2. Diagnosis and classification of diabetes: standards of care in diabetes-2025

May combine two claims.

The rate of b-cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults).

“The rate of b-cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults) (44,58).”

• cites [44] Bogun, 2020, C-peptide levels in subjects followed longitudinally before and after type 1 diabetes diagnosis in TrialNet, Diabetes Care sourcePartly supported

  The Introduction (page unavailable) reports that adults have a slower rate of C-peptide decline than children, and the Results find that age influences that rate. This supports the age-related pattern, but the paper measures C-peptide as an indicator of β-cell function, not the rate of β-cell destruction, and its participants were aged 3.9 years or older, so it does not establish the claim about infants. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [58] Greenbaum, 2012, Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes TrialNet data, Diabetes sourcePartly supported

  The Results report variation in individual C-peptide decline, and the Discussion says decline was faster at ages 7–21 than above age 21. But the paper measures β-cell function after diagnosis, not destruction directly, and explicitly says its data cannot support conclusions about children younger than 7, including infants (Discussion; page unavailable). (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Adults may retain sufficient b-cell function to prevent DKA for many years; such individuals may have remission characterized by decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA.

“Adults may retain sufficient b-cell function to prevent DKA for many years; such individuals may have remission characterized by decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA (33-35, 59,60).”

• cites [33] Humphreys, 2019, Individual and diabetes presentation characteristics associated with partial remission status in children and adults evaluated up to 12months following diagnosis of type 1 diabetes: an ADDRESS-2 (After Diagnosis Diabetes Research Support System-2) study analysis, Diabetes Res Clin Pract sourceNot checked — no full text of the source
• cites [34] Thomas, 2019, Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes, Diabetologia 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
• cites [35] Hope, 2016, Practical Classification Guidelines for Diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis, Br J Gen Pract 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
• cites [59] Mishra, 2018, A global perspective of latent autoimmune diabetes in adults, Trends Endocrinol Metab sourceNot checked — no full text of the source
• cites [60] Buzzetti, 2017, Adult-onset autoimmune diabetes: current knowledge and implications for management, Nat Rev Endocrinol sourceNot checked — no full text of the source

May combine two claims.

A1C may not be a suitable diagnostic test in people with anemia, people treated with erythropoietin, or people undergoing hemodialysis or HIV treatment.

“A1C may not be a suitable diagnostic test in people with anemia, people treated with erythropoietin, or people undergoing hemodialysis or HIV treatment (1,19,20).”

• cites [1] Sacks, 2023, Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus, Diabetes Care sourcePartly supported

  The 'Other Patient-Related Factors and Interfering Factors' section (page unavailable) says altered red-blood-cell turnover can make HbA1c results spurious and require glucose testing for diagnosis; it specifically discusses hemolytic and iron-deficiency anemia. The passages found do not address erythropoietin treatment, hemodialysis, or HIV treatment as reasons A1C may be unsuitable for diagnosis. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [19] Eckhardt, 2012, Glycated hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals, AIDS Patient Care STDS sourcePartly supported

  The Introduction (page not provided) notes that HbA1c screening may be unsuitable with abnormal red-cell turnover, including iron-deficiency anemia. The Discussion (page not provided) finds HbA1c insensitive for diagnosing diabetes in HIV-infected patients, though it also calls HbA1c a practical screening option when used with fasting blood glucose. Our copy does not address erythropoietin treatment or hemodialysis, and it does not establish the same concern for every form of anemia. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [20] Kim, 2009, A1C underestimates glycemia in HIV infection, Diabetes Care sourceSupported

May combine two claims.

At stage 1 of type 1 diabetes, the 5-year risk of developing symptomatic type 1 diabetes is 44% overall but varies considerably based on number, titer, and specificity of autoantibodies as well as age of seroconversion and genetic risk.

“At stage 1, the 5-year risk of developing symptomatic type 1 diabetes is 44% overall but varies considerably based on number, titer, and specificity of autoantibodies as well as age of seroconversion and genetic risk (45).”

• cites [45] Insel, 2015, Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association, Diabetes Care sourcePartly supported

  The Overview of Staging, Stage 1 section gives an approximately 44% five-year risk for children screened for genetic risk at birth who reach stage 1, not an overall estimate for everyone at stage 1. The Stage 1 section supports variation by autoantibody number, titer and type, age at seroconversion, and HLA genotype. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

At stage 2 of type 1 diabetes, there is 60% risk by 2 years and 75% risk within 5 years of developing a clinical diagnosis of type 1 diabetes.

“At stage 2 of the disease, there is 60% risk by 2 years and 75% risk within 5 years of developing a clinical diagnosis of type 1 diabetes (55,56).”

• cites [55] Sosenko, 2009, Incident dysglycemia and progression to type 1 diabetes among participants in the Diabetes Prevention Trial-Type 1, Diabetes Care sourcePartly supported

  The Results report that dysglycemia predicted progression to clinical type 1 diabetes, and that 75% of a small subgroup of children under 13 with persistent dysglycemia developed it during a maximum follow-up of 4.5 years. They do not report a 60% risk by two years or a 75% five-year risk for everyone at stage 2; the reported five-year estimate for children under 13 with dysglycemia was 94%. Page numbers were not available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [56] Krischer, 2013, The use of intermediate endpoints in the design of type 1 diabetes prevention trials, Diabetologia sourcePartly supported

  The Results report a 74% risk of type 1 diabetes four years after confirmed dysglycaemia, close to the claimed 75% but at a different time point. They do not report a 60% risk of clinical diagnosis at two years; the two-year figure for this group is a 41% risk of progressing from normal glucose tolerance to dysglycaemia. No page number is available in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

The features most useful in determination of type 1 diabetes include younger age at diagnosis (<35 years) with lower BMI (<25 kg/m2), unintentional weight loss, ketoacidosis, and plasma glucose >360 mg/dL (>20 mmol/L) at presentation.

“The features most useful in determination of type 1 diabetes include younger age at diagnosis (<35 years) with lower BMI (<25 kg/m 2 ), unintentional weight loss, ketoacidosis, and plasma glucose >360 mg/dL (>20 mmol/L) at presentation (36) (Fig.”

• cites [36] Holt, 2021, The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), Diabetes Care sourceSupported

May combine two claims.

Misdiagnosis is common and can occur in 40% of adults with new type 1 diabetes (e.g., adults with type 1 diabetes misdiagnosed as having type 2 diabetes).

“and that misdiagnosis is common and can occur in 40% of adults with new type 1 diabetes (e.g., adults with type 1 diabetes misdiagnosed as having type 2 diabetes).”

• cites [36] Holt, 2021, The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), Diabetes Care sourcePartly supported

  The “Differentiating Type 1 Diabetes From Type 2 Diabetes” section says misclassification is common and that over 40% of people developing type 1 diabetes after age 30 are initially treated as having type 2 diabetes. The claim omits the age-after-30 qualifier, presenting the figure as applying to adults with new type 1 diabetes generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

FPG, 2-h PG, and A1C reflect different aspects of glucose metabolism, and diagnostic cut points for the different tests will identify groups with incomplete concordance.

“FPG, 2-h PG, and A1C reflect different aspects of glucose metabolism, and diagnostic cut points for the different tests will identify groups with incomplete concordance (3).”

• cites [3] International Expert Committee, 2009, International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes, Diabetes Care sourceSupported

May combine two claims.

Occasionally, people with type 2 diabetes may present with DKA, particularly members of certain racial, ethnic, and ancestral groups (e.g., African American and Hispanic/Latino adults), who may present with ketosis-prone type 2 diabetes.

“Occasionally, people with type 2 diabetes may present with DKA (37), particularly members of certain racial, ethnic, and ancestral groups (e.g., African American and Hispanic/Latino adults), who may present with ketosisprone type 2 diabetes (30).”

• cites [37] Zhong, 2018, Trends in hospital admission for diabetic ketoacidosis in adults with type 1 and type 2 diabetes in England, 1998-2013: a retrospective cohort study, Diabetes Care sourceNot checked — no full text of the source
• cites [30] Umpierrez, 2024, Hyperglycemic crises in adults with diabetes: a consensus report, Diabetes Care sourceSupported

May combine two claims.

Diagnostic accuracy may be improved by using higher-specificity tests, using confirmatory testing for other autoantibodies, and restricting testing to those with clinical features suggestive of autoimmune diabetes.

“Diagnostic accuracy may be improved by using higher-specificity tests, using confirmatory testing for other autoantibodies, and restricting testing to those with clinical features suggestive of autoimmune diabetes (48).”

• cites [48] Jones, 2021, Latent autoimmune diabetes of adults (LADA) is likely to represent a mixed population of autoimmune (type 1) and nonautoimmune (type 2) diabetes, Diabetes Care sourceSupported

May combine two claims.

Of 585 children who developed more than two autoantibodies, nearly 70% developed type 1 diabetes within 10 years and 84% within 15 years.

“Of the 585 children who developed more than two autoantibodies, nearly 70% developed type 1 diabetes within 10 years and 84% within 15 years (40).”

• cites [40] Ziegler, 2013, Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children, JAMA sourcePartly supported

  The Results section (“Children With Multiple Islet Autoantibodies”; page not provided) reports 585 children and estimated diabetes progression of 69.7% at 10 years and 84.2% at 15 years after seroconversion. But “multiple” includes children with two autoantibodies, whereas the claim says more than two. The reported percentages are follow-up risk estimates, not counts of children who developed diabetes. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

This immune-related adverse event occurs in just under 1% of checkpoint inhibitor-treated individuals but most commonly occurs with agents that block the programmed cell death protein 1/programmed cell death ligand 1 pathway alone or in combination with other checkpoint inhibitors.

“This immune-related adverse event occurs in just under 1% of checkpoint inhibitortreated individuals but most commonly occurs with agents that block the programmed cell death protein 1/programmed cell death ligand 1 pathway alone or in combination with other checkpoint inhibitors (66).”

• cites [66] Stamatouli, 2018, Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors, Diabetes sourceSupported

May combine two claims.

Testing coupled with education about diabetes symptoms and close follow-up has been shown to enable earlier diagnosis and to prevent DKA.

“Such testing, coupled with education about diabetes symptoms and close follow-up, has been shown to enable earlier diagnosis and to prevent DKA (77,78).”

• cites [77] Barker, 2004, Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up, Diabetes Care sourceSupported
• cites [78] Elding Larsson, 2014, Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease, Pediatr Diabetes sourcePartly supported

  The Discussion says that monitoring with screening and repeated education about symptoms may improve outcomes, and that TEDDY children had low DKA rates compared with the general population. It also links close follow-up to early diagnosis. But the Results report DKA in 8 of 100 children, so the paper supports a lower DKA rate, not a categorical claim that follow-up prevents DKA. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Many genetic risk studies have been performed in populations of European ancestry and discriminatory ability may differ in those of different ancestry.

“As many genetic risk studies have been performed in populations of European ancestry and discriminatory ability may differ in those of different ancestry, more large case-control cohorts from non-European populations are still needed (82).”

• cites [82] Luckett, 2023, Utility of genetic risk scores in type 1 diabetes, Diabetologia sourceSupported

Classified as probably not a substantial claim.

ADA clinical guidance concluded that A1C, FPG, or 2-h PG also could be used to test for prediabetes or type 2 diabetes in children and adolescents.

“However, ADA clinical guidance concluded that A1C, FPG, or 2-h PG also could be used to test for prediabetes or type 2 diabetes in children and adolescents (114).”

• cites [114] Arslanian, 2018, Evaluation and management of youth-onset type 2 diabetes: a position statement by the American Diabetes Association, Diabetes Care sourceSupported

May combine two claims.

The ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in people of reproductive age, with an increase in the number of pregnant individuals with undiagnosed type 2 diabetes in early pregnancy.

“The ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in people of reproductive age, with an increase in the number of pregnant individuals with undiagnosed type 2 diabetes in early pregnancy (164-166).”

• cites [164] Feig, 2014, Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996-2010, Diabetes Care sourceNot checked — no full text of the source
• cites [165] Peng, 2017, Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996-2014, Am J Obstet Gynecol sourcePartly supported

  The Comments report increasing pregestational type 2 diabetes and suggest that rising obesity among women of reproductive age likely contributed. But Materials and Methods says the study identified diabetes clinically recognized before pregnancy; it does not establish an increase in undiagnosed type 2 diabetes in early pregnancy. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [166] Jovanovič, 2015, Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy, Diabetes Metab Res Rev sourcePartly supported

  The Introduction and Results report increasing type 2 diabetes among women of child-bearing age and pregnant women. The Introduction gives an estimate of undiagnosed diabetes only for US adults generally; it does not establish an increase among pregnant people in early pregnancy. The paper also does not attribute the increase to obesity. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Use of immunosuppressive therapies is a major contributor to the development of PTDM, but the risks of transplant rejection outweigh the risks of PTDM.

“Although the use of immunosuppressive therapies is a major contributor to the development of PTDM, the risks of transplant rejection outweigh the risks of PTDM, and the role of the diabetes health care professional is to treat hyperglycemia appropriately regardless of the type of immunosuppression (138).”

• cites [138] Sharif, 2014, Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions, Am J Transplant sourcePartly supported

  Recommendation 5 (page not provided) identifies immunosuppression as the major modifiable risk factor for PTDM and advises choosing regimens for patient and graft survival rather than PTDM risk alone. It calls for balancing PTDM against rejection risk, however, rather than saying rejection risk always outweighs PTDM risk. Recommendation 6 recommends treating posttransplant hyperglycemia, but does not specifically assign that role to diabetes health care professionals regardless of immunosuppression type. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in people with cystic fibrosis, occurring in about 20% of adolescents and 40-50% of adults.

“Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in people with cystic fibrosis, occurring in about 20% of adolescents and 40-50% of adults (127).”

• cites [127] Ode, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: management of cystic fibrosis-related diabetes in children and adolescents, Pediatr Diabetes sourceSupported

Classified as probably not a substantial claim. May combine two claims.

A1C is not recommended for screening for CFRD due to low sensitivity; however, a value of >=6.5% is consistent with a diagnosis of CFRD and reduces patient screening burden.

“A1C is not recommended for screening due to low sensitivity; however, a value of $6.5% ($48 mmol/mol) is consistent with a diagnosis of CFRD and reduces patient screening burden (129-131).”

• cites [129] Gilmour, 2019, Response to the letter to the editor from Dr. Boudreau et al, “Validation of a stepwise approach using glycated hemoglobin levels to reduce the number of required oral glucose tolerance tests to screen for cystic fibrosis-related diabetes in adults, Can J Diabetes sourceNot checked — no full text of the source
• cites [130] Gilmour, 2019, Cystic fibrosis-related diabetes screening in adults: a gap analysis and evaluation of accuracy of glycated hemoglobin levels, Can J Diabetes sourceNot checked — no full text of the source
• cites [131] Darukhanavala, 2021, Use of hemoglobin A1c to identify dysglycemia in cystic fibrosis, PLoS One sourcePartly supported

  The Discussion says HbA1c has low sensitivity for diagnosing CFRD and that guidelines do not recommend it for screening. Our copy does not state that an HbA1c value of ≥6.5% diagnoses CFRD; its Introduction presents reduced screening burden only as a potential benefit if HbA1c proved suitable, while its Conclusion does not support its use for screening pre-CFRD dysglycemia. Page numbers are not available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

MODY is inherited in an autosomal dominant pattern with abnormalities in at least 14 genes on different chromosomes identified to date.

“It is inherited in an autosomal dominant pattern with abnormalities in at least 14 genes on different chromosomes identified to date (152).”

• cites [152] Greeley, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of monogenic diabetes in children and adolescents, Pediatr Diabetes sourcePartly supported

  The section on autosomal dominant familial mild hyperglycemia or diabetes (MODY; page unavailable) says known MODY subtypes involve dominantly acting mutations and that at least 14 genes have been reported to cause a MODY-like phenotype. It does not establish that those genes are all on different chromosomes, and it qualifies the count as genes reported to cause a MODY-like phenotype. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The Cystic Fibrosis Foundation Patient Registry evaluated 3,553 people with cystic fibrosis and identified 445 (13%) with CFRD.

“The Cystic Fibrosis Foundation Patient Registry (132) evaluated 3,553 people with cystic fibrosis and identified 445 (13%) with CFRD.”

• cites [132] Franck Thompson, 2020, The association of pediatric cystic fibrosis-related diabetes screening on clinical outcomes by center: a CF patient registry study, J Cyst Fibros sourceSupported

May combine two claims.

Posttransplantation hyperglycemia is an important risk factor for subsequent PTDM; a formal diagnosis of PTDM is optimally made once the individual is stable on maintenance immunosuppression (usually at least 45 days) and in the absence of acute infection.

“Whereas posttransplantation hyperglycemia is an important risk factor for subsequent PTDM, a formal diagnosis of PTDM is optimally made once the individual is stable on maintenance immunosuppression (usually at least 45 days) and in the absence of acute infection (138,(142)(143)(144)147).”

• cites [138] Sharif, 2014, Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions, Am J Transplant 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
• cites [142] Thomas, 2000, Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes, BMC Nephrol 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 [143] Chakkera, 2009, Hyperglycemia during the immediate period after kidney transplantation, Clin J Am Soc Nephrol 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

May combine two claims.

The A1C test may underestimate glycemia in people with HIV, so plasma glucose criteria are preferred to diagnose prediabetes and diabetes.

“As the A1C test may underestimate glycemia in people with HIV, plasma glucose criteria are preferred to diagnose prediabetes and diabetes (20).”

• cites [20] Kim, 2009, A1C underestimates glycemia in HIV infection, Diabetes Care sourcePartly supported

  The Abstract Results and Conclusions report that A1C underestimated glycemia in the HIV-infected patients studied. The paper does not recommend plasma glucose criteria over A1C for diagnosing prediabetes or diabetes; its Conclusions instead suggest that fructosamine may be more appropriate for assessing glycemia in this setting. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Correct diagnosis of monogenic forms of diabetes is critical because people who have them may be incorrectly diagnosed with type 1 or type 2 diabetes, leading to suboptimal, even potentially harmful, treatment plans and delays in diagnosing other family members.

“Correct diagnosis of monogenic forms of diabetes is critical because people who have them may be incorrectly diagnosed with type 1 or type 2 diabetes, leading to suboptimal, even potentially harmful, treatment plans and delays in diagnosing other family members (152).”

• cites [152] Greeley, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of monogenic diabetes in children and adolescents, Pediatr Diabetes sourceSupported

May combine two claims.

Preconception care of people with known preexisting diabetes results in lower A1C and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age birth weight, and neonatal intensive care unit admission.

“The preconception care of people with known preexisting diabetes results in lower A1C and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age birth weight, and neonatal intensive care unit admission (173).”

• cites [173] Wahabi, 2020, Systematic review and meta-analysis of the effectiveness of pre-pregnancy care for women with diabetes for improving maternal and perinatal outcomes, PLoS One sourcePartly supported

  The Conclusion (page not provided) reports lower HbA1c and reduced congenital malformations, perinatal mortality, and small-for-gestational-age births in women with pregestational diabetes. It says preconception care *may* reduce preterm delivery and NICU admission; the claim presents those two effects as unqualified results. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Community screening may be poorly targeted; it may fail to reach the groups most at risk and inappropriately test those at very low risk or even those who have already been diagnosed.

“Community screening may also be poorly targeted; i.e., it may fail to reach the groups most at risk and inappropriately test those at very low risk or even those who have already been diagnosed (110).”

• cites [110] Tabaei, 2003, Community-based screening for diabetes in Michigan, Diabetes Care sourceSupported

May combine two claims.

Genetic screening (i.e., next-generation sequencing) is increasingly available and cost-effective.

“Genetic screening (i.e., next-generation sequencing) is increasingly available and cost-effective (152).”

• cites [152] Greeley, 2022, ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of monogenic diabetes in children and adolescents, Pediatr Diabetes sourcePartly supported

  In ‘Selecting candidates for molecular testing,’ the guidelines say genetic testing is available in many countries and that NGS has a lower cost per gene. They also say NGS panels remain expensive and that cost-effectiveness depends on the condition and selection of patients; the claim presents cost-effectiveness without those qualifications. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Early abnormal glucose metabolism, defined as a fasting glucose threshold of 110 mg/dL or an A1C of 5.9%, may identify individuals who are at higher risk of adverse pregnancy and neonatal outcomes (preeclampsia, macrosomia, shoulder dystocia, and perinatal death), are at high risk of a later GDM diagnosis, and are more likely to need insulin treatment.

“Early abnormal glucose metabolism, defined as a fasting glucose threshold of 110 mg/dL (6.1 mmol/L) or an A1C of 5.9% (41 mmol/mol), may identify individuals who are at higher risk of adverse pregnancy and neonatal outcomes (preeclampsia, macrosomia, shoulder dystocia, and perinatal death), are at high risk of a later GDM diagnosis, and are more likely to need insulin treatment (174-176).”

• cites [174] 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

  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
• cites [175] Mañé, 2019, Association of first-trimester HbA1c levels with adverse pregnancy outcomes in different ethnic groups, Diabetes Res Clin Pract 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
• cites [176] Kattini, 2020, Early gestational diabetes mellitus screening with glycated hemoglobin: a systematic review, J Obstet Gynaecol Can sourceNot checked — no full text of the source

May combine two claims.

The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L]).

“The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial (195), the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L]).”

• cites [195] Crowther, 2005, Effect of treatment of gestational diabetes mellitus on pregnancy outcomes, N Engl J Med sourceSupported

May combine two claims.

A systematic review of economic evaluations of GDM screening found that the one-step method identified more cases of GDM and was more likely to be cost-effective than the two-step method.

“A systematic review of economic evaluations of GDM screening found that the one-step method identified more cases of GDM and was more likely to be cost-effective than the two-step method (211).”

• cites [211] Mo, 2021, Economic evaluations of gestational diabetes mellitus screening: a systematic review, J Epidemiol sourceSupported

May combine two claims.

The GDM diagnostic criteria for the 75-g OGTT from the IADPSG and the GDM screening and diagnostic criteria with the two-step approach were not derived from data in the first half of pregnancy.

“The GDM diagnostic criteria for the 75-g OGTT from the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) and the GDM screening and diagnostic criteria with the two-step approach were not derived from data in the first half of pregnancy”

• cites [179] McIntyre, 2016, Issues with the diagnosis and classification of hyperglycemia in early pregnancy, Diabetes Care sourcePartly supported

  In the main text (pp. 53–54), the paper contrasts standard GDM testing at 24–32 weeks with early pregnancy and says evidence is insufficient to recommend early-pregnancy OGTT cutoffs. This supports the point about applying IADPSG criteria in the first half of pregnancy, but the paper does not discuss the derivation of screening or diagnostic criteria for the two-step approach. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Post hoc GDM in individuals diagnosed with the one-step method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucose levels during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10-14 years of age compared with offspring of mothers without GDM.

“Post hoc GDM in individuals diagnosed with this method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucose levels during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10-14 years of age compared with offspring of mothers without GDM.”

• cites [198] Lowe, 2019, Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism, Diabetes Care sourceSupported
• cites [199] Scholtens, 2019, Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal glycemia and childhood glucose metabolism, Diabetes Care 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

May combine two claims.

The one-step strategy was anticipated to significantly increase the incidence of GDM (from 5-6% to 15-20%), primarily because only one abnormal value, not two, became sufficient to make the diagnosis.

“This one-step strategy was anticipated to significantly increase the incidence of GDM (from 5-6% to 15-20%), primarily because only one abnormal value, not two, became sufficient to make the diagnosis (191).”

• cites [191] Sacks, 2012, Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel-recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, Diabetes Care sourcePartly supported

  The HAPO Study summary (p. 1) says the IADPSG criteria require one or more glucose values at or above threshold and reports a GDM frequency of 17.8%, within the claimed 15–20% range. It does not give a previous rate of 5–6%, describe the increase as anticipated, or establish that the change from two abnormal values to one was its primary cause. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

GDM is often indicative of underlying beta-cell dysfunction, which confers marked increased risk for later development of glucose intolerance and diabetes in the mother after delivery.

“GDM is often indicative of underlying b-cell dysfunction (182), which confers marked increased risk for later development of glucose intolerance and diabetes in the mother after delivery (183-185).”

• cites [182] Buchanan, 2007, What is gestational diabetes?, Diabetes Care sourceNot checked — no full text of the source
• cites [183] Noctor, 2016, Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria, Eur J Endocrinol sourceNot checked — no full text of the source
• cites [184] Kim, 2002, Gestational diabetes and the incidence of type 2 diabetes: a systematic review, Diabetes Care sourceSupported
• cites [185] Liu, 2023, Risk factors associated with early postpartum glucose intolerance in women with a history of gestational diabetes mellitus: a systematic review and meta-analysis, Endocrine sourceNot checked — no full text of the source

May combine two claims.

Treatment of higher-threshold maternal hyperglycemia, as identified by the two-step approach, reduces rates of neonatal macrosomia, large-for-gestational-age births, and shoulder dystocia without increasing small-for-gestational-age births.

“Treatment of higherthreshold maternal hyperglycemia, as identified by the two-step approach, reduces rates of neonatal macrosomia, large-forgestational-age births (207), and shoulder dystocia without increasing small-forgestational-age births.”

• cites [207] Farrar, 2017, Treatments for gestational diabetes: a systematic review and meta-analysis, BMJ Open sourcePartly supported

  The Results (Packages of care and dietary modification trials; page unavailable) report reduced macrosomia, large-for-gestational-age births, and shoulder dystocia with treatment compared with routine care. The Discussion says the largest trials used criteria associated with more severe hyperglycaemia, but the review does not limit its pooled finding to women identified by a two-step approach. Its reported outcomes do not establish that treatment leaves small-for-gestational-age births unchanged. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

A1C is an indirect measure of glucose exposure, and factors that affect hemoglobin concentrations or erythrocyte turnover can affect A1C.

“A1C is an indirect measure of glucose exposure, and factors that affect hemoglobin concentrations or erythrocyte turnover can affect A1C (e.g., thalassemia or folate deficiency) (Table 2.3).”

May combine two claims.

Children and adolescents often present with DKA as the first manifestation of the disease, and rates in the U.S. have increased over the past 20 years.

“Children and adolescents often present with DKA as the first manifestation of the disease, and rates in the U.S. have increased over the past 20 years (30)(31)(32).”

• cites (30)(31)(32)Not matched

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

May combine two claims.

In at-risk cohorts followed from birth or a very young age, seroconversion rarely occurs before 6 months of age and there is a peak in seroconversion between 9 and 24 months of age.

“In at-risk cohorts followed from birth or a very young age, seroconversion rarely occurs before 6 months of age and there is a peak in seroconversion between 9 and 24 months of age (41)(42)(43).”

• cites (41)(42)(43)Not matched

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

May combine two claims.

Children with type 1 diabetes often present with the hallmark symptoms of polyuria/polydipsia, and approximately half present with DKA.

“Children with type 1 diabetes often present with the hallmark symptoms of polyuria/polydipsia, and approximately half present with DKA (30)(31)(32).”

• cites (30)(31)(32)Not matched

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

May combine two claims.

The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may progress to insulin replacement more slowly.

“The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may progress to insulin replacement more slowly (33)(34)(35).”

• cites (33)(34)(35)Not matched

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

Classified as probably not a substantial claim. May combine two claims.

Prediabetes and type 2 diabetes meet criteria for conditions in which early detection via screening is appropriate.

“Prediabetes and type 2 diabetes meet criteria for conditions in which early detection via screening is appropriate.”

• AssumptionRests on an assumption: Prediabetes is a significant risk factor for progression to diabetes as well as cardiovascular disease and several other cardiometabolic outcomes.
• AssumptionRests on an assumption: Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension.
• AssumptionRests on an assumption: Type 2 diabetes occurs more frequently in individuals with prediabetes, prior gestational diabetes mellitus, or polycystic ovary syndrome.
• AssumptionRests on an assumption: Type 2 diabetes is often associated with a strong genetic predisposition or family history in first-degree relatives (more so than type 1 diabetes).
• AssumptionRests on an assumption: Both prediabetes and type 2 diabetes are common and impose significant clinical and public health burdens.

May combine two claims.

Fulminant onset of type 1 diabetes can occur, with DKA and low or undetectable levels of C-peptide as a marker of endogenous b-cell function.

“Fulminant onset of type 1 diabetes can occur, with DKA and low or undetectable levels of C-peptide as a marker of endogenous b-cell function (63)(64)(65).”

• cites (63)(64)(65)Not matched

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

May combine two claims.

The findings in all three groups were the same, suggesting that the same sequence of events led to clinical disease in both sporadic and familial cases of type 1 diabetes.

“Remarkably, the findings in all three groups were the same, suggesting that the same sequence of events led to clinical disease in both “sporadic” and familial cases of type 1”

May combine two claims.

People with type 1 diabetes often present with acute symptoms of diabetes and markedly elevated blood glucose levels, and 25-50% are diagnosed with life-threatening DKA.

“People with type 1 diabetes often present with acute symptoms of diabetes and markedly elevated blood glucose levels, and 25-50% are diagnosed with life-threatening DKA (30)(31)(32).”

• cites (30)(31)(32)Not matched

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

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The incidence and prevalence of type 1 diabetes are increasing.

“The incidence and prevalence of type 1 diabetes are increasing (70).”

• cites [70] Gregory, 2022, Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study, Lancet Diabetes Endocrinol sourceNot checked — no full text of the source

May combine two claims.

The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity.

“The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity (95,96).”

• cites [95] U.S. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Estimates of Diabetes and Its Burden in the United States. Accessed 11 September 2024. Available from https://www.cdc.gov/diabetes/php/data-research/index.htmlNot matched

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

• cites [96] International Diabetes Federation . IDF Diabetes Atlas, 10th edition. Brussels, Belgium, International Diabetes Federation,2021. Accessed 5 August 2024. Available from https://www.diabetesatlas.org/atlas/tenth-edition/Not matched

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

May combine two claims.

During the COVID-19 pandemic, numbers of cases of hyperglycemia, DKA, and new diabetes increased, suggesting that SARS-CoV-2 is a trigger for or can unmask type 1 diabetes.

“During the coronavirus disease 2019 (COVID-19) pandemic, numbers of cases of hyperglycemia, DKA, and new diabetes increased, suggesting that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a trigger for or can unmask type 1 diabetes (68).”

• cites [68] Wang, 2023, COVID-19 as a trigger for type 1 diabetes, J Clin Endocrinol Metab sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

A diagnosis of one of the three most common forms of MODY, HNF1A-MODY, GCK-MODY, and HNF4A-MODY, allows for more cost-effective personalized therapy (i.e., no therapy for GCK-MODY and sulfonylureas as first-line therapy for HNF1A-MODY and HNF4A-MODY).

“A diagnosis of one of the three most common forms of MODY, HNF1A-MODY, GCK-MODY, and HNF4A-MODY, allows for more cost-effective personalized therapy (i.e., no therapy for GCK-MODY and sulfonylureas as first-line therapy for HNF1A-MODY and HNF4A-MODY).”

May combine two claims.

The rationale for the 3-year interval is that with this interval, the number of false-positive tests that require confirmatory testing will be reduced, and individuals with false-negative tests will be retested before substantial time elapses and complications develop.

“The rationale for the 3-year interval is that with this interval, the number of false-positive tests that require confirmatory testing will be reduced, and individuals with false-negative tests will be retested before substantial time elapses and complications develop (109).”

• cites [109] Johnson, 2005, The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age, Diabetes Care sourceNot checked — no full text of the source

May combine two claims.

Annual OGTTs are perceived as burdensome, and engagement in current CFRD screening guidelines is poor, with only 30% of adults with cystic fibrosis having annual OGTTs.

“Not unexpectedly, annual OGTTs are perceived as burdensome, and engagement in current CFRD screening guidelines is poor, with only 30% of adults with cystic fibrosis having annual OGTTs (128).”

• cites [128] Cystic Fibrosis Foundation . Patient Registry 2022 Annual Data Report. Bethesda, MD, Cystic Fibrosis Foundation, 2022. Accessed 5 August 2024. Available from https://www.cff.org/media/31216/downloadNot matched

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

May combine two claims.

New-onset diabetes is estimated to occur in more than 5% of individuals infected with HIV on PIs, whereas more than 15% may have prediabetes.

“New-onset diabetes is estimated to occur in more than 5% of individuals infected with HIV on PIs, whereas more than 15% may have prediabetes (107).”

• cites [107] Monroe, 2015, Diagnosing and managing diabetes in HIV-infected patients: current concepts, Clin Infect Dis sourceNot checked — no full text of the source

May combine two claims.

Many cases of GDM represent preexisting hyperglycemia that is detected by routine screening in pregnancy, as routine screening is not widely performed in nonpregnant individuals of reproductive age.

“First, the best evidence reveals that many cases of GDM represent preexisting hyperglycemia that is detected by routine screening in pregnancy, as routine screening is not widely performed in nonpregnant individuals of reproductive age.”

• AssumptionRests on an assumption: Routine screening for diabetes is not widely performed in nonpregnant individuals of reproductive age.

May combine two claims.

The European Cystic Fibrosis Society Patient Registry reported an increase in CFRD with age (10% increase per decade), genotype, decreased lung function, and female sex.

“The European Cystic Fibrosis Society Patient Registry reported an increase in CFRD with age (10% increase per decade), genotype, decreased lung function, and female sex (133).”

• cites [133] Olesen, 2020, Cystic fibrosis related diabetes in Europe: prevalence, risk factors and outcome, J Cyst Fibros sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diagnosis of MODY can lead to identification of other affected family members and can indicate potential extrapancreatic complications in affected individuals.

“Additionally, diagnosis can lead to identification of other affected family members and can indicate potential extrapancreatic complications in affected individuals.”

May combine two claims.

There was a suggestion of more benefit (per prespecified subgroup analyses) among individuals who had the OGTT at less than 14 weeks and among those with OGTT glycemic values in higher ranges.

“There was also a suggestion of more benefit (per prespecified subgroup analyses) among individuals who had the OGTT at <14 weeks and among those with OGTT glycemic values in higher ranges (180).”

• cites [180] Simmons, 2023, Treatment of gestational diabetes mellitus diagnosed early in pregnancy, N Engl J Med sourceNot checked — no full text of the source

May combine two claims.

A1C is not reliable for screening for GDM or for preexisting diabetes at 15 weeks of gestation or later in part from the higher red blood cell turnover in pregnancy but also from the unknown diabetes status prior to pregnancy, which could help distinguish new-onset diabetes from preexisting diabetes.

“A1C is not reliable for screening for GDM or for preexisting diabetes at 15 weeks of gestation or later in part from the higher red blood cell turnover in pregnancy but also from the unknown diabetes status prior to pregnancy, which could help distinguish new-onset diabetes from preexisting diabetes.”

• cites [181] Cavagnolli, 2015, Factors affecting A1C in non-diabetic individuals: review and meta-analysis, Clin Chim Acta sourceNot checked — no full text of the source

May combine two claims.

The one-step method identifies long-term risks of maternal prediabetes and diabetes as well as offspring glucose intolerance and adiposity.

“The one-step method identifies longterm risks of maternal prediabetes and diabetes as well as offspring glucose intolerance and adiposity.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

If the two-step approach is implemented, the incidence of GDM will likely increase markedly.

“If this approach is implemented, the incidence of GDM will likely increase markedly.”

May combine two claims.

A 2021 U.S. Preventive Services Task Force systematic review concluded that one-step versus two-step screening is associated with increased likelihood of GDM (11.5% vs. 4.9%) but without improved health outcomes.

“A 2021 U.S. Preventive Services Task Force systematic review concluded that onestep versus two-step screening is associated with increased likelihood of GDM (11.5% vs. 4.9%) but without improved health outcomes (205).”

• cites [205] Pillay, 2021Not matched

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