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)

In the paper

“On the other hand, sleep disturbances including poor sleep quality and shorter sleep duration are associated with worsening glycemic levels in type 1 diabetes (154,155).”

What the sources say

• Partly supported

  The Results (§3.2; page not provided) find that shorter sleep duration was associated with higher HbA1c only among participants with good glycemic control; the association ran in the opposite direction among those with poor control. The same section reports no association between poor sleep quality and poor glycemic control, so the sentence overgeneralizes the duration finding and does not support its poor-sleep-quality component. (LLM, conf=0.86)

  cites [154] Denic-Roberts, 2016, Subjective sleep disturbances and glycemic control in adults with long-standing type 1 diabetes: the Pittsburgh’s Epidemiology of Diabetes Complications study, Diabetes Res Clin Pract sourceExperimental — accuracy not yet measured
• Disputed

  The Discussion reports that poor sleep quality was more common in adults with long-standing type 1 diabetes, but sleep duration did not differ from controls. Crucially, it states that subjective sleep characteristics were not associated with impaired glucoregulation; the proposed relationship with HbA1c was not detectable in this study. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites [155] van Dijk, 2011, Disturbed subjective sleep characteristics in adult patients with long-standing type 1 diabetes mellitus, Diabetologia sourceExperimental — accuracy not yet measured

In the paper

“The majority of older adults with low BMI will have type 2 diabetes (9,12,13), even more so when a person's ethnicity is associated with high type 2 diabetes risk (14).”

What the sources say

• Supported

  The cited paper supports the ethnicity-related part of the sentence, rather than the separate claim that a majority of older adults with low BMI have diabetes. In “Prevalence of diabetes by age” (page not specified), it reports higher diabetes prevalence in Indian and Maltese groups and an increase beginning at lower BMI in the Indian group; the Abstract also reports a lower BMI threshold in Indian and Maltese populations than in Europeans. (LLM, conf=0.90)

  cites [14] Nakagami, 2003, Age, body mass index and type 2 diabetes-associations modified by ethnicity, Diabetologia source

In the paper

“In people with clinical features suggesting type 1 diabetes, the presence of one or more positive islet autoantibodies is highly predictive of rapid progression and severe insulin deficiency and these individuals should be considered to have type 1 diabetes, even if they did not require insulin at diagnosis (23,24).”

What the sources say

• ?Not checked — no full text of the sourcecites [23] Littorin, 1999, Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes, Diabetes Care source
• Partly supported

  The Results report that positive islet autoantibodies were more common in participants meeting the study’s criteria for type 1 diabetes (71% versus 5%), supporting their diagnostic value. But the paper says these features overlap between diabetes types and describes GADA-positive participants who took more than three years to start insulin, suggesting slow-onset autoimmune diabetes. It therefore does not support treating antibody positivity alone as highly predictive of rapid progression in every person with suggestive clinical features. (LLM, conf=0.86)

  cites [24] Lynam, 2019, Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18-50 years, BMJ Open sourceExperimental — accuracy not yet measured

In the paper

“Rapid progression to insulin treatment (<3 years) is strongly suggestive of type 1 diabetes at any age (6,8,15).”

What the sources say

• Supported

  The Conclusion (page not available) says that patients progressing to insulin within 3 years of diagnosis have a high likelihood of type 1 diabetes. The paper compares people diagnosed above and below age 30, supporting the claim’s application across ages. (LLM, conf=0.90)

  cites [6] 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 source
• Partly supported

  The Results (Optimal clinical criteria; page not available) identify time from diagnosis to insulin as the strongest individual discriminator, supporting the link between rapid insulin treatment and type 1 diabetes. But the optimal cut-off was 12 months, not three years. The Discussion (Implications for research and practice; page not available) also reports substantial misclassification among people diagnosed at age 35 or older and treated with insulin from diagnosis, so the unqualified claim that this is strongly suggestive at any age is not supported. (LLM, conf=0.88)

  cites [8] 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 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [15] Prior, 1993, C-peptide and the classification of diabetes mellitus patients in the Early Treatment Diabetic Retinopathy Study. Report number 6, Ann Epidemiol source

In the paper

“Monogenic diabetes is found in approximately 4% of those diagnosed with diabetes before the age of 30 years; the likelihood of monogenic diabetes rises to 20% where islet antibodies are negative and C-peptide secretion is maintained (18).”

What the sources say

• Supported

  The Results (Performance of the pathway, Table 2) report a 20% positive predictive value for the pathway, which selected patients with maintained C-peptide secretion and negative islet antibodies. The Conclusions give a background prevalence of 3.6%, consistent with approximately 4% among those diagnosed by age 30. (LLM, conf=0.92)

  cites [18] Shields, 2017, Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients, Diabetes Care source

In the paper

“No single clinical feature confirms type 1 diabetes in isolation (9,10).”

• Also stated in: § SECTION 17: CONCLUSION · plain

  “No single clinical feature confirms type 1 diabetes in isolation.”

What the sources say

• Supported

  The Abstract Results identify age at diagnosis as the strongest clinical discriminator, but report imperfect sensitivity and specificity rather than definitive diagnosis. The Discussion’s Principal findings explicitly say that even diabetic ketoacidosis is not useful on its own for classifying a patient as having type 1 diabetes. Together, these support the claim that a clinical feature alone does not confirm type 1 diabetes. (LLM, conf=0.88)

  cites [9] Shields, 2015, Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature, BMJ Open source
• Not checked yetcites [10] Jones AG , HillAV, TrippettPW, HattersleyAT, McDonaldTJ, ShieldsBM. The utility of clinical features and glycaemia at diagnosis in classifying young adult onset diabetes (Abstract). Published 19 September 2019. Accessed 23 August 2021. Available from www.easd.org/virtualmeeting/home.html#!resources/the-utility-of-clinical- features-and-glycaemia-at-diagnosis-in-classifying- young-adult-onset-diabetes

In the paper

“The very strong relationship between type 2 diabetes incidence and age means that even”

What the sources say

• Supported

  The Introduction says type 2 diabetes incidence rises sharply in middle and old age, making type 1 diabetes a small minority of cases. It also says clinical features such as age at diagnosis and BMI lack sufficient discriminatory power because type 1 diabetes is uncommon in older adults. (LLM, conf=0.92)

  cites [11] Thomas, 2018, Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank, Lancet Diabetes Endocrinol source

In the paper

“Although the incidence peaks in puberty and early adulthood, new-onset type 1 diabetes occurs in all age-groups and people with type 1 diabetes live for many decades after onset of the disease, such that the overall prevalence of type 1 diabetes is higher in adults than in children, justifying our focus on type 1 diabetes in adults (1).”

What the sources say

• ?Could not verify

  The Abstract reports life expectancy in a cohort with childhood-onset type 1 diabetes, which supports the surrounding point that people can live for decades after diagnosis. Neither it nor the retrieved passages compare type 1 diabetes prevalence in adults and children (searched: prevalence, adults, children, age distribution). (LLM, conf=0.73)

  cites [1] Miller, 2012, Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort, Diabetes sourceExperimental — accuracy not yet measured

In the paper

“A new and emerging issue is the development of profound insulin deficiency associated with the use of immune check-point inhibitors, which may present with hyperglycemia and diabetic ketoacidosis (DKA) (4).”

What the sources say

• Supported

  The Abstract reports insulin-dependent diabetes after checkpoint inhibitor treatment and says 59% of cases presented with ketoacidosis. The Clinical and Laboratory Features section reports rapid progression to hyperglycemia with low or undetectable C-peptide in most patients, supporting the claim of profound insulin deficiency. (LLM, conf=0.94)

  cites [4] Stamatouli, 2018, Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors, Diabetes source

In the paper

“Monogenic diabetes is found in approximately 4% of those diagnosed with diabetes before the age of 30 years; the likelihood of monogenic diabetes rises to 20% where islet antibodies are negative and C-peptide secretion is maintained (18).”

What the sources say

• Partly supported

  The Results section reports a 3.6% prevalence, approximately 4%, among patients diagnosed before age 30, but the study also restricted this group to those currently under 50. The Results section on pathway performance reports a 20% positive predictive value after screening for maintained C-peptide secretion and negative islet antibodies. The citing sentence omits the current-age restriction on the prevalence estimate. (LLM, conf=0.86)

  cites [18] Shields, 2017, Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“The majority of older adults with low BMI will have type 2 diabetes (9,12,13), even more so when a person's ethnicity is associated with high type 2 diabetes risk (14).”

What the sources say

• Partly supported

  The Discussion (Principal findings; page unavailable) says age at diagnosis is more useful than BMI for distinguishing diabetes type, and that BMI adds less than 1% to classification based on age. This supports the point that low BMI need not indicate type 1 diabetes, but the paper does not establish that a majority of older adults with low BMI have type 2 diabetes. (LLM, conf=0.78)

  cites [9] Shields, 2015, Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature, BMJ Open sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [12] Hillier, 2001, Characteristics of an adult population with newly diagnosed type 2 diabetes: the relation of obesity and age of onset, Diabetes Care source
• ?Not checked — no full text of the sourcecites [13] Westphal, 1996, The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnosed diabetic adults, Am J Med source

In the paper

“Variability exists between individuals, but the HbA 1c and blood glucose within an individual correlate over time (68).”

What the sources say

• Supported

  The Introduction (page not provided), under “Implications for Clinical Practice,” states that several studies found an individual’s mean glucose–HbA1c relationship tends to remain reasonably constant over time. This supports the claim about the within-person relationship, although the paper refers to mean glucose rather than individual glucose readings. (LLM, conf=0.91)

  cites [68] Beck, 2017, The fallacy of average: how using hba1c alone to assess glycemic control can be misleading, Diabetes Care source

In the paper

“In some instances, the use of an implanted sensor can help avoid skin reactions in those who are sensitive to tape (84,85).”

What the sources say

• Partly supported

  The Discussion (page unavailable) says skin reactions with the implanted Eversense system were less clinically significant than allergic contact dermatitis reported with some transcutaneous systems. But the Results report adhesive-patch irritation in 20 patients, and the paper does not establish that the system helps people sensitive to tape avoid skin reactions. (LLM, conf=0.82)

  cites [84] Deiss, 2020, Real-world safety of an implantable continuous glucose sensor over multiple cycles of use: a post-market registry study, Diabetes Technol Ther sourceExperimental — accuracy not yet measured
• Partly supported

  The discussion (page unavailable) attributes a low rate of skin reactions to the implanted system’s short-duration adhesive use, and the Safety results report patch or adhesive irritation in 2.5% of users. The paper does not report outcomes specifically for people sensitive to tape, so the claim’s application to that group is not directly supported. (LLM, conf=0.82)

  cites [85] Sanchez, 2019, Real-world data from the first u.s. commercial users of an implantable continuous glucose sensor, Diabetes Technol Ther sourceExperimental — accuracy not yet measured

In the paper

“Routine C-peptide testing in those with clinically diagnosed type 1 diabetes of at least 3 years duration has led to reclassification in 11% of those with adult-onset diabetes (31).”

What the sources say

• Partly supported

  The Results passage in our copy reports routine C-peptide testing in people with a clinician-diagnosis of type 1 diabetes of at least 3 years’ duration and reclassification in 58 of 859 tested individuals (6.8%). It does not report an 11% reclassification rate for the adult-onset subgroup; searches for that figure and subgroup found no supporting passage. The overall 6.8% figure does not, by itself, contradict a possible subgroup rate. (LLM, conf=0.83)

  cites [31] Foteinopoulou, 2021, Impact of routine clinic measurement of serum C-peptide in people with a clinician-diagnosis of type 1 diabetes, Diabet Med sourceExperimental — accuracy not yet measured

In the paper

“As monogenic diabetes was less likely to have been considered in the past, molecular genetic testing for neonatal diabetes should be considered for all people with type 1 diabetes, regardless of current age, who were diagnosed under 6 months of age as more than 80% have monogenic neonatal diabetes, and the 30-50% with ATP-sensitive potassium (K ATP ) channel mutations can replace insulin with sulf”

What the sources say

• Supported

  The Methods (Patients; page unavailable) specify that all 1020 tested patients were diagnosed with diabetes before 6 months of age. The Results (page unavailable) report that a genetic cause of neonatal diabetes was identified in 840 of them (82%), supporting the claim’s ‘more than 80%’ figure for this cohort. (LLM, conf=0.92)

  cites [32] De Franco, 2015, The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study, Lancet source
• Partly supported

  The introductory passage (page not provided) says KCNJ11 mutations account for 30–58% of permanent diabetes diagnosed before six months of age. The paper also recommends genetic testing for everyone diagnosed before six months, regardless of current age. Neither passage establishes the claimed figure that more than 80% have monogenic neonatal diabetes. (LLM, conf=0.82)

  cites [33] Pearson, 2006, Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Although HbA 1c is an indicator of mean glucose, it does not inform glycemic variability and hypoglycemia and, therefore, is inappropriate as the only method of glucose evaluation in type 1 diabetes (68,69).”

What the sources say

• Supported

  The Introduction (page unavailable) shows that four patients with type 1 diabetes had the same HbA1c but markedly different glucose profiles, and explains that CGM reveals glycemic variability and hypoglycemia that HbA1c does not. The Conclusions (page unavailable) say that assessing an individual’s glycemic control from HbA1c alone can be misleading and recommend knowing the patient’s actual glucose levels. (LLM, conf=0.92)

  cites [68] Beck, 2017, The fallacy of average: how using hba1c alone to assess glycemic control can be misleading, Diabetes Care source
• ?Not checked — no full text of the sourcecites [69] Beck, 2019, The relationships between time in range, hyperglycemia metrics, and HbA1c, J Diabetes Sci Technol source

In the paper

“Furthermore, antibodies may disappear over time (26).”

What the sources say

• Supported

  The Conclusions state that antibody positivity can be lost over time and report a decline in GADA positivity after diagnosis. This supports the hedged claim that antibodies may disappear over time. (LLM, conf=0.92)

  cites [26] Tridgell, 2011, Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database, Diabetes Care source

In the paper

“TIR is associated with microvascular complications (45,46), and a TIR of 70% roughly corresponds to an HbA 1c of 53 mmol/mol (7.0%).”

What the sources say

• Supported

  The Conclusions state that TIR was strongly associated with the risk of retinopathy and microalbuminuria in the DCCT cohort. The citation is attached to the microvascular-complications claim, not the separate statement about a TIR of 70% and HbA1c. (LLM, conf=0.95)

  cites [45] Beck, 2019, Validation of time in range as an outcome measure for diabetes clinical trials, Diabetes Care source
• ?Not checked — no full text of the sourcecites [46] Ranjan, 2020, Improved time in range over 1 year is associated with reduced albuminuria in individuals with sensor-augmented insulin pump-treated type 1 diabetes, Diabetes Care source

In the paper

“Trials have demonstrated that the latest basal analogs may cause less hypoglycemia than first-generation basal analogs and NPH insulin, while rapid-acting analogs achieve better mealtime coverage and less post-meal hypoglycemia than short-acting (regular) human insulin (87,88).”

What the sources say

• Partly supported

  The Introduction reports that the second-generation basal analog Gla-300 had reduced hypoglycaemia compared with first-generation Gla-100, and the Discussion describes a reduced risk of severe hypoglycaemia in that comparison. The paper does not provide a comparison with NPH insulin, so it supports only part of the basal-insulin claim. (LLM, conf=0.87)

  cites [87] Danne, 2020, Lower risk of severe hypoglycaemia with insulin glargine 300 U/mL versus glargine 100 U/mL in participants with type 1 diabetes: a meta-analysis of 6-month phase 3 clinical trials, Diabetes Obes Metab sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion reports less hypoglycemia with insulin degludec than with first-generation insulin glargine U100 in patients with type 1 diabetes. It compares the size of that reduction with findings from a separate meta-analysis of glargine or detemir versus NPH, but SWITCH 1 did not directly compare degludec with NPH. The paper therefore supports the first-generation-analog comparison, not the full comparison attributed to it. (LLM, conf=0.83)

  cites [88] Lane, 2017, Effect of insulin degludec vs insulin glargine u100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial, JAMA sourceExperimental — accuracy not yet measured

In the paper

“As monogenic diabetes was less likely to have been considered in the past, molecular genetic testing for neonatal diabetes should be considered for all people with type 1 diabetes, regardless of current age, who were diagnosed under 6 months of age as more than 80% have monogenic neonatal diabetes, and the 30-50% with ATP-sensitive potassium (K ATP ) channel mutations can replace insulin with sulf”

What the sources say

• Partly supported

  The Discussion reports that about 40% of the neonatal-diabetes cohort had potassium-channel mutations and that most of those patients achieved improved glycaemic control after switching from insulin to sulfonylureas. The cited 30–50% range therefore describes the proportion with mutations, not the proportion of mutation carriers who can replace insulin, as the quoted claim states. (LLM, conf=0.86)

  cites [32] De Franco, 2015, The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study, Lancet sourceExperimental — accuracy not yet measured
• Supported

  The Abstract reports that KCNJ11 mutations account for 30–58% of diabetes diagnosed under six months of age, consistent with the cited 30–50% approximation. It also reports that 44 of 49 patients with Kir6.2 mutations successfully discontinued insulin after receiving sulfonylureas; the Discussion describes this as a successful switch for most patients, not all. (LLM, conf=0.89)

  cites [33] Pearson, 2006, Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations, N Engl J Med source

In the paper

“However, even with frequent BGM, most people with type 1 diabetes will have undetected and an unacceptable high frequency of hyper-and hypoglycemia (72).”

What the sources say

• Partly supported

  The Results report frequent fingerstick testing (about nine times daily), substantial hyperglycemia and more than two hours per day of hypoglycemia among subjects with type 1 diabetes. The discussion says nocturnal hypoglycemia often goes undetected by standard monitoring and postprandial hyperglycemia is underappreciated by conventional monitoring. But the paper describes these patterns in an intensively managed study cohort; it does not establish that most people with type 1 diabetes experience both at this frequency. (LLM, conf=0.85)

  cites [72] Bode, 2005, Glycemic characteristics in continuously monitored patients with type 1 and type 2 diabetes: normative values, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“In several conditions, however, HbA 1c does not reflect mean glucose; these are mainly situations where erythrocyte turnover is altered or in the presence of hemoglobinopathies (Table 4) (67).”

What the sources say

• Partly supported

  The FALSELY LOWERED A1C and FALSELY ELEVATED A1C sections explain that altered red-cell turnover can make HbA1c misrepresent average glycemia. The HEMOGLOBIN VARIANTS section says variants can also distort HbA1c, but qualifies the claim: measurement can be used for heterozygous variants when an appropriate assay is used. The citing sentence overgeneralizes the hemoglobinopathy part. (LLM, conf=0.87)

  cites [67] Radin, 2014, Pitfalls in hemoglobin A1c measurement: when results may be misleading, J Gen Intern Med sourceExperimental — accuracy not yet measured

In the paper

“The absence of autoantibodies does not exclude type 1 diabetes, since approximately 5-10% of White European people with new-onset type 1 diabetes have negative islet antibodies (8,9,25), and further consideration of the diagnosis is necessary.”

What the sources say

• ?Could not verify

  The Results describe white European patients who had diabetes for at least five years, not people with new-onset diabetes. The Discussion (Implications for research and practice) proposes studies using islet antibodies at diagnosis, but gives no estimate of how often people with new-onset type 1 diabetes test negative. Searches for antibody-negative cases and the 5–10% figure found no supporting passage in our copy. (LLM, conf=0.75)

  cites [8] 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 sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Methods (Inclusion and exclusion criteria; page unavailable) say that studies examining islet autoantibodies alone were excluded. The Discussion (Implications and future work; page unavailable) mentions antibodies as a possible diagnostic test but gives no estimate for antibody-negative, newly diagnosed White European patients. Searches for the 5–10% figure and antibody-negative type 1 diabetes found no supporting passage in our copy. (LLM, conf=0.76)

  cites [9] Shields, 2015, Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature, BMJ Open sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites [25] Thomas, The absence of islet autoantibodies in clinically diagnosed older-adult onset type 1 diabetes suggests an alternative pathology, advocating for routine testing in this age group, medRxiv

In the paper

“The absence of autoantibodies does not exclude type 1 diabetes, since approximately 5-10% of White European people with new-onset type 1 diabetes have negative islet antibodies (8,9,25), and further consideration of the diagnosis is necessary.”

What the sources say

• ?Could not verify

  The Introduction and Abstract Method define type 1 diabetes using insulin deficiency and treatment history, but do not report whether patients lacked autoantibodies. The Discussion (Implications for research and practice; page unavailable) proposes studying islet antibodies to improve diagnosis, without saying whether a negative result excludes type 1 diabetes. Searches for antibody-negative type 1 diabetes and antibody-test sensitivity found no passage addressing the claim. (LLM, conf=0.72)

  cites [8] 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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Background (page unavailable) describes islet autoantibodies as imperfect measures for distinguishing type 1 from type 2 diabetes, which supports caution about using them to rule out type 1 diabetes. The paper does not state that an antibody-negative result fails to exclude type 1 diabetes, or give the citing sentence’s 5–10% figure; its Methods say antibody-only studies were excluded. (LLM, conf=0.78)

  cites [9] Shields, 2015, Can clinical features be used to differentiate type 1 from type 2 diabetes? A systematic review of the literature, BMJ Open sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites [25] Thomas, The absence of islet autoantibodies in clinically diagnosed older-adult onset type 1 diabetes suggests an alternative pathology, advocating for routine testing in this age group, medRxiv

In the paper

“Although widely used, the available evidence on the safety and effectiveness of diabetes health apps remains limited, with issues ranging from inadequate evidence on app accuracy and clinical validity to lack of training provision, poor interoperability and standardization, and insufficient data security (65).”

What the sources say

• Supported

  The ‘Issues faced by the diabetes community’ section (pp. 6–7) says studies of diabetes app interventions are extremely limited in quantity and quality and calls for stronger evidence of lasting effectiveness. The same section discusses gaps in evidence on accuracy and clinical validity (p. 7), training and standardisation (pp. 7–8), and data-security risks (p. 9), supporting the issues listed in the citing sentence. (LLM, conf=0.94)

  cites [65] Fleming, 2020, Diabetes digital app technology: benefits, challenges, and recommendations. A consensus report by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) Diabetes Technology Working Group, Diabetologia source

In the paper

“The importance of glycemic management was demonstrated convincingly by the DCCT (39) and the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study (40).”

What the sources say

• ?Not checked — no full text of the sourcecites [39] 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 source
• Supported

  The Abstract reports that intensive therapy during the DCCT had beneficial effects on cardiovascular disease in people with type 1 diabetes that persisted through 30 years of follow-up. The introductory passage also reports reduced progression of microvascular complications during EDIC, supporting the cited point about the importance of glycemic management. (LLM, conf=0.94)

  cites [40] The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group, 2016, Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: the DCCT/EDIC study 30-year follow-up, Diabetes Care source

In the paper

“In registry studies, increased testing frequency is associated with lower HbA 1c (71).”

What the sources say

• Supported

  The Results report that more self-monitoring blood glucose measurements per day were strongly associated with lower HbA1c across all age groups in the T1D Exchange clinic registry. The Conclusions describe this as an association, not a causal effect, consistent with the citing sentence. (LLM, conf=0.95)

  cites [71] 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 source

In the paper

“None of these are as well associated with diabetes complications as HbA 1c (70).”

What the sources say

• Partly supported

  The Glycated Proteins section (page unavailable) says evidence linking fructosamine and glycated albumin to long-term outcomes was insufficient, and the Conclusion (page unavailable) calls HbA1c the key biomarker while saying long-term complication associations for alternative markers need further study. The paper also reports associations of all three alternatives with microvascular complications, but it does not establish that each is less strongly associated with complications than HbA1c. (LLM, conf=0.82)

  cites [70] Krhač, 2019, Update on biomarkers of glycemic control, World J Diabetes sourceExperimental — accuracy not yet measured

In the paper

“There is a strong correlation (r 5 >0.9) between HbA 1c and mean blood glucose levels during the preceding 3 months when glucose levels are stable (66).”

What the sources say

• Supported

  The Results report an A1C–average glucose relationship over the preceding 3 months with R² = 0.84, equivalent to r ≈ 0.92. The Research Design and Methods section required diabetic participants to have stable glycemic control before recruitment and excluded conditions likely to cause a major change in glycemia. (LLM, conf=0.91)

  cites [66] Nathan, 2008, Translating the A1C assay into estimated average glucose values, Diabetes Care source

In the paper

“In the U.S., inhaled human insulin is an alternative to subcutaneous rapid-acting analogs (3).”

What the sources say

• Supported

  The Rapid-acting Analog Insulins section says Afrezza is inhaled recombinant human regular insulin and was the only inhaled insulin on the U.S. market. It contrasts Afrezza with rapid-acting analog insulins, supporting its description as an alternative to subcutaneous rapid-acting analogs. (LLM, conf=0.93)

  cites [3] Hirsch, 2020, The evolution of insulin and how it informs therapy and treatment choices, Endocr Rev source

In the paper

“However, independent of other risk factors and comorbidities, more episodes of severe hypoglycemia were associated with greater decrements in psychomotor and mental efficiency that were most notable after 32 years of follow-up (110).”

What the sources say

• Supported

  The Results (page not supplied) report that, after adjustment for other covariates, severe hypoglycemia was independently associated with declining psychomotor and mental efficiency; they also report a dose-response relationship as episodes increased. The Results show a substantially larger decline between years 18 and 32 than before year 18, and the Discussion notes that an association with severe hypoglycemia had not been found at the earlier assessments. (LLM, conf=0.94)

  cites [110] Jacobson, 2021, Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study, Lancet Diabetes Endocrinol source

In the paper

“Since this is highly variable between individuals, postprandial glucose measurements for up to 3 h or more may be needed to determine initial dose adjustments (134).”

What the sources say

• Supported

  In “How should nutrition therapy vary based on type and intensity of insulin plan?” (p. 12), the report says responses to high-fat or high-protein mixed meals differ among individuals and delayed hyperglycemia may occur 3 hours or more after eating. It says checking glucose 3 hours after eating may help determine whether insulin adjustments are needed and that glucose monitoring should guide dose adjustments. (LLM, conf=0.87)

  cites [134] Evert, 2019, Nutrition therapy for adults with diabetes or prediabetes: a consensus report, Diabetes Care source

In the paper

“The pathophysiology of IAH is still not fully understood but includes a partial or total loss of sympathoadrenal reactions to hypoglycemia that prevent catecholaminergic stimulation of hepatic glucose output and restraint of muscle glucose uptake (104).”

What the sources say

• Partly supported

  The Summary (page unavailable) identifies attenuated sympathoadrenal responses as central to hypoglycemia-associated autonomic failure and says that a reduced epinephrine response causes defective glucose counterregulation. The Compromised Defenses section links this process to hypoglycemia unawareness and increased glucose production, but our copy does not establish total loss of the response or the claimed restraint of muscle glucose uptake. (LLM, conf=0.85)

  cites [104] Cryer, 2013, Mechanisms of hypoglycemia-associated autonomic failure in diabetes, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Sleep may be disrupted in people with type 1 diabetes as a result of both behavioral and physiological aspects of diabetes and its management (153).”

What the sources say

• Supported

  The Discussion (page not supplied) says that nocturnal hypoglycemia can disrupt sleep and that nighttime diabetes care can affect time in bed or sleep duration. It also identifies neuropathic pain and psychological factors as possible contributors to poor sleep quality in type 1 diabetes. This supports the claim's hedged description of physiological and behavioral factors. (LLM, conf=0.92)

  cites [153] Reutrakul, 2016, Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis, Sleep Med source

In the paper

“Several clinical trials have not shown a reduction of IAH by using CGM despite a reduced incidence of level 3 hypoglycemia (101,112,124,126-128).”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Heinemann, 2018, Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial, Lancet source
• Supported

  The Clinical Trials section (page unavailable) reports that HypoDE had 64% fewer severe hypoglycemic episodes with CGM but no difference in awareness improvement between the CGM and self-monitoring groups. It also reports no CGM-specific awareness benefit in HypoCOMPaSS, despite reduced hypoglycemia across its study arms. The claim is supported as a statement about the absence of a demonstrated CGM-specific reduction in IAH, not an absence of improvement in awareness within any group. (LLM, conf=0.86)

  cites [112] Lin, 2020, Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies, J Diabetes Investig source
• ?Not checked — no full text of the sourcecites [124] Cranston, 1994, Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes, Lancet source
• ?Could not verify

  The Multicenter Trials and Hypoglycemia Anticipation, Awareness, and Treatment Training sections (pages unavailable) discuss BGAT and HAATT, not CGM trials. Searches for continuous glucose monitoring, impaired hypoglycemia awareness, and severe hypoglycemia found no passage addressing whether CGM reduces IAH despite reducing level 3 hypoglycemia. (LLM, conf=0.76)

  cites [126] Cox, 2006, Blood glucose awareness training: what is it, where is it, and where is it going?, Diabetes Spectr sourceExperimental — accuracy not yet measured
• Partly supported

  The Conclusions state that RT-CGM has been found effective in preventing severe hypoglycemia. They do not say that CGM trials failed to reduce impaired hypoglycemia awareness (IAH), or report that pattern across several trials. This paper’s own trial tested HypoAware, not CGM. (LLM, conf=0.83)

  cites [127] Rondags, 2016, Effectiveness of HypoAware, a brief partly web-based psychoeducational intervention for adults with type 1 and insulin-treated type 2 diabetes and problematic hypoglycemia: a cluster randomized controlled trial, Diabetes Care sourceExperimental — accuracy not yet measured
• Partly supported

  The HyPOS study reports fewer severe hypoglycemic episodes in its education-program group than in the control group at 31 months (main text; page unavailable). It does not study CGM or report that CGM trials failed to reduce impaired awareness of hypoglycemia. The main text instead notes improved awareness after six months of HyPOS. (LLM, conf=0.83)

  cites [128] Hermanns, 2010, Long-term effect of an education program (HyPOS) on the incidence of severe hypoglycemia in patients with type 1 diabetes, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“Hybrid closedloop systems are the most effective means of maintaining glucose in the normal range in people with type 1 diabetes (90,91).”

What the sources say

• ?Not checked — no full text of the sourcecites [90] Bergenstal, 2016, Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes, JAMA source
• Partly supported

  The Results (p. 1) show that the closed-loop group spent more time in the target glucose range than the sensor-augmented pump group. But the trial compared one closed-loop system with one alternative; it does not establish that hybrid closed-loop systems are the most effective means among all options. (LLM, conf=0.88)

  cites [91] Brown, 2019, Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“HbA 1c , TIR, and TBR are improved further when physiological MDI or pump regimens are augmented with CGM usage (89), with the greatest benefits seen with algorithm-driven automated basal (and in some systems correction) insulin delivery, which is commonly called hybrid closed-loop therapy (90,91).”

What the sources say

• ?Not checked — no full text of the sourcecites [90] Bergenstal, 2016, Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes, JAMA source
• Supported

  The Discussion (p. 9) reports that, in this six-month type 1 diabetes trial, closed-loop therapy improved time in range, hyperglycemia, hypoglycemia, and glycated hemoglobin compared with a pump using CGM alone. The paper describes the system’s automated basal adjustments and correction boluses (p. 2), supporting the cited sentence’s description of hybrid closed-loop therapy. (LLM, conf=0.90)

  cites [91] Brown, 2019, Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes, N Engl J Med source

In the paper

“Structured education programs, such as Dose Adjustment For Normal Eating (DAFNE) and blood glucose awareness training (BGAT), which provide informed support for active insulin dose self-adjustment, are the key to the prevention of hypoglycemia and lead to sustained falls in level 3 hypoglycemia rates in those at high risk (122,123).”

What the sources say

• ?Not checked — no full text of the sourcecites [122] Little, 2018, Sustained reduction in severe hypoglycemia in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia: two-year follow-up in the HypoCOMPaSS randomized clinical trial, Diabetes Care source
• Partly supported

  The DTTP-based programmes section reports about a 50% reduction in severe hypoglycaemia after DAFNE at one-year follow-up. The BGAT section and comparison table report a substantial reduction in a Swiss BGAT study followed for 12 months, where people with recurrent severe hypoglycaemia were encouraged to participate. However, the paper does not establish sustained reductions specifically in high-risk participants for both programmes: the DAFNE follow-up was not restricted to that group, and the Swiss BGAT study enrolled an unselected type 1 diabetes population. (LLM, conf=0.84)

  cites [123] Iqbal, 2018, The role of structured education in the management of hypoglycaemia, Diabetologia sourceExperimental — accuracy not yet measured

In the paper

“If an individual has proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy, then vigorous activity requiring straining may be contraindicated because of the risk of vitreous hemorrhage or retinal detachment (151).”

What the sources say

• Partly supported

  The Diabetes-related complications section (page not supplied) says vigorous exercise and heavy weight lifting are contraindicated in certain people with long-standing diabetes or HbA1c well above target, particularly those with unstable proliferative retinopathy. It does not address severe nonproliferative retinopathy or identify vitreous hemorrhage or retinal detachment as the reason for the restriction. (LLM, conf=0.88)

  cites [151] Riddell, 2017, Exercise management in type 1 diabetes: a consensus statement, Lancet Diabetes Endocrinol sourceExperimental — accuracy not yet measured

In the paper

“Those responding, “less than 3.0 mmol/L (54 mg/dL)” or not experiencing symptoms have a >4-fold increased risk of level 3 hypoglycemia (120).”

What the sources say

• Partly supported

  The Results section (‘Changes in self-reported hypoglycemia awareness’; page unavailable) defines impaired awareness as symptom onset below 3 mmol/L or no symptoms and reports a higher frequency of severe hypoglycemia in that group. It says the frequency was more than threefold higher, not that the risk was more than fourfold higher. (LLM, conf=0.88)

  cites [120] Hopkins, 2012, Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“Self-reported awareness, however, agrees well with the autonomic glucose threshold (116).”

What the sources say

• Supported

  The Results and Conclusions state that a composite self-report measure agreed reasonably well with the physiological classification based on autonomic symptoms during experimental hypoglycemia. The paper describes the agreement as reasonable rather than strong. (LLM, conf=0.88)

  cites [116] Janssen, 2000, Assessing impaired hypoglycemia awareness in type 1 diabetes: agreement of self-report but not of field study data with the autonomic symptom threshold during experimental hypoglycemia, Diabetes Care source

In the paper

“Adjunctive use of sodium-glucose cotransporter (SGLT) inhibitors (see below) in adults with type 1 diabetes increases the risk of DKA by an absolute rate of about 4% per year, suggesting the need for intensive diabetes self-management education and monitoring (216,217).”

What the sources say

• Supported

  The Conclusions state that, in clinical trials, the absolute increase in DKA risk for SGLT inhibitor–treated patients versus placebo-treated patients was about 4% per year. The paper also calls for strategies to mitigate that risk, consistent with the citing sentence’s recommendation for monitoring and education. (LLM, conf=0.94)

  cites [216] Danne, 2019, International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors, Diabetes Care source
• ?Not checked — no full text of the sourcecites [217] Goldenberg, 2019, Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol, Diabetes Obes Metab source

In the paper

“Psychological distress, including mild to major depression, is a risk factor for poor self-care, hyperglycemia, complications, and excess mortality (174-176).”

What the sources say

• ?Not checked — no full text of the sourcecites [174] Snoek, 2015, Constructs of depression and distress in diabetes: time for an appraisal, Lancet Diabetes Endocrinol source
• Partly supported

  The sections “Mechanisms linking depression and diabetes” and “Depression in diabetes and long-term health outcomes” link depression in people with diabetes to poorer self-care, complications, and higher mortality. They describe hyperglycaemia as part of a hypothesized mechanism, not as an established outcome of psychological distress, and do not establish the claimed range from mild to major depression. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites [175] Pouwer, 2020, How 25 years of psychosocial research has contributed to a better understan ding of the links between depression and diabetes, Diabet Med sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [176] Fisher, 2016, Prevalence of depression in type 1 diabetes and the problem of over-diagnosis, Diabet Med source

In the paper

“Regardless of the b-cell replacement approach (pancreas or islets), the majority of recipients experience reliable prevention of problematic hypoglycemia with near-normal glycemic levels.”

What the sources say

• Supported

  The TRANSPLANT INTERVENTIONS section says that, regardless of whether recipients receive a pancreas or islet transplant, the majority can anticipate relief from problematic hypoglycemia for at least five years alongside near-normal glycemic control. It also describes reliable protection from severe hypoglycemia. (LLM, conf=0.94)

  cites [242] Choudhary, 2015, Evidence-informed clinical practice recommenda tions for treatment of type 1 diabetes complicated by problematic hypoglycemia, Diabetes Care source

In the paper

“Careful patient selection and protocol optimization have led to substantial clinical improvements (224).”

What the sources say

• Partly supported

  The Results describe changes in recipient selection and transplantation protocols, and the Conclusions report better outcomes in 2007–2010 than in 1999–2006. The paper does not establish that those changes caused the improvements: its Statistics section says comparisons across eras were not randomized, and the Conclusions describe the potential benefit of newer immunosuppression strategies as a possibility. (LLM, conf=0.84)

  cites [224] Barton, 2012, Improvement in outcomes of clinical islet transplantation: 1999-2010, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“The association between generalized anxiety and suboptimal blood glucose levels is less clear (177,178).”

What the sources say

• ?Not checked — no full text of the sourcecites [177] Sultan, 2008, A longitudinal study of coping, anxiety and glycemic control in adults with type 1 diabetes, Psychol Health source
• ?Could not verify

  The available passages labeled Abstract contain bibliographic information but no findings about blood glucose levels. Searches for generalized anxiety, glycemic control, and HbA1c found no passage addressing whether that association is unclear. (LLM, conf=0.72)

  cites [178] Nefs, 2019, Comorbid elevated symptoms of anxiety and depression in adults with type 1 or type 2 diabetes: results from the international diabetes MILES study, J Diabetes Complications sourceExperimental — accuracy not yet measured

In the paper

“Islet and pancreas transplants are the only approaches to date that confer both sustained recovery from IAH and restoration of glucose counterregulation and, thereby, reliable protection from level 3 hypoglycemia in people with long-standing type 1 diabetes (242).”

What the sources say

• Supported

  The Transplant Interventions section says islet and pancreas transplants are the only approaches to date that provide sustained recovery from hypoglycemia-associated autonomic failure and restored glucose counterregulation, thereby reliably protecting against severe hypoglycemia in patients with long-standing type 1 diabetes. The same section describes normalized symptom responses and recovered hypoglycemia recognition, supporting the claim’s wording about impaired awareness. (LLM, conf=0.91)

  cites [242] Choudhary, 2015, Evidence-informed clinical practice recommenda tions for treatment of type 1 diabetes complicated by problematic hypoglycemia, Diabetes Care source

In the paper

“DKA in the setting of SGLT inhibitor use is often so-called euglycemic DKA, with initial case reports describing admission glucose levels of 5.3-12.4mmol/L (96-224 mg/dL) (218).”

What the sources say

• Partly supported

  The Results table and Conclusions describe euglycemic DKA associated with SGLT-2 inhibitor use. But the stated admission-glucose range is not accurate for these cases: the 96 mg/dL event was treated as an outpatient, while the table lists a presenting glucose of 233 mg/dL (12.9 mmol/L) for another case. (LLM, conf=0.89)

  cites [218] Peters, 2015, Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“While no risk mitigation strategies have been proven to lower the risk of DKA, a consensus statement on SGLT2 inhibitors and DKA suggested careful patient selection, appropriate insulin dose adjustment to avoid insulinopenia, starting with a low dose of SGLT2 inhibitors, and regular ketone measurements with prompt action to address elevated values as sensible precautions aimed at preventing DKA (”

What the sources say

• Partly supported

  The Patient Selection, Insulin Dose Adjustments, Initiation and Dosing, and Ketone Monitoring sections recommend the precautions listed in the citing sentence. The Research Questions section says there is no evidence that daily ketone monitoring prevents DKA, but does not establish the broader claim that no risk-mitigation strategy has been proven to lower risk. The Initiation and Dosing section also reports lower DKA rates with lower SGLT inhibitor doses in clinical trials. Page numbers were not available in our copy. (LLM, conf=0.84)

  cites [216] Danne, 2019, International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors, Diabetes Care sourceExperimental — accuracy not yet measured

In the paper

“Insulin independence can be maintained for 5 years in 50% of recipients (236,237).”

What the sources say

• Partly supported

  The Results report 50% insulin independence at five years in two groups of islet transplant recipients given potent induction immunotherapy. The citing sentence omits that treatment condition, so the 50% figure is not established for islet transplant recipients generally. (LLM, conf=0.85)

  cites [236] Bellin, 2012, Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes, Am J Transplant sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and Discussion report a 50% five-year insulin-independence rate in another study, but that rate applies to patients receiving particular immunosuppressive regimens. This paper’s own UIC cohort had a 60% rate at five years, so it does not establish 50% as a general rate for islet transplant recipients. (LLM, conf=0.84)

  cites [237] Qi, 2014, Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience, Acta Diabetol sourceExperimental — accuracy not yet measured

In the paper

“Lack of social support or feeling “policed” by family, friends, or coworkers also evokes emotional distress in individuals with type 1 diabetes (170).”

What the sources say

• Partly supported

  The ‘Diabetes in youth’ section links family conflict and peer relationships to psychosocial outcomes in adolescents with type 1 diabetes; the work-life section reports work-related distress in people with type 1 diabetes. The paper does not specifically describe feeling ‘policed’ by family, friends, or coworkers, or establish that those interactions evoke emotional distress across individuals with type 1 diabetes. (LLM, conf=0.84)

  cites [170] de Wit, 2020, State of the art: understanding and integration of the social context in diabetes care, Diabet Med sourceExperimental — accuracy not yet measured

In the paper

“Trials in people with type 2 diabetes have shown convincing reductions in cardiovascular events with some GLP-1 RA (259); whether these benefits would also be seen in people with type 1 diabetes is unknown.”

What the sources say

• Supported

  The Conclusion reports significant reductions in composite cardiovascular outcomes with liraglutide, subcutaneous semaglutide, albiglutide and dulaglutide in patients with type 2 diabetes. It also distinguishes these agents from others that showed non-inferiority but not superiority, matching the claim’s qualification of “some” GLP-1 RAs. (LLM, conf=0.94)

  cites [259] Sheahan, 2020, An overview of GLP-1 agonists and recent cardiovascular outcomes trials, Postgrad Med J source

In the paper

“The largest study to date assessed the use of metformin 1 g, twice daily, in 428 people with type 1 diabetes who were treated for 3 years, with a primary end point of changes in mean carotid intima-media thickness, a marker of cardiovascular disease risk.”

What the sources say

• Supported

  The Results report 428 participants with type 1 diabetes randomised to metformin or placebo; the Methods specify metformin 1000 mg twice daily for 3 years and identify progression of averaged mean far-wall cIMT as the primary outcome. The Discussion describes the previous longest trial as involving 100 participants for 1 year, supporting the description of REMOVAL as the largest study to date. The 428 participants were in both trial arms, not all assigned metformin. (LLM, conf=0.93)

  cites [246] Petrie, 2017, Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial, Lancet Diabetes Endocrinol source

In the paper

“the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) showed that when CGM was used in conjunction with BGM, CGM was associated with better pregnancy outcomes (266)”

What the sources say

• Supported

  The Abstract Findings describe a comparison of capillary glucose monitoring with CGM versus capillary glucose monitoring without CGM in pregnant women with type 1 diabetes. They report significantly improved neonatal outcomes in the CGM group, including fewer large-for-gestational-age infants and fewer neonatal intensive care admissions. (LLM, conf=0.93)

  cites [266] Feig, 2017, Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial, Lancet source

In the paper

“People with type 1 diabetes, particularly those with concomitant chronic kidney disease, are at higher risk of hypoglycemia, which should be avoided by careful insulin and carbohydrate matching (129).”

What the sources say

• Partly supported

  The Conventional Risk Factors section identifies reduced insulin clearance in renal failure as a hypoglycemia risk factor, and the Summary of Recommendations advises matching insulin action to glucose availability to avoid hypoglycemia. The paper does not extend the renal-failure finding to all chronic kidney disease, so the claim's broader CKD qualifier is not fully supported. No page numbers are available in our copy. (LLM, conf=0.84)

  cites [129] Cryer, 2010, Hypoglycemia in type 1 diabetes mellitus, Endocrinol Metab Clin North Am sourceExperimental — accuracy not yet measured

In the paper

“and in people with gastroparesis and unpredictable rates of food absorption (277).”

What the sources say

• Partly supported

  The Introduction describes delayed solid-food transit in people with type 1 diabetes and gastroparesis. The Discussion says that a mismatch between food transit or absorption and insulin action can affect glycemic control, but it does not establish that absorption rates are unpredictable or extend that finding to all people with gastroparesis. Page numbers are unavailable in our copy. (LLM, conf=0.78)

  cites [277] Aleppo, 2017, Reported gastroparesis in adults with type 1 diabetes (T1D) from the T1D Exchange clinic registry, J Diabetes Complications sourceExperimental — accuracy not yet measured

In the paper

“Misclassification of type 1 diabetes in adults is common, and over 40% of those developing type 1 diabetes after age 30 years are initially treated as having type 2 diabetes (6)(7)(8).”

What the sources say

• ?Not matched

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

  cites (6)(7)(8)

In the paper

“Misclassification of type 1 diabetes in adults is common, and over 40% of those developing type 1 diabetes after age 30 years are initially treated as having type 2 diabetes (6)(7)(8).”

What the sources say

• ?Not matched

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

  cites (6)(7)(8)

In the paper

“Other features classically associated with type 1 diabetes, such as ketosis without acidosis, osmotic symptoms, family history, or a history of autoimmune diseases are weak discriminators (8)(9)(10).”

• Also stated in: § SECTION 17: CONCLUSION · plain

  “Other features classically associated with type 1 diabetes, such as ketosis without acidosis, osmotic symptoms, family history, or a history of autoimmune diseases are weak discriminators.”

What the sources say

• ?Not matched

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

  cites (8)(9)(10)

In the paper

“The diagnosis of type 1 diabetes can be more difficult in adults who progress to insulin therapy more slowly.”

In the paper

“Large areas of clinical practice in type 1 diabetes are based on expert opinion and cohort studies rather than RCTs and so the writing group considered both observational and clinical trial findings, rather than relying solely on unbiased RCTs and meta-analyses.”

In the paper

“The most discriminative feature is younger age at diagnosis (<35 years), with lower BMI (<25 kg/m 2 ), unintentional weight loss, ketoacidosis, and glucose >20 mmol/L (>360 mg/dL) at presentation also being informative.”

What the sources say

• ?Not matched

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

  cites (8)(9)(10)

In the paper

“Similar to the situation for blood pressure, there is a paucity of trials of lipid-lowering therapy in people with type 1 diabetes, but an observational study reported that lipid-lowering therapy is associated with a 22-44% reduction in the risk of cardiovascular disease and death among individuals with type 1 diabetes without a prior history of cardiovascular disease (48).”

In the paper

“Similar to the situation for blood pressure, there is a paucity of trials of lipid-lowering therapy in people with type 1 diabetes, but an observational study reported that lipid-lowering therapy is associated with a 22-44% reduction in the risk of cardiovascular disease and death among individuals with type 1 diabetes without a prior history of cardiovascular disease (48).”

What the sources say

• ?Not checked — no full text of the sourcecites [48] Hero, 2016, Association between use of lipid-lowering therapy and cardiovascular diseases and death in individuals with type 1 diabetes, Diabetes Care source

In the paper

“There is an absence of high-quality data to guide blood pressure targets in type 1 diabetes, but RCTs in other populations have demonstrated that treatment of hypertension to a blood pressure <140/90 mmHg reduces cardiovascular events and microvascular complications.”

In the paper

“In those aged over 35 years, type 2 diabetes becomes increasingly likely with absent islet autoantibodies and older age.”

In the paper

“In those diagnosed below the age of 35 years, type 1 diabetes is still the most likely diagnosis, particularly if there are no clinical features of type 2 diabetes or monogenic diabetes.”

In the paper

“Persistent C-peptide >600 pmol/L (nonfasting) is strongly suggestive of type 2 diabetes, and people with C-peptide in this range are often able to replace insulin with other agents (27)(28)(29)(30).”

What the sources say

• ?Not matched

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

  cites (27)(28)(29)(30)

In the paper

“Increasingly, achieving and maintaining glucose levels in the target range have become possible with fewer episodes of hypoglycemia (41)(42)(43)(44).”

What the sources say

• ?Not matched

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

  cites (41)(42)(43)(44)

In the paper

“The prevention of long-term complications of diabetes, particularly cardiovascular disease, extends beyond glycemic management to include the optimal management of blood pressure and use of lipid-lowering medication.”

In the paper

“Persistent C-peptide >600 pmol/L (nonfasting) is strongly suggestive of type 2 diabetes, and people with C-peptide in this range are often able to replace insulin with other agents (27)(28)(29)(30).”

What the sources say

• ?Not matched

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

  cites (27)(28)(29)(30)

In the paper

“Other biomarkers, such as fructosamine, 1,5-anhydroglucitol and glycated albumin, provide measures of mean glucose, albeit with shorter durations than HbA 1c .”

In the paper

“TIR is associated with microvascular complications (45,46), and a TIR of 70% roughly corresponds to an HbA 1c of 53 mmol/mol (7.0%).”

In the paper

“However, it can be hard to differentiate between type 1 diabetes and type 2 diabetes based on age and clinical features in non-White European populations.”

In the paper

“Capillary blood glucose monitoring (BGM) can help people with type 1 diabetes achieve these HbA 1c goals.”

In the paper

“Pre-COVID-19, results from a limited number of studies using telemedicine in different subgroups of people with type 1 diabetes suggested that remote monitoring, education, and provider visits have the potential to: improve outcomes, quality of life, and selfmanagement; increase access to care and reduce costs; and are well-accepted with improved treatment satisfaction (54)(55)(56)(57).”

What the sources say

• ?Not matched

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

  cites (54)(55)(56)(57)

In the paper

“Furthermore, the insulin doses needed to prevent hyperglycemia are associated with a high risk of hypoglycemia, leaving people with type 1 diabetes walking a tightrope between high and low glucose levels.”

In the paper

“Most people with type 1 diabetes can benefit from this technology with appropriate initial and ongoing education, including frequent observation of the glucose trends.”

In the paper

“People with type 1 diabetes should be warned that contact dermatitis (both irritant and allergic) may occur with all CGM devices that attach to the skin (81)(82)(83).”

What the sources say

• ?Not matched

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

  cites (81)(82)(83)

In the paper

“By contrast, low or absent C-peptide confirms the diagnosis of type 1 diabetes.”

In the paper

“It should be recognized that any reduction in HbA 1c from high initial levels has significant benefit even if the”

In the paper

“The latter may be confounded by impaired renal function.”

In the paper

“With the use of intensive insulin therapy that aimed to achieve blood glucose levels close to the nondiabetes range, HbA 1c was lowered by 2% (22 mmol/mol) to a mean HbA 1c of 7.0% (53 mmol/mol) over a mean of 6.5 years, compared with standard care (mean HbA 1c 9.0% [75 mmol/mol]) (39).”

What the sources say

• ?Not checked — no full text of the sourcecites [39] 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 source

In the paper

“Several level 3 programs have been developed for adults with type 1 diabetes and have proven to be effective, both in terms of improved glycemic outcomes and improved psychosocial outcomes (61).”

What the sources say

• Not checked yetcites [61] Diabetes UK . Diabetes self-management education. Accessed 11 February 2021. Available from www.diabetes.org.uk/professionals/resourc es/resources-to-improve-your-clinical-practice/ diabetes-self-management-education

In the paper

“There is an absence of high-quality data to guide blood pressure targets in type 1 diabetes, but RCTs in other populations have demonstrated that treatment of hypertension to a blood pressure <140/90 mmHg reduces cardiovascular events and microvascular complications.”

In the paper

“IAH increases the risk of level 3 hypoglycemia by sixfold (114)”

What the sources say

• ?Not checked — no full text of the sourcecites [114] Gold, 1994, Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia, Diabetes Care source

In the paper

“Mortality from hypoglycemia in type 1 diabetes is not trivial.”

What the sources say

• ?Not checked — no full text of the sourcecites [107] Gagnum, 2017, Causes of death in childhood-onset type 1 diabetes: long-term follow-up, Diabet Med source

In the paper

“A secondary analysis of the IN CONTROL trial, where the primary analysis showed a reduction in level 3 hypoglycemia in people using CGM, demonstrated an increase in the rate of level 3 hypoglycemia with lower HbA 1c , similar to what was reported in the DCCT (106).”

What the sources say

• ?Not checked — no full text of the sourcecites [106] van Beers, 2018, The relation between HbA1c and hypoglycemia revisited; a secondary analysis from an intervention trial in patients with type 1 diabetes and impaired awareness of hypoglycemia, J Diabetes Complications source

In the paper

“With regard to cognitive function, in the DCCT and EDIC study, after 18 years of follow-up, severe hypoglycemia in middleaged adults did not appear to affect neurocognitive function (109).”

What the sources say

• ?Not checked — no full text of the sourcecites [109] Jacobson, 2007, Long-term effect of diabetes and its treatment on cognitive function, N Engl J Med source

In the paper

“The Gold questionnaire and Clarke questionnaire, showing a score equal or above 4 are indicative of IAH (114,117)”

What the sources say

• ?Not checked — no full text of the sourcecites [114] Gold, 1994, Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia, Diabetes Care source
• ?Not checked — no full text of the sourcecites [117] Clarke, 1995, Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms, Diabetes Care source

In the paper

“Needles as short as 4 mm, injected at a 90 angle, enter the subcutaneous space with minimal risk of intramuscular injection in most adults (92).”

What the sources say

• ?Not checked — no full text of the sourcecites [92] Gibney, 2010, Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations, Curr Med Res Opin source

In the paper

“However, walking does not increase the risk of ulceration in people with peripheral neuropathy (150).”

What the sources say

• ?Not checked — no full text of the sourcecites [150] Lemaster, 2003, Daily weight-bearing activity does not increase the risk of diabetic foot ulcers, Med Sci Sports Exerc source

In the paper

“An association between recent recreational cannabis consumption and a more than twofold increased risk of DKA has been reported from countries where cannabis has been legalized, possibly related to the emergence of higher potency formulations of cannabis and other synthetic cannabinoids (138).”

What the sources say

• ?Not checked — no full text of the sourcecites [138] Pastor, 2020, Alcohol and illicit drug use in people with diabetes, Lancet Diabetes Endocrinol source

In the paper

“This implies that lowering HbA 1c may still come with a higher risk of level 3 hypoglycemia.”

In the paper

“Medical nutrition therapy delivered by a registered dietitian is associated with a reduction in HbA 1c of 1.0-1.9%(11-21 mmol/mol) for people with suboptimally managed type 1 diabetes when integrated into an overall management program (131).”

What the sources say

• ?Not checked — no full text of the sourcecites [131] American Diabetes Association, 2019, 5. Lifestyle management: Standards of Medical Care in Diabetes—2019, Diabetes Care source

In the paper

“One recent trial noted more than 8% of deaths for those younger than 56 years were from hypoglycemia (107).”

What the sources say

• ?Not checked — no full text of the sourcecites [107] Gagnum, 2017, Causes of death in childhood-onset type 1 diabetes: long-term follow-up, Diabet Med source

In the paper

“Strict avoidance of hypoglycemia can help to restore hypoglycemia awareness (124).”

What the sources say

• ?Not checked — no full text of the sourcecites [124] Cranston, 1994, Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes, Lancet source

In the paper

“Level 3 hypoglycemia is less common but occurred in 12% of adults with type 1 diabetes over a 6-month period in a recent global observational analysis (102).”

What the sources say

• ?Not matched

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

  cites [102] Renard, The SAGE study: global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM, Diabetes Metab Res Rev

In the paper

“The Pedersen-Bjergaard et al. questionnaire and Hypoglycemia Awareness Questionnaire (HypoA-Q) can also identify IAH (118,119).”

What the sources say

• ?Not checked — no full text of the sourcecites [118] Pedersen-Bjergaard, 2003, Recall of severe hypoglycaemia and self-estimated state of awareness in type 1 diabetes, Diabetes Metab Res Rev source
• ?Not checked — no full text of the sourcecites [119] Speight, 2016, Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q), Diabet Med source

In the paper

“HbA 1c , TIR, and TBR are improved further when physiological MDI or pump regimens are augmented with CGM usage (89), with the greatest benefits seen with algorithm-driven automated basal (and in some systems correction) insulin delivery, which is commonly called hybrid closed-loop therapy (90,91).”

What the sources say

• ?Not checked — no full text of the sourcecites [89] Šoupal, 2020, Glycemic outcomes in adults with T1D are impacted more by continuous glucose monitoring than by insulin delivery method: 3 years of follow-up from the COMISAIR study, Diabetes Care source

In the paper

“Carbohydrate counting and insulin:carbohydrate ratios can be a useful method for adjusting mealtime insulin dosing for optimal glycemic outcomes (132,133).”

What the sources say

• ?Not checked — no full text of the sourcecites [132] Bell, 2014, Efficacy of carbohydrate counting in type 1 diabetes: a systematic review and meta-analysis, Lancet Diabetes Endocrinol source
• ?Not checked — no full text of the sourcecites [133] Schmidt, 2014, Effects of advanced carbohydrate counting in patients with type 1 diabetes: a systematic review, Diabet Med source

In the paper

“Hypoglycemia with glucose levels below 3.0 mmol/L (54 mg/dL) occurs much more often than previously appreciated (46,101).”

What the sources say

• ?Not checked — no full text of the sourcecites [46] Ranjan, 2020, Improved time in range over 1 year is associated with reduced albuminuria in individuals with sensor-augmented insulin pump-treated type 1 diabetes, Diabetes Care source
• ?Not checked — no full text of the sourcecites [101] Heinemann, 2018, Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial, Lancet source

In the paper

“However, more recent studies have not found this to be the case (41,210,215).”

What the sources say

• ?Not checked — no full text of the sourcecites [41] Weinstock, 2013, Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry, J Clin Endocrinol Metab source
• ?Not checked — no full text of the sourcecites [210] Kalscheuer, 2019, Event rates and risk factors for the development of diabetic ketoacidosis in adult patients with type 1 diabetes: analysis from the DPV Registry based on 46,966 patients, Diabetes Care source
• ?Not checked — no full text of the sourcecites [215] Hoshina, 2018, Treatment modality-dependent risk of diabetic ketoacidosis in patients with type 1 diabetes: Danish adult diabetes database study, Diabetes Technol Ther source

In the paper

“With an SPK transplant, most recipients can expect amelioration of problematic hypoglycemia for more than a decade (229-231).”

What the sources say

• ?Not checked — no full text of the sourcecites [229] Gruessner, 2012, Long-term outcome after pancreas trans plantation, Curr Opin Organ Transplant source
• ?Not checked — no full text of the sourcecites [230] Sollinger, 2009, One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up, Ann Surg source
• ?Not checked — no full text of the sourcecites [231] Lehmann, 2015, Glycemic control in simultaneous islet-kidney versus pancreas-kidney transplantation in type 1 diabetes: a prospective 13-year follow-up, Diabetes Care source

In the paper

“Fear of hypoglycemia affects up to 10% of adults with type 1 diabetes, particularly among those experiencing repeated episodes of level 3 hypoglycemia (190).”

What the sources say

• ?Not checked — no full text of the sourcecites [190] Wild, 2007, A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education, Patient Educ Couns source