence of moderately increased albuminuria only after type 1 diabetes has been present for 5 years (456,457).”

• cites [456] KDOQI, 2007, KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease, Am J Kidney Dis sourceSupported
• cites [457] Vassalotti, 2007, Testing for chronic kidney disease: a position statement from the National Kidney Foundation, Am J Kidney Dis sourceNot checked — no full text of the source

Cardiovascular risk may extend below the lower limit of 30 mg/day of albuminuria.

“Moreover, cardiovascular risk may extend below the lower limit of 30 mg/day (463-465)”

• cites [463] Klausen, 2006, Very low level of microalbuminuria is associated with increased risk of death in subjects with cardiovascular or cerebrovascular diseases, J Intern Med sourceNot checked — no full text of the source
• cites [464] Klausen, 2005, New definition of microalbuminuria in hypertensive subjects: association with incident coronary heart disease and death, Hypertension sourceNot checked — no full text of the source
• cites [465] Ratto, 2006, Microalbuminuria and cardiovascular risk assessment in primary hypertension: should threshold levels be revised?, Am J Hypertens sourceSupported

Mean biases of urine albumin measurement procedures were large and ranged from -35% to 34% at 15 mg/L.

“Mean biases were large and ranged from À35% to 34% at 15 mg/L.”

• cites [498] Bachmann, 2014, State of the art for measurement of urine albumin: comparison of routine measurement procedures to isotope dilution tandem mass spectrometry, Clin Chem sourceSupported

In multiple epidemiological studies, moderately increased albuminuria is an independent risk marker for cardiovascular death.

“In multiple epidemiological studies, moderately increased albuminuria is an independent risk marker for cardiovascular death (481-483).”

• cites [481] Levey, 2011, The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report, Kidney Int sourceNot checked — no full text of the source
• cites [482] Kistorp, 2005, N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults, JAMA sourcePartly supported

  The Comment section (page unavailable) describes urinary albumin excretion as a well-known risk marker and says this study found it independently predicted death and a first major cardiovascular event. The Mortality and Cardiovascular Events sections report all-cause death and a composite cardiovascular outcome, respectively; they do not establish an independent association specifically with cardiovascular death. The passages also do not identify the studied levels as moderately increased albuminuria. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [483] Yuyun, 2004, Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population: The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study, Int J Epidemiol sourceNot checked — no full text of the source

Others have validated the reliability of a first morning void sample.

“Others have validated the reliability of a first morning void sample (462,492, 493).”

• cites [462] Incerti, 2005, Evaluation of tests for microalbuminuria screening in patients with diabetes, Nephrol Dial Transplant sourcePartly supported

  The Discussion reports that albumin measurements from first-morning urine correlate more closely with 24-hour protein excretion than measurements from random spot samples. However, the study itself tested random spot samples, not first-morning voids, so it reports evidence for their reliability rather than independently validating them. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [492] Gansevoort, 2005, The validity of screening based on spot morning urine samples to detect subjects with microalbuminuria in the general population, Kidney Int Suppl sourceNot checked — no full text of the source
• cites [493] Meinhardt, 2003, Microalbuminuria in diabetes mellitus: efficacy of a new screening method in comparison with timed overnight urine collection, J Diabetes Complications sourceNot checked — no full text of the source

Approximately 20% of people with diabetes progress to end-stage kidney disease without an increase in moderately increased albuminuria.

“Moreover, approximately 20% of people with diabetes progress to end-stage kidney disease without an increase in moderately increased albuminuria (488).”

• cites [488] Steinke, 2005, The early natural history of nephropathy in type 1 diabetes: III. Predictors of 5–year urinary albumin excretion rate patterns in initially normoalbuminuric patients, Diabetes sourceCould not verify

  The introduction discusses ESRD risk and persistent microalbuminuria, while the Discussion describes kidney injury that can precede albuminuria. Neither section reports that approximately 20% of people with diabetes reach ESRD without an increase in albuminuria. Searches for that percentage and for progression to ESRD without microalbuminuria found no supporting passage. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

Cystatin C may detect kidney dysfunction at an earlier stage than creatinine in people with diabetes.

“Cystatin C may also detect kidney dysfunction at an earlier stage than creatinine in people with diabetes (480).”

• cites [480] Asmamaw, 2020, Early detection of renal impairment among patients with type 2 diabetes mellitus through evaluation of serum cystatin C in comparison with serum creatinine levels: a cross-sectional study, Diabetes Metab Syndr Obes sourceSupported

The albumin-to-creatinine ratio is the best method to predict renal events in people with type 2 diabetes.

“The albumin-to-creatinine ratio is the best method to predict renal events in people with type 2 diabetes (490).”

• cites [490] Lambers Heerspink, 2010, Comparison of different measures of urinary protein excretion for prediction of renal events, J Am Soc Nephrol sourcePartly supported

  The Abstract reports that the albumin-to-creatinine ratio from a first-morning void predicted renal events better than the other measures tested. However, the study examined patients with type 2 diabetes and nephropathy, not people with type 2 diabetes generally; the Discussion says its results cannot be directly applied to people without nephropathy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Adding cystatin C to serum creatinine improves the accuracy of race-neutral eGFR equations.

“Adding cystatin C to serum creatinine improves the accuracy of race-neutral eGFR equations (476,477)”

• cites [476] Inker, 2021, New creatinine- and cystatin C-based equations to estimate GFR without race, N Engl J Med sourceSupported
• cites [477] Inker, 2012, Estimating glomerular filtration rate from serum creatinine and cystatin C, N Engl J Med sourcePartly supported

  The Results (Performance of New Equations in the Validation Data Set; page unavailable) report that the creatinine–cystatin C equation was more accurate than the creatinine-only equation. But the Results (Formulation of Equations; page unavailable) say adding race improved the combined equation’s performance, so the paper does not establish the claimed accuracy improvement specifically for race-neutral equations. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Dipstick methods were compared with local laboratory methods, which exhibit large biases.

“An important limitation of all these data is that the dipstick methods were compared with local laboratory methods, which, as indicated above, exhibit large biases (498).”

• cites [498] Bachmann, 2014, State of the art for measurement of urine albumin: comparison of routine measurement procedures to isotope dilution tandem mass spectrometry, Clin Chem sourceSupported

Given sufficiently sensitive techniques, insulin antibodies can be detected in any person being treated with exogenous insulin.

“Given sufficiently sensitive techniques, insulin antibodies can be detected in any person being treated with exogenous insulin (518,519).”

• cites [518] Censi, 2018, Insulin autoimmune syndrome: from diagnosis to clinical management, Ann Transl Med sourcePartly supported

  The discussion of IAA related to other conditions (indexed as References; page not provided) says exogenous insulin may induce insulin-binding antibodies. It does not say antibodies are detectable in every person receiving exogenous insulin, even with sufficiently sensitive techniques. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [519] Hu, 2018, Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients, Endocr Connect sourcePartly supported

  The Introduction (page not specified) says exogenous insulin can induce insulin antibodies, including with human insulin. It does not say that sufficiently sensitive techniques can detect them in every person treated with exogenous insulin; it instead describes a reduced incidence with purified and recombinant preparations. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

In most individuals treated with exogenous insulin, the titer of insulin antibodies is low, particularly in those who were never treated with animal insulins.

“In most of these individuals, the titer of insulin antibodies is low, particularly in those who were never treated with animal insulins”

• cites [518] Censi, 2018, Insulin autoimmune syndrome: from diagnosis to clinical management, Ann Transl Med sourcePartly supported

  The passage on insulin antibodies related to other conditions (indexed under References; page unavailable) says antibodies induced by exogenous insulin are usually weak, broadly supporting the claim’s first part. It does not say their titers are low or that this is particularly true of people never treated with animal insulin. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [519] Hu, 2018, Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients, Endocr Connect sourceSupported

The presence of insulin antibodies is of no clinical significance in most individuals treated with exogenous insulin.

“and their presence is of no clinical significance.”

• cites [518] Censi, 2018, Insulin autoimmune syndrome: from diagnosis to clinical management, Ann Transl Med sourceSupported
• cites [519] Hu, 2018, Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients, Endocr Connect sourceSupported

Measurement of C-peptide can aid in instances in which it is difficult to differentiate between the diagnosis of type 1 and type 2 diabetes.

“Measurement of the C-peptide, in the fasting state or in response to intravenous glucagon, can aid in instances in which it is difficult to differentiate between the diagnosis of type 1 and type 2 diabetes (5,511).”

• cites [5] Sacks, 1996, The pathogenesis of type II diabetes mellitus. A polygenic disease, Am J Clin Pathol sourceCould not verify

  The Loss of β-Cell Function section discusses insulin responses to intravenous glucose and other secretagogues, but not C-peptide testing for distinguishing type 1 from type 2 diabetes. Searches for C-peptide and diagnostic differentiation found no passage addressing that use; the indexed passages provide no page number. (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites [511] Leighton, 2017, A practical review of C-peptide testing in diabetes, Diabetes Ther sourceSupported

Pooling results from a bivariate random-effects model gave sensitivity and specificity estimates of 76% and 93%, respectively, for the semiquantitative test.

“Pooling results from a bivariate randomeffects model gave sensitivity and specificity estimates of 76% (95% CI, 63-86%) and 93% (CI, 84-97%), respectively, for the semiquantitative test (501).”

• cites [501] Shin, 2021, Albuminuria testing in hypertension and diabetes: an individual-participant data meta-analysis in a global consortium, Hypertension sourceCould not verify

  The Methods (Statistical Analyses; page unavailable) describe logistic prediction models whose estimates were combined by random-effects meta-analysis, not a bivariate diagnostic-accuracy model. A search for the semiquantitative test and the stated sensitivity and specificity found no passage reporting the 76% and 93% estimates or their confidence intervals. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Population studies have shown that fasting insulin concentration predicts future risk of ischemic heart disease events.

“Population studies have shown that fasting insulin concentration predicts future risk of ischemic heart disease events (507).”

• cites [507] Després, 1996, Hyperinsulinemia as an independent risk factor for ischemic heart disease, N Engl J Med sourceSupported

A cost-effectiveness analysis concluded that the semiquantitative uACR dipstick method could be an appropriate screening tool for albuminuria in people with diabetes.

“A cost-effectiveness analysis of 1,881 individuals with diabetes published in 2020 evaluated medical costs of CKD and concluded that the semiquantitative uACR dipstick method could be an appropriate screening tool for albuminuria in people with diabetes.”

• cites [503] Kim, 2020, Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden, PLoS One sourceSupported

Earlier studies may not have controlled well for undiagnosed diabetes, glycemic measures, BMI, or other confounders.

“Earlier studies may not have controlled well for undiagnosed diabetes, glycemic measures, BMI, or other confounders (507).”

• cites [507] Després, 1996, Hyperinsulinemia as an independent risk factor for ischemic heart disease, N Engl J Med sourceCould not verify

  The Discussion (page unavailable) says previous prospective studies did not identify insulin as an independent predictor after adjustment for other risk factors, but it does not say their control of confounding was inadequate. Matching Procedures describes this study’s matching on BMI and exclusion of men with reported diabetes; no passage found assesses earlier studies’ handling of undiagnosed diabetes, glycemic measures, BMI, or other confounders. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

KCNJ11-related neonatal diabetes is characterized by intrauterine growth restriction (IUGR).

“IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

INS mutations cause permanent neonatal diabetes.

“Permanent: IUGR; insulin requiring”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

HNF1B-MODY is characterized by genitourinary abnormalities.

“genitourinary”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

ABCC8-related neonatal diabetes is responsive to sulfonylureas.

“responsive to sulfonylureas”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

High titers of insulin antibodies in the circulation can be associated with dramatic resistance to the ability of exogenous insulin to lower plasma glucose concentrations.

“However, on occasion high titers of insulin antibodies in the circulation can be associated with dramatic resistance to the ability of exogenous insulin to lower plasma glucose concentrations.”

• cites [519] Hu, 2018, Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients, Endocr Connect sourceSupported

INS-related neonatal diabetes is characterized by intrauterine growth restriction (IUGR).

“IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

KCNJ11-related neonatal diabetes is responsive to sulfonylureas.

“responsive to sulfonylureas”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

HNF1B-MODY is characterized by developmental renal disease, typically cystic.

“HNF1B-MODY: developmental renal disease”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

ABCC8 mutations cause permanent or transient neonatal diabetes.

“Permanent or transient: IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

ABCC8-related neonatal diabetes rarely has developmental delay.

“developmental delay”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

ABCC8-related neonatal diabetes is characterized by intrauterine growth restriction (IUGR).

“IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

INS-related neonatal diabetes is insulin requiring.

“insulin requiring”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

The cause-and-effect relationships between the magnitude of the increase in insulin antibodies and the degree of insulin resistance are unclear.

“and the cause-and-effect relationships between the magnitude of the increase in insulin antibodies and the degree of insulin resistance are unclear (519).”

• cites [519] Hu, 2018, Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients, Endocr Connect sourceSupported

KCNJ11-related neonatal diabetes may have developmental delay and seizures.

“developmental delay and seizures”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

KCNJ11 mutations cause permanent or transient neonatal diabetes.

“Permanent or transient: IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

HNF1B-MODY is characterized by gout.

“gout”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

GATA6-related neonatal diabetes is characterized by pancreatic exocrine insufficiency.

“pancreatic exocrine”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24-related transient neonatal diabetes is characterized by umbilical hernia.

“hernia”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

GATA6 mutations cause permanent neonatal diabetes.

“Permanent: pancreatic hypoplasia; cardiac”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

EIF2AK3 mutations cause permanent neonatal diabetes (Wolcott-Rallison syndrome).

“Permanent: Wolcott-Rallison syndrome”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24-related transient neonatal diabetes may be treatable with medications other than insulin.

“medications other than insulin”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

GATA6-related neonatal diabetes is insulin requiring.

“insulin requiring”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24 (PLAGL1, HYMA1) paternal duplications are inherited in an autosomal dominant manner.

“6q24 (PLAGL1, HYMA1) | AD for paternal duplications”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

GATA6-related neonatal diabetes is characterized by pancreatic hypoplasia.

“pancreatic hypoplasia”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

FOXP3 mutations cause permanent neonatal diabetes (IPEX syndrome).

“Permanent: immunodysregulation,”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

EIF2B1-related permanent diabetes can be associated with fluctuating liver function.

“fluctuating liver function”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

Wolcott-Rallison syndrome is characterized by pancreatic exocrine insufficiency.

“pancreatic exocrine”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24-related transient neonatal diabetes is characterized by macroglossia.

“macroglossia”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24-related transient neonatal diabetes is characterized by intrauterine growth restriction (IUGR).

“IUGR”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

EIF2B1 mutations cause permanent diabetes.

“Permanent diabetes”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

Wolcott-Rallison syndrome is insulin requiring.

“insulin requiring”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

6q24 (PLAGL1, HYMA1) paternal duplications cause transient neonatal diabetes.

“Transient: IUGR; macroglossia; umbilical”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

GATA6-related neonatal diabetes is characterized by cardiac malformations.

“cardiac”

• cites [2] American Diabetes Association Professional Practice Committee, 2021, 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2022, Diabetes Care sourceSupported

Associations between maternal glycemia and HAPO primary outcomes remained strong after adjustments for multiple, potentially confounding factors.

“Associations remained strong after adjustments for multiple, potentially confounding factors.”

• cites [248] Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med sourceNot checked — no full text of the source

Neonatal hypoglycemia (detected clinically or biochemically) was significantly associated with maternal glycemia.

“Neonatal hypoglycemia (detected clinically or biochemically) was also significantly associated with maternal glycemia (256).”

• cites [256] Metzger, 2010, Hyperglycemia and Adverse Pregnancy Outcome study: neonatal glycemia, Pediatrics sourceNot checked — no full text of the source

Variability is reported in the ratio between glucose concentrations in blood and tear fluid for individual rabbits.

“Variability is reported in the ratio between glucose concentrations in blood and tear fluid for individual rabbits (247).”

• cites [247] Yan, 2011, Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration, Anal Chem sourceNot checked — no full text of the source

In general, noninvasive glucose measurement systems from research-grade instruments or engineering prototypes lack the ability to provide accurate glucose concentration measurements after system calibration.

“In general, these systems lack the ability to provide accurate glucose concentration measurements after system calibration.”

HAPO revealed strong, graded, predominantly linear associations between maternal glycemia and primary study outcomes, namely frequency of birth weight >90th percentile, delivery by cesarean section, clinically identified neonatal hypoglycemia, and cord serum insulin (assessed by measuring C-peptide) concentrations >90th percentile of values in the HAPO study population.

“The study revealed strong, graded, predominantly linear associations between maternal glycemia and primary study outcomes, namely frequency of birth weight >90th percentile, delivery by cesarean section, clinically identified neonatal hypoglycemia, and cord serum insulin (assessed by measuring C-peptide) concentrations >90th percentile of values in the HAPO study population.”

• cites [248] Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med sourceNot checked — no full text of the source

Strong associations were also found between maternal glycemia and infant adiposity.

“Strong associations were also found with infant adiposity (248).”

• cites [248] Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med sourceNot checked — no full text of the source

Another study observed that the decision whether to add pharmacological therapy in GDM could be made with BGM every other or every third day instead of daily.

“Another study observed that the decision whether to add pharmacological therapy in GDM could be made with BGM every other or every third day instead of daily (271).”

• cites [271] Mendez-Figueroa, 2013, Comparing daily versus less frequent blood glucose monitoring in patients with mild gestational diabetes, J Matern Fetal Neonatal Med sourceNot checked — no full text of the source

One report found a lower frequency of large-for-gestational-age babies in GDM mothers who did BGM four times daily compared with a group with measurement of plasma glucose in the laboratory at the time of an office visit every 1 to 2 weeks.

“However, one report did find a lower frequency of large-for-gestational-age babies in GDM mothers who did BGM four times daily compared with a group with measurement of plasma glucose in the laboratory at the time of an office visit every 1 to 2 weeks (270).”

• cites [270] Hawkins, 2009, Weekly compared with daily blood glucose monitoring in women with diet-treated gestational diabetes, Obstet Gynecol sourceNot checked — no full text of the source

Separating plasma from cells by centrifugation within a few minutes of phlebotomy will attenuate glycolysis.

“Separating plasma from cells by centrifugation within a few minutes of phlebotomy will attenuate glycolysis.”

• AssumptionRests on an assumption: The diagnosis of gestational diabetes mellitus is totally dependent on accurate measurement of glucose.

There is evidence that women diagnosed with GDM early in pregnancy are more likely to have adverse outcomes.

“There is evidence that women diagnosed with GDM early in pregnancy are more likely to have adverse outcomes.”

• cites [281] Sweeting, 2016, Gestational diabetes mellitus in early pregnancy: evidence for poor pregnancy outcomes despite treatment, Diabetes Care sourceNot checked — no full text of the source

Sodium fluoride alone is not adequate to prevent glycolysis.

“Sodium fluoride alone is not adequate to prevent glycolysis.”

• AssumptionRests on an assumption: The diagnosis of gestational diabetes mellitus is totally dependent on accurate measurement of glucose.

Outcomes for women with GDM diagnosed before 12 weeks of gestation are similar to those in women with preexisting diabetes.

“For example, outcomes for women with GDM diagnosed before 12 weeks of gestation are similar to those in women with preexisting diabetes (281).”

• cites [281] Sweeting, 2016, Gestational diabetes mellitus in early pregnancy: evidence for poor pregnancy outcomes despite treatment, Diabetes Care sourceNot checked — no full text of the source

Semiquantitative urine glucose tests cannot distinguish between euglycemia and hypoglycemia.

“Semiquantitative urine glucose tests also cannot distinguish between euglycemia and hypoglycemia.”

Small changes in HbA1c (e.g., ±0.3%) over time may reflect assay variability rather than a true change in glycemic status.

“Small changes in HbA 1c (e.g., ± 0.3% HbA 1c ) over time may reflect assay variability rather than a true change in glycemic status (361).”

• cites [361] Little, 2011, Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care, Clin Chem sourceNot checked — no full text of the source

The concentration of AGEs in dermal collagen correlated more strongly with the presence of complications than the mean HbA1c values over time.

“Interestingly, the concentration of AGEs in dermal collagen correlated more strongly with the presence of complications than the mean HbA 1c values over time (378).”

• cites [378] Monnier, 1999, Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial, Diabetes sourceNot checked — no full text of the source

In the DCCT, adults and adolescents with type 1 diabetes randomized to maintain lower average blood glucose concentrations exhibited a significantly lower incidence of microvascular complications, namely diabetic retinopathy, nephropathy, and neuropathy.

“In the Diabetes Control and Complications Trial (DCCT), adults and adolescents with type 1 diabetes randomized to maintain lower average blood glucose concentrations exhibited a significantly lower incidence of microvascular complications, namely diabetic retinopathy, nephropathy, and neuropathy (50).”

• cites [50] Nathan, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med sourceNot checked — no full text of the source

There is a direct relationship between the degree of glycemia and the risk of renal, retinal, and neurological complications.

“There is a direct relationship between the degree of glycemia and the risk of renal, retinal, and neurological complications.”

• cites [48] The Diabetes Control and Complications Trial Research Group, 1995, The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial, Diabetes sourceNot checked — no full text of the source
• cites [49] Stratton, 2000, Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study, BMJ sourceNot checked — no full text of the source

The onset of type 2 diabetes has been estimated to occur approximately 4 to 7 (or more) years before clinical diagnosis.

“In the past, the onset of type 2 diabetes has been estimated to occur approximately 4 to 7 (or more) years before clinical diagnosis (26)”

• cites [26] Harris, 1993, Undiagnosed NIDDM: clinical and public health issues, Diabetes Care sourceNot checked — no full text of the source

There is no published evidence that treatment based on screening influences long-term complications.

“there is yet no published evidence that treatment based on screening influences long-term complications.”

2-h postload glucose >11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test is diagnostic of diabetes.

“(b) 2-h postload glucose >11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test (OGTT)”

• cites [18] The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 1997, Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Diabetes Care sourceNot checked — no full text of the source

The UKPDS in people with short-duration type 2 diabetes showed that intensive blood glucose control significantly reduced microvascular complications.

“The United Kingdom Prospective Diabetes Study (UKPDS) in people with short-duration type 2 diabetes showed that intensive blood glucose control significantly reduced microvascular complications (52).”

• cites [52] UK Prospective Diabetes Study (UKPDS) Group, 1998, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33), Lancet sourceNot checked — no full text of the source

If a within-person biological CV of 5.7% (from the NHANES study) is applied to a true glucose concentration of 7.0 mmol/L (126 mg/dL), the 95% CI would encompass glucose concentrations of 6.2 to 7.8 mmol/L (112 to 140 mg/dL).

“If a within-person biological CV of 5.7% (from the NHANES study) is applied to a true glucose concentration of 7.0 mmol/L (126 mg/dL), the 95% CI would encompass glucose concentrations of 6.2 to 7.8 mmol/L (112 to 140 mg/dL).”

Enzymatic methods for glucose analysis are relatively well standardized.

“Enzymatic methods for glucose analysis are relatively well standardized.”

If similar biases occur with plasma, individuals near the diagnostic threshold could be misclassified.

“If, as is likely, similar biases occur with plasma, individuals near the diagnostic threshold could be misclassified.”

In the DCCT, participants with type 1 achieved glycemic control by performing BGM at least four times per day to guide insulin therapy.

“In the DCCT, participants with type 1 achieved glycemic control by performing BGM at least four times per day to guide insulin therapy (50).”

• cites [50] Nathan, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med sourceNot checked — no full text of the source

The CAP data revealed that at a plasma glucose concentration of approximately 7.1 mmol/L (128 mg/dL), imprecision among laboratories using the same method had a coefficient of variation (CV) #2.7%.

“The CAP data revealed that at a plasma glucose concentration of approximately 7.1 mmol/L (128 mg/dL), imprecision among laboratories using the same method had a coefficient of variation (CV) #2.7% (85).”

• cites [85] Sacks, 2023, CarbohydratesNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

A study published in 2018, which measured fasting serum glucose in 89 healthy individuals for 10 consecutive weeks (mean of 9 samples per subject), observed within-and between-person CVs of 4.7% and 8.1%, respectively, at a glucose concentration of approximately 4.6 mmol/L (83 mg/dL).

“A study published in 2018, which measured fasting serum glucose in 89 healthy individuals for 10 consecutive weeks (mean of 9 samples per subject), observed within-and betweenperson CVs of 4.7% and 8.1%, respectively, at a glucose concentration of approximately 4.6 mmol/L (83 mg/dL) (95).”

• cites [95] Aarsand, 2018, The EuBIVAS: within- and between-subject biological variation data for electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, Clin Chem sourceNot checked — no full text of the source

Analysis of 685 adults from NHANES III found mean within-person variability of FPG measured 2 to 4 weeks apart was 5.7% (95% CI, 5.3% to 6.1%).

“Similar findings were obtained with analysis of 685 adults from NHANES III, where mean withinperson variability of FPG measured 2 to 4 weeks apart was 5.7% (95% CI, 5.3% to 6.1%) (93).”

• cites [93] Selvin, 2007, Short-term variability in measures of glycemia and implications for the classification of diabetes, Arch Intern Med sourceNot checked — no full text of the source

Compared with a reference measurement procedure, significant (P < 0.001) bias (up to 13%) was observed for 40.6% of the peer groups.

“However, compared with a reference measurement procedure, significant (P < 0.001) bias (up to 13%) was observed for 40.6% of the peer groups (86).”

• cites [86] Miller, 2008, State of the art in trueness and interlaboratory harmonization for 10 analytes in general clinical chemistry, Arch Pathol Lab Med sourceNot checked — no full text of the source

A meta-analysis published in 2019 identified 23 publications that delivered 46 different estimates of glucose biological variation.

“A meta-analysis published in 2019 (96) identified 23 publications that delivered 46 different estimates of glucose biological variation.”

• cites [96] González-Lao, 2019, Systematic review of the biological variation data for diabetes related analytes, Clin Chim Acta sourceNot checked — no full text of the source

The 95% CI for a fasting glucose concentration of 7.0 mmol/L (126 mg/dL) would be 7.0 mmol/L ± 6.4% (126 mg/dL ± 6.4%), namely, 6.1 to 7.9 mmol/L (110 to 142 mg/dL).

“Thus, the 95% CI for a fasting glucose concentration of 7.0 mmol/L (126 mg/dL) would be 7.0 mmol/L ± 6.4% (126 mg/dL ± 6.4%), namely, 6.1 to 7.9 mmol/L (110 to 142 mg/dL).”

Estimates of biological variation from 11 studies deemed suitable for inclusion in the meta-analysis (main reasons for exclusion were unhealthy or elderly individuals) yielded within-and between-person CVs of 4.8% and 7.9%, respectively.

“Estimates of biological variation from 11 studies deemed suitable for inclusion in the meta-analysis (main reasons for exclusion were unhealthy or elderly individuals) yielded within-and between-person CVs of 4.8% and 7.9%, respectively.”

• cites [96] González-Lao, 2019, Systematic review of the biological variation data for diabetes related analytes, Clin Chim Acta sourceNot checked — no full text of the source

Using assay imprecision of 3% (CV) only (excluding biological variability) would yield 95% CI of 6.6 to 7.4 mmol/L (118 to 134 mg/dL) among laboratories for a true glucose concentration of 7.0 mmol/L (126 mg/dL).

“Using assay imprecision of 3% (CV) only (excluding biological variability) would yield 95% CI of 6.6 to 7.4 mmol/L (118 to 134 mg/dL) among laboratories for a true glucose concentration of 7.0 mmol/L (126 mg/dL).”

Glucose concentrations in healthy individuals vary with age.

“Glucose concentrations in healthy individuals vary with age.”

• cites [66] Rifai, 2017, CarbohydratesNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Comparison of results from approximately 6,000 clinical laboratories reveals that the mean glucose concentrations measured in serum samples by the hexokinase and glucose oxidase methods are essentially the same.

“Comparison of results from approximately 6,000 clinical laboratories reveals that the mean glucose concentrations measured in serum samples by the hexokinase and glucose oxidase methods are essentially the same (86).”

• cites [86] Miller, 2008, State of the art in trueness and interlaboratory harmonization for 10 analytes in general clinical chemistry, Arch Pathol Lab Med sourceNot checked — no full text of the source

Analysis of proficiency surveys conducted in 2019 by the College of American Pathologists (CAP) reveals that hexokinase or glucose oxidase is used in virtually all the analyses performed in the U.S.

“Analysis of proficiency surveys conducted in 2019 by the College of American Pathologists (CAP) reveals that hexokinase or glucose oxidase is used in virtually all the analyses performed in the U.S. (85).”

• cites [85] Sacks, 2023, CarbohydratesNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Glucose concentrations in plasma are approximately 11% higher than in whole blood if the hematocrit is normal.

“Therefore, glucose concentrations in plasma are approximately 11% higher than in whole blood if the hematocrit is normal.”

Analysis of larger numbers of individuals from the same NHANES III database yielded within-and between-person CVs of 8.3% and 12.5%, respectively, at a glucose concentration of approximately 5.1 mmol/L (92 mg/dL).

“Analysis of larger numbers of individuals from the same NHANES III database yielded within-and between-person CVs of 8.3% and 12.5%, respectively, at a glucose concentration of approximately 5.1 mmol/L (92 mg/dL) (94).”

• cites [94] Lacher, 2005, Estimate of biological variation of laboratory analytes based on the third national health and nutrition examination survey, Clin Chem sourceNot checked — no full text of the source

Despite the low analytical imprecision at the diagnostic decision limits of 7.0 mmol/L (126 mg/dL) and 11.1 mmol/L (200 mg/dL), classification errors may occur.

“Despite the low analytical imprecision at the diagnostic decision limits of 7.0 mmol/L (126 mg/dL) and 11.1 mmol/L (200 mg/dL), classification errors may occur.”

The use of blood collection tubes containing citrate, sodium fluoride, and EDTA offers a practical solution to the problem of glycolysis.

“The use of blood collection tubes containing citrate, sodium fluoride, and EDTA offers a practical solution to the problem of glycolysis.”

Meters that are designed for home BGM often do not meet the needs of testing in hospitals, especially because of the danger of transmission of pathogens from one patient to another via the meters.

“Meters that are designed for home BGM often do not meet the needs of testing in hospitals, especially because of the danger of transmission of pathogens from one patient to another via the meters.”

Changing from one meter to a meter with less meter error (bias) was associated with decreased glycemic variability and increased percentage of values in target glucose range in patients following cardiovascular surgery.

“Changing from one meter to a meter with less meter error (bias) was associated with decreased glycemic variability and increased percentage of values in target glucose range in patients following cardiovascular surgery (131).”

• cites [131] Karon, 2015, Impact of glucose meter error on glycemic variability and time in target range during glycemic control after cardiovascular surgery, J Diabetes Sci Technol sourceNot checked — no full text of the source

The evidence is insufficient to recommend routine use of BGM for people with type 2 diabetes whose diabetes is treated without use of insulin.

“In summary, the evidence is insufficient to recommend routine use of BGM for people with type 2 diabetes whose diabetes is treated without use of insulin.”

There is insufficient evidence to conclude whether the observed small and transient differences in HbA 1c lowering associated with BGM improved clinically important outcomes.

“There is insufficient evidence to conclude whether the observed small and transient differences in HbA 1c lowering associated with BGM improved clinically important outcomes.”

That study revealed that meters that achieve both an imprecision (as CV) <5% and a bias <5% rarely lead to major errors in insulin dosing.

“That study revealed that meters that achieve both an imprecision (as CV) <5% and a bias <5% rarely lead to major errors in insulin dosing.”

• cites [126] Boyd, 2001, Quality specifications for glucose meters: assessment by simulation modeling of errors in insulin dose, Clin Chem sourceNot checked — no full text of the source

People using insulin, particularly those with type 1 diabetes, use knowledge of ambient capillary (with BGM) or interstitial (with CGM) glucose concentrations as an aid in determining basal insulin requirements and in selecting appropriate insulin doses for meals and at different times of the day.

“People using insulin, particularly those with type 1 diabetes, use knowledge of ambient capillary (with BGM) or interstitial (with CGM) glucose concentrations as an aid in determining basal insulin requirements and in selecting appropriate insulin doses for meals and at different times of the day (107).”

• cites [107] American Diabetes Association, 1996, Self-monitoring of blood glucose, Diabetes Care sourceNot checked — no full text of the source

A simulation modeling study quantified the effect of meter errors on the rate of insulin doses differing from the dose intended for the actual glucose concentration.

“A simulation modeling study quantified the effect of meter errors on the rate of insulin doses differing from the dose intended for the actual glucose concentration (126).”

• cites [126] Boyd, 2001, Quality specifications for glucose meters: assessment by simulation modeling of errors in insulin dose, Clin Chem sourceNot checked — no full text of the source

Professional-use meters that are selected on the basis of their performance in a population outside the newborn nursery and newborn intensive care unit (ICU) are not necessarily the optimal choice for use in newborns.

“Professional-use meters that are selected on the basis of their performance in a population outside the newborn nursery and newborn intensive care unit (ICU) are not necessarily the optimal choice for use in newborns (132).”

• cites [132] Warner, 2011, Can one point-of-care glucose meter be used for all pediatric and adult hospital patients? Evaluation of three meters, including recently modified test strips, Diabetes Technol Ther sourceNot checked — no full text of the source

In a study of individuals aged 1 to over 65 years and treated with insulin, HbA 1c showed greater improvement with BGM performed 4 or more times per day than with BGM performed less frequently.

“In a study of individuals aged 1 to over 65 years and treated with insulin, HbA 1c showed greater improvement with BGM performed 4 or more times per day than with BGM performed less frequently (152).”

• cites [152] Schütt, 2006, Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria, Exp Clin Endocrinol Diabetes sourceNot checked — no full text of the source

Maltose interferes with measurements by some glucose meters that use glucose dehydrogenase.

“Maltose interferes with measurements by some glucose meters that use glucose dehydrogenase (139).”

• cites [139] Perera, 2011, The danger of using inappropriate point-of-care glucose meters in patients on icodextrin dialysis, Diabet Med sourceNot checked — no full text of the source

Concerns about accuracy resulted in early generations of CGM being approved only for adjunctive use.

“Concerns about accuracy resulted in early generations of CGM being approved only for adjunctive use (e.g., capillary glucose was to be measured by a blood glucose meter to make treatment decisions, such as deciding how much insulin to take).”

HAPO was a large (approximately 25,000 pregnant women) prospective multinational epidemiologic study to assess adverse outcomes as a function of maternal glycemia.

“HAPO was a large (approximately 25,000 pregnant women) prospective multinational epidemiologic study to assess adverse outcomes as a function of maternal glycemia.”

• cites [248] Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med sourceNot checked — no full text of the source

The same source of variability, if present in human tears, may be at least partly responsible for the inability to establish a clinically sound blood-to-tear correlation in human subjects.

“The same source of variability, if present in human tears, may be at least partly responsible for the inability to establish a clinically sound blood-to-tear correlation in human subjects (247).”

• cites [247] Yan, 2011, Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration, Anal Chem sourceNot checked — no full text of the source

During the COVID-19 pandemic, the FDA allowed use of CGM devices with remote monitoring in hospitals in the U.S. to potentially reduce transmission of the virus.

“However, during the coronavirus disease 2019 (COVID-19) pandemic, the FDA allowed use of CGM devices with remote monitoring in hospitals in the U.S. to potentially reduce transmission of the virus (194).”

• cites [194] U.S. Food and Drug Administration . Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency (Revised), 2020. Accessed 2 September 2020. Available from https://www.fda.gov/media/136290/downloadNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.