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Cited by 1,585Diabetes and associated disordersDiabetes Management and ResearchDiabetes Treatment and Management

Type 1 diabetes

Open access
DiMeglio, Linda A, Evans-Molina, Carmella, Oram, Richard A·2018·The Lancet
DOI 10.1016/s0140-6736(18)31320-5PMC PMC6661119
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Abstract

Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(18)31320-5

Cites

177 of 177 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

73 of 121 cited sources checked · 29 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    A cure for type 1 diabetes remains elusive.

    “a cure for type 1 diabetes remains elusive.1,2”
    • Also stated in: § Introduction · plain
      “Although survival and patient health have improved considerably, particularly in the past 25 years, a cure for type 1 diabetes remains elusive.1,2”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [1] Barnett, 2018, Type 1 diabetes, Lancet source
    • cites [2] Skyler, 2018, Hope vs hype: where are we in type 1 diabetes?, Diabetologia source
  • Premisecitation

    At diagnosis, people with type 1 diabetes have reduced β-cell function compared with healthy controls.

    “At diagnosis, people with type 1 diabetes have reduced β-cell function compared with healthy controls.61”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [61] Greenbaum, 2009, Preservation of β-cell function in autoantibody-positive youth with diabetes, Diabetes Care source

      The Results (page unavailable) show that among autoantibody-positive youth studied within one year of diagnosis, 31.2% had fasting C-peptide at or above the healthy-adolescent 5th percentile, supporting generally lower β-cell function relative to that reference population. The study does not measure function precisely at diagnosis, and its findings in youth do not establish the claim for all people with type 1 diabetes. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    Metformin has not been shown effective in people younger than 18 years who are overweight or obese and have type 1 diabetes.

    “it has not been shown to be effective in people younger than 18 years who are overweight or obese and have type 1 diabetes.86”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [86] Libman, 2015, Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: a randomized clinical trial, JAMA source

      The Abstract reports that adding metformin to insulin did not improve glycemic control after six months in overweight adolescents with type 1 diabetes. But the unqualified claim that it has not been shown effective overlooks favorable results for insulin dose and measures of adiposity. The trial also included participants up to age 19.6, rather than exclusively people younger than 18. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Metformin is the most commonly prescribed drug for type 1 diabetes patients with insulin resistance.

    “Metformin, an insulin sensitiser, is the most commonly prescribed drug for people with type 1 diabetes who have insulin resistance”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [86] Libman, 2015, Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: a randomized clinical trial, JAMA source

      The Introduction (page not provided) describes metformin’s glucose-lowering mechanisms, and the Abstract describes a trial of metformin added to insulin in overweight adolescents with type 1 diabetes. But our copy says metformin is commonly used for type 2 diabetes; it does not establish that metformin is the most commonly prescribed drug for people with type 1 diabetes and insulin resistance. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    The Diabetes Control and Complications Trial and the follow-up Epidemiology of Diabetes Interventions and Complications trial convincingly showed that achieving and maintaining glucose concentrations as close to those seen in people without diabetes as possible leads to a reduction in microvascular and cardiovascular type 1 diabetes complications.

    “This trial and the follow-up observational Epidemiology of Diabetes Interventions and Complications trial convincingly showed that achieving and maintaining glucose concentrations as close to those seen in people without diabetes as possible leads to a reduction in microvascular and cardiovascular type 1 diabetes complications.82”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [81] 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
    • cites [82] Nathan, 2014, The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview, Diabetes Care source
  • Classified as probably not a substantial claim. 13
  • May combine two claims. 18

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

    Premisecitation

    The rate of severe hypoglycaemia needing help from another person is 16-20 per 100 person-years.

    “Severe hypoglycaemic events requiring treatment assistance from another person occur at rates of 16–20 per 100 person-years;”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [103] Cengiz, 2013, Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D exchange clinic registry, Pediatr Diabetes source

      The Results (Severe Hypoglycemia; page unavailable) report that 6.2% of participants had at least one event in 12 months, not a rate of 16–20 events per 100 person-years. The Discussion explicitly says the study counted events involving seizure or loss of consciousness, rather than events merely requiring another person's assistance, and did not report an event rate. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [104] O'Connell, 2011, Reducing rates of severe hypoglycemia in a population-based cohort of children and adolescents with type 1 diabetes over the decade 2000–2009, Diabetes Care source

      The Abstract Results report a peak of 17.3 severe hypoglycemia events per 100 patient-years in 2001, within the claimed range, but a decline to 5.8 by 2006; they do not support 16–20 as a general rate. The Research Design and Methods section defines an event as one causing loss of consciousness or seizure, not one requiring assistance from another person. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [105] Karges, 2015, Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31,330 young patients with type 1 diabetes, Eur J Endocrinol source

  • May combine two claims.

    Premisecitation

    Type 1 diabetes can occur at any age, with up to 50% of cases occurring in adulthood.

    “the disease can occur at any age, with up to 50% of cases occurring in adulthood.7”
    • Also stated in: § Diagnosis · plain
      “Although traditional definitions classified type 1 diabetes as juvenile onset, the disease can occur at any age, with up to 50% of cases occurring in adulthood.7”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] 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

  • May combine two claims.

    Premisecitation

    Insulitis is common and intense in animal models of type 1 diabetes, but it is much rarer and more variable in human beings.

    “Although insulitis is common and intense in animal models of type 1 diabetes, it is much rarer and more variable in human beings (figure 3).60”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [60] Campbell-Thompson, 2015, Organ donor specimens: what can they tell us about type 1 diabetes?, Pediatr Diabetes source

      The section “Insulitis in the natural history of T1D” (page not provided) reports low proportions of affected islets in human donors and describes variation within and between donors. It does not establish that insulitis is common and intense in animal models, so the comparison is only partly supported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Globally, type 1 diabetes is increasing in incidence and prevalence, with overall annual increases in incidence of about 2-3% per year.

    “Globally, type 1 diabetes is increasing both in incidence and prevalence, with overall annual increases in incidence of about 2–3% per year.29,30”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [29] Maahs, 2010, Epidemiology of type 1 diabetes, Endocrinol Metab Clin North Am source

      The Incidence: Temporal Trends section reports a 2.8% average annual increase in type 1 diabetes incidence across studied populations in 57 countries, supporting the approximate 2–3% figure. That estimate concerns children aged 14 or younger, and the cited passages do not establish a global increase in prevalence. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [30] Mayer-Davis, 2017, Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012, N Engl J Med source

      The Introduction reports that type 1 diabetes incidence has increased worldwide, and the Discussion notes increased prevalence among U.S. youths. The Results report a 1.8% adjusted annual increase in incidence among U.S. youths, not a global increase of 2–3% per year; the paper does not establish a global prevalence trend. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Children with type 1 diabetes commonly present with polyuria, polydipsia, and weight loss; approximately one third present with diabetic ketoacidosis.

    “Children with type 1 diabetes commonly present with symptoms of polyuria, polydipsia, and weight loss; approximately a third present with diabetic ketoacidosis.6”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Dabelea, 2014, Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study, Pediatrics source

      The Abstract and Discussion (page unavailable in our copy) report that almost one-third of youth with type 1 diabetes present with DKA. The paper refers generally to signs and symptoms of diabetes, but does not identify polyuria, polydipsia, and weight loss as common presenting symptoms. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Survival and patient health have improved considerably, particularly in the past 25 years.

    “Although survival and patient health have improved considerably, particularly in the past 25 years, a cure for type 1 diabetes remains elusive.1,2”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [1] Barnett, 2018, Type 1 diabetes, Lancet source
    • cites [2] Skyler, 2018, Hope vs hype: where are we in type 1 diabetes?, Diabetologia source

      The Pancreas transplantation section (page unavailable) reports better 10-year survival for patients receiving a combined pancreas–kidney transplant than for those receiving a kidney transplant alone, and describes improving transplant outcomes. It does not establish that survival and health improved considerably for people with type 1 diabetes generally, particularly over the past 25 years. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Diabetic ketoacidosis accounts for 13-19% of type 1 diabetes-related mortality.

    “and accounts for 13–19% of type 1 diabetes-related mortality.105,110,111”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [110] Feltbower, 2008, Acute complications and drug misuse are important causes of death for children and young adults with type 1 diabetes: results from the Yorkshire Register of diabetes in children and young adults, Diabetes Care source

      The Results report 14 deaths from diabetic ketoacidosis, and Table 3 reports 108 deaths from all causes—about 13%. This supports the lower end of the cited range in this Yorkshire cohort, but the paper does not establish the 19% figure or the full range. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [111] Patterson, 2007, Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989, Diabetologia source

      The Results (page unavailable) report diabetic ketoacidosis mentioned in 27 of 141 deaths among people with type 1 diabetes, approximately 19%. But only 47 deaths were classified as directly attributable to diabetes; ketoacidosis was mentioned in 27 of those, approximately 57%. The paper therefore supports the 19% figure only for all deaths in the cohort, not a 13–19% range for deaths attributable to diabetes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Hypoglycaemic events are associated with 4-10% of type 1 diabetes-related deaths.

    “and are associated with 4–10% of type 1 diabetes-related deaths.110–112”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [110] Feltbower, 2008, Acute complications and drug misuse are important causes of death for children and young adults with type 1 diabetes: results from the Yorkshire Register of diabetes in children and young adults, Diabetes Care source
    • cites [111] Patterson, 2007, Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989, Diabetologia source

      The Results report five deaths directly ascribed to hypoglycaemia among 47 deaths assessed as directly attributable to diabetes—about 11% in this childhood-onset European cohort. The paper does not report a 4–10% range for diabetes-related deaths or establish that range beyond this cohort. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [112] Skrivarhaug, 2006, Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway, Diabetologia source

      The clinical-review results report 11 deaths classified as due to hypoglycaemia among 103 deaths—about 11%—in a Norwegian cohort with childhood-onset type 1 diabetes. This supports an association with deaths, but the paper does not establish the stated 4–10% range for type 1 diabetes-related deaths generally. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Three diabetes organizations advise an HbA1c goal below 53 mmol/mol (7.0%) for adults and below 58 mmol/mol (7.5%) for children with type 1 diabetes.

    “Guidelines from the American Diabetes Association, International Society for Pediatric and Adolescent Diabetes, and Candian Diabetes Association suggest a HbA1c target of less than 53 mmol/mol (7·0%) for adults and less than 58 mmol/mol (7·5%) in paediatric patients with type 1 diabetes;94–96”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [94] 2018, 6. Glycemic targets: standards of medical care in diabetes-2018, Diabetes Care

      Not checked in the free run.

    • cites [95] Rewers, 2014, ISPAD clinical practice concensus guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes, Pediatric Diabetes source
    • cites [96] 2013, Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Introduction, Can J Diabetes

      Not checked in the free run.

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

    Premisecitation

    Hypoglycaemic events leading to loss of consciousness or seizure occur at 2-8 per 100 person-years.

    “hypoglycaemic events leading to loss of consciousness or seizure occur at a rate of 2–8 per 100 person-years.103–105”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [103] Cengiz, 2013, Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D exchange clinic registry, Pediatr Diabetes source

      The Results (Severe Hypoglycemia; page unavailable) report that 6.2% of participants had at least one event involving seizure or loss of consciousness within 12 months. The Discussion explicitly distinguishes that percentage of participants from a rate measured as events per 100 person-years. The source therefore supports the event type and a broadly similar annual frequency, but not the claimed rate of 2–8 events per 100 person-years. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [104] O'Connell, 2011, Reducing rates of severe hypoglycemia in a population-based cohort of children and adolescents with type 1 diabetes over the decade 2000–2009, Diabetes Care source

      The Research Design and Methods section defines these events as hypoglycemia leading to loss of consciousness or seizure. The reported rate reached 5.8 per 100 patient-years, within the claimed range, but peaked at 17.3; the paper therefore does not support 2–8 as the range for its cohort of children with type 1 diabetes (Abstract, Results; page unavailable). (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [105] Karges, 2015, Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31,330 young patients with type 1 diabetes, Eur J Endocrinol source

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

    Premisecitation

    Cardiovascular disease is still the leading cause of early illness and death in type 1 diabetes; data indicate a life expectancy 8-13 years shorter than healthy people.

    “Cardiovascular disease remains the major cause of premature morbidity and mortality, with data119,120 suggesting an 8–13-year shorter life expectancy for people with type 1 diabetes than for healthy individuals.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [119] Huo, 2016, Burden of diabetes in Australia: life expectancy and disability-free life expectancy in adults with diabetes, Diabetologia source
    • cites [120] Livingstone, 2015, Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010, JAMA source

      The Results (Deaths by Cause; Examination of the Life Expectancy Differential by Age and Cause) identify ischemic heart disease as the most commonly reported cause of death and circulatory disease as the largest contributor to lost life expectancy. The Abstract (Results) reports losses of about 8 years in a preserved-kidney-function subgroup and 11–13 years overall. The paper does not establish cardiovascular disease as a leading cause of morbidity, and its comparator is the general population without type 1 diabetes, not specifically healthy individuals. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Over the last 25 years, people with type 1 diabetes have seen large drops in microvascular and macrovascular complication risks and better outcomes.

    “In the past 25 years, among people with type 1 diabetes the risks of microvascular and macrovascular compli-cations have substantially decreased and outcomes have improved.125,126”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [125] Lachin, 2014, Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study, Diabetes Care source

      The Introduction and Conclusions (page not specified) report substantial long-term benefits of intensive treatment for both microvascular disease and cardiovascular outcomes in the DCCT/EDIC participants with type 1 diabetes. They do not establish that complication risks declined over the past 25 years among people with type 1 diabetes generally; the comparison is intensive versus conventional treatment, not a population-wide trend over time. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [126] Fullerton, 2014, Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus, Cochrane Database Syst Rev source

      The review’s ‘Why it is important to do this review’ section says that treatment advances have made prospects for people with type 1 diabetes much better than in the past. Its Authors’ conclusions report reduced microvascular complications with tight glucose control, and ‘Agreements and disagreements with other studies or reviews’ reports a cardiovascular benefit in a follow-up study. It does not establish that both microvascular and macrovascular complication risks substantially declined across the type 1 diabetes population over the past 25 years; the latter section says its own meta-analysis cannot assess major macrovascular outcomes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Pancreas transplantation has been done for more than 50 years and is standard care for patients with end-stage renal failure who need a kidney transplant.

    “Pancreas transplants have been performed for over 50 years and have become a standard-of-care treatment in individuals who have developed end-stage renal failure and require kidney transplantation.158”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [158] Lindahl, 2013, Improved patient survival with simultaneous pancreas and kidney transplantation in recipients with diabetic end-stage renal disease, Diabetologia source

      The Introduction dates the first pancreas transplant to 1966, consistent with a history of more than 50 years by the time of the citing statement. It calls transplantation an effective option especially for patients with diabetes and end-stage renal disease, but does not establish it as standard care for everyone with end-stage renal failure who needs a kidney transplant; it describes eligibility limits and kidney-only alternatives. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Illness from immunosuppression and scarce donor islets limit how many patients can benefit from islet transplantation.

    “Moreover, morbidity associated with immunosuppression and limitations in the supply of donor islets restricts the number of people who can benefit from islet transplantation.161”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [161] Shapiro, 2006, International trial of the Edmonton protocol for islet transplantation, N Engl J Med source

  • May combine two claims.

    Premisecitation

    Autologous haemopoietic stem-cell transplantation and autologous T-regulatory cell administration are other novel approaches.

    “Other novel approaches include autologous haemopoietic stem-cell transplantation165,166 and autologous T-regulatory cell administration.167–169”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [165] Cantú-Rodríguez, 2016, Long-term insulin independence in type 1 diabetes mellitus using a simplified autologous stem cell transplant, J Clin Endocrinol Metab source
    • cites [166] Couri, 2009, C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus, JAMA source
    • cites [167] Bluestone, 2015, Type 1 diabetes immunotherapy using polyclonal regulatory T cells, Sci Transl Med source
    • cites [168] Marek-Trzonkowska, 2014, Therapy of type 1 diabetes with CD4(+)CD25(high)CD127-regulatory T cells prolongs survival of pancreatic islets—results of one year follow-up, Clin Immunol source
    • cites [169] Marek-Trzonkowska, 2012, Administration of CD4+CD25highCD127-regulatory T cells preserves β-cell function in type 1 diabetes in children, Diabetes Care source

  • May combine two claims.

    Premisecitation

    Type 1 diabetes is a heritable polygenic disease with identical twin concordance of 30-70%, sibling risk of 6-7%, and a risk of 1-9% for children who have a parent with diabetes.

    “Type 1 diabetes is a heritable polygenic disease with identical twin concordance of 30–70%,20 sibling risk of 6–7%, and a risk of 1–9% for children who have a parent with diabetes.21”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Redondo, 2008, Concordance for islet autoimmunity among monozygotic twins, N Engl J Med source
    • cites [21] Pociot, 2016, Genetic risk factors for type 1 diabetes, Lancet source

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

    Interpretationnone given

    Wide gaps remain in understanding type 1 diabetes and in standardising clinical care and reducing disease-associated complications and burden.

    “However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Knowledge about type 1 diabetes has grown rapidly in the past 25 years, producing broad understanding of its genetics, epidemiology, immune and β-cell phenotypes, and disease burden.

    “Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Two HLA class 2 haplotypes, DR3 and DR4-DQ8, are linked to approximately 50% of type 1 diabetes heritability and are prevalent in white people.

    “Two HLA class 2 haplotypes involved in anti gen presentation, HLA DRB1*0301-DQA1*0501-DQ*B10201 (DR3) and HLA DRB1*0401-DQA1*0301-DQB1*0301 (DR4-DQ8), are linked to approximately 50% of disease heritability and are prevalent in white people.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Noble, 2015, Immunogenetics of type 1 diabetes: a comprehensive review, J Autoimmun source

  • May combine two claims.

    Premisecitation

    HbA1c is less sensitive for diagnosing type 1 diabetes than fasting or stimulated blood glucose measurements because dysglycaemia progression can be rapid.

    “However, since dysglycaemia progression can be rapid in patients with type 1 diabetes, HbA1c is less sensitive for diagnosis than fasting or stimulated blood glucose measurements.5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] 2018, 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018, Diabetes Care

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased frequency of islet-specific autoreactive CD8+ T lymphocytes and decreased regulatory immune function have been associated with type 1 diabetes.

    “Increased frequency of islet-specific autoreactive CD8+ T lymphocytes and decreased regulatory immune function have been associated with type 1 diabetes.50”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Roep, 1990, T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins, Nature source

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

    Premisenone given

    Type 1 diabetes is now recognised to result from a complex interplay between environmental factors and microbiome, genome, metabolism, and immune systems that vary between individual cases.

    “What once seemed like a single autoimmune disorder, with roots in T-cell mediated attack of insulin-producing β cells, is now recognised to result from a complex interplay between environmental factors and microbiome, genome, metabolism, and immune systems that vary between individual cases.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Guidelines for diabetes care include periodic screening for autoimmune diseases, particularly thyroid and coeliac diseases.

    “Guidelines for the care of people with diabetes include periodic screening for these diseases, particularly thyroid and coeliac diseases.102”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] 2018, 3. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2018, Diabetes Care

      Not checked in the free run.

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

    Premisecitation

    In children with established type 1 diabetes, hospital care for diabetic ketoacidosis happens at 1-10 per 100 patient-years.

    “Treatment in hospital for diabetic ketoacidosis occurs at a rate of 1–10 per 100 patient-years in paediatric populations with established type 1 diabetes,”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Karges, 2015, Hospital admission for diabetic ketoacidosis or severe hypoglycemia in 31,330 young patients with type 1 diabetes, Eur J Endocrinol source

  • May combine two claims.

    Premisecitation

    Ciclosporin did not produce lasting remission, although insulin needs fell while patients were on it.

    “Although ciclosporin was unable to induce a durable disease remission, insulin requirements of patients decreased during active treatment, generating enthusiasm that immune modulation could treat type 1 diabetes.134–136”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [134] 1988, Cyclosporin-induced remission of IDDM after early intervention: association of 1 yr of cyclosporin treatment with enhanced insulin secretion, Diabetes source
    • cites [135] De Filippo, 1996, Long-term results of early cyclosporin therapy in juvenile IDDM, Diabetes source
    • cites [136] Feutren, 1986, Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial, Lancet source

  • May combine two claims.

    Premisecitation

    In type 1 diabetes, women have higher rates of premature death from any cause and vascular events than men.

    “women with type 1 diabetes have been shown to have higher rates of all-cause premature mortality and vascular events than do men with type 1 diabetes.128”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] Huxley, 2015, Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis, Lancet Diabetes Endocrinol source

  • May combine two claims.

    Premisecitation

    In experienced centres, combined kidney-pancreas transplant can give up to an 80% chance of insulin independence beyond 5 years, though it carries major surgical risk and needs immunosuppression.

    “Simultaneous kidney and pancreas transplantation in experienced centres can offer an up to 80% chance of insulin independence for over 5 years, but there is substantial surgical risk, and the requirement of immunosuppression.159”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Gruessner, 2013, The current state of pancreas transplantation, Nat Rev Endocrinol source

  • May combine two claims.

    Premisereasoning

    No drug has yet produced insulin independence or advanced to a positive phase 3 trial that changed clinical practice.

    “no drug has yet been able to induce insulin independence or progressed to a positive phase 3 trial that was translatable into clinical care.”
    Quote in the paperSubstantial claim
28 of 28

  • The paper relies on this without support.

    Most people diagnosed with type 1 diabetes do not have a relative with the disease or the highest risk combination of HLA alleles.

    “Despite known genetic underpinnings, most people who are diagnosed with type 1 diabetes do not have a relative with the disease or even the highest risk combination of HLA alleles, making attempts at primary disease prevention difficult.”

  • The paper relies on this without support.

    Glycaemic control for most people with type 1 diabetes is not optimised.

    “Additionally, despite advances in technology, glycaemic control for most people with type 1 diabetes is not optimised”

  • The paper relies on this without support.

    Many people with type 1 diabetes cannot access modern therapies because of the high costs of even basic care.

    “and many cannot access modern therapies because of the high costs of even basic care.”

  • The paper relies on this without support.

    Over time, many residual β cells are lost.

    “Over time, many of these residual cells are lost.”

  • The paper relies on this without support.

    Insulin remains the mainstay of therapy for type 1 diabetes.

    “Although insulin remains the mainstay of therapy, new insulin analogues with varying onsets and durations of action are widely available.”

  • The paper relies on this without support.

    Type 1 diabetes continues to impose substantial medical, psychological, and financial burden.

    “the disease continues to be associated with substantial medical, psychological, and financial burden.”

  • The paper relies on this without support.

    Hyperglycaemia is the primary risk factor for microvascular disease.

    “Hyperglycaemia is the primary risk factor for microvascular disease”

  • The paper relies on this without support.

    Reducing HbA1c through intensive diabetes management, particularly early in disease, is associated with about 70% reductions in incidence and slower progression of microvascular disease.

    “reducing HbA1c through intensive diabetes management, particularly early during disease, is associated with striking (about 70%) reductions in incidence and slower progression of microvascular disease.”

  • The paper relies on this without support.

    Differences in HbA1c do not fully explain variation in incidence and severity of complications between individuals.

    “However, differences in HbA1c do not fully explain the variation in the incidence of complications and the severity of disease between individuals.”

  • The paper relies on this without support.

    The risk of cardiovascular complications does not appear to be as attenuated by intensive blood sugar control as microvascular complications.

    “By contrast with microvascular complications, the risk of cardiovascular complications does not appear to be as attenuated by intensive blood sugar control.”

  • The paper relies on this without support.

    For over 30 years, most efforts to cure type 1 diabetes have focused on altering the immune system's attack on β cells.

    “For over 30 years, most efforts to cure type 1 diabetes have focused on altering the immune system’s attack on β cells.”

  • The paper relies on this without support.

    Islet transplantation is a low-risk procedure.

    “Islet transplantation is a low-risk procedure, with donor islets infused into the liver via the portal vein.”

  • The paper relies on this without support.

    Only a minority of islet transplant recipients achieve durable insulin independence.

    “However, only a minority of islet transplant recipients achieve durable insulin independence.”

  • The paper relies on this without support.

    Currently, islet transplantation is used in a small subset of patients with extremely severe hypoglycaemic unawareness.

    “Currently, islet transplantation is used in a small subset of patients who have extremely severe hypoglycaemic unawareness.”
14 of 14

Cites

Flagged first, then by citations

2 of the 179 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Eisenbarth, 1984, Autoimmune beta cell insufficiency—diabetes mellitus type 1, Triangle, 23, 111
  2. Thomas, 2016, Classifying diabetes by type 1 genetic risk shows autoimmune diabetes cases are evenly distributed above and below 30 years of age, Diabetologia, 59, S135

Cited by

Sorted by citations

Related

Authors
DiMeglio, L. A., Evans-Molina, C., & Oram, R. A.
Affiliations
  • Indiana University School of Medicine (US)
  • University of Exeter (GB)
Corresponding author
DiMeglio, Linda A
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2018-06
Volume
391
Issue
10138
Pages
2449-2462
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(18)31320-5
PMC
PMC6661119
OpenAlex
W2807893746
Cited by
1,561
References
179
Citations by year
2026: 125 · 2025: 246 · 2024: 261 · 2023: 305 · 2022: 276 · 2021: 174 · 2020: 97 · 2019: 60 · 2018: 12 · 2017: 1
FWCI
11.89
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01-BX001733)
  • Medical Research Council (MC_PC_15047)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK093954)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 1 diabetes, autoimmune disease, insulin deficiency, hyperglycemia, beta-cell preservation, disease burden, disease complications, clinical management, immunophenotype
MeSH terms
B-Lymphocytes, Blood Glucose, Diabetes Mellitus, Type 1, Haplotypes, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Phenotype, Blood Glucose Self-Monitoring

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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