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Cited by 270Diabetes Management and ResearchDiabetes Treatment and ManagementPancreatic function and diabetes

100 years of insulin: celebrating the past, present and future of diabetes therapy

Open access
Sims, Emily K., Carr, Alice L. J., Oram, Richard A., DiMeglio, Linda A., Evans-Molina, Carmella·2021·Nature Medicine
DOI 10.1038/s41591-021-01418-2PMC PMC8802620
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Abstract

The year 2021 marks the centennial of Banting and Best’s landmark description of the discovery of insulin. This discovery and insulin’s rapid clinical deployment effectively transformed type 1 diabetes from a fatal diagnosis into a medically manageable chronic condition. In this Review, we describe key accomplishments leading to and building on this momentous occasion in medical history, including advancements in our understanding of the role of insulin in diabetes pathophysiology, the molecular characterization of insulin and the clinical use of insulin. Achievements are also viewed through the lens of patients impacted by insulin therapy and the evolution of insulin pharmacokinetics and delivery over the past 100 years. Finally, we reflect on the future of insulin therapy and diabetes treatment, as well as challenges to be addressed moving forward, so that the full potential of this transformative discovery may be realized. Decades of scientific accomplishment have transformed diabetes treatment; this Review describes key milestones in our understanding of the insulin molecule and looks to the future of insulin therapy.

AI snapshot

Written from the paper’s full text.

TL;DR

This centennial review traces 100 years of insulin from Banting and Best’s discovery through molecular characterization, clinical insulin development, and evolving diabetes pathophysiology, and outlines future therapies. It emphasizes that insulin transformed type 1 diabetes into a manageable chronic condition while access and affordability remain major challenges.

Key findings

  • The Toronto group isolated insulin in 9 months, kept the longest-living pancreatectomized dog Marjorie alive for more than 70 days, and treated 14-year-old Leonard Thompson in January 1922; the team sold the patents to the University of Toronto for CAN$1, and Banting and Macleod received the 1923 Nobel Prize.
  • Islet autoantibody risk data show a single autoantibody confers 13% risk of type 1 diabetes over 15 years, whereas two or more autoantibodies confer 70% risk over 10 years and 84% over 15 years; type 2 diabetes now has more than 250 associated loci with 400 independent signals, explaining just under 20% of heritability.
  • Insulin therapy advanced from U-5 regular insulin to U-100 and concentrated preparations, from protamine zinc insulin in the 1930s to recombinant human insulin in 1978 and Humulin in 1983, and to rapid-acting lispro (1996), aspart (2000), and glulisine (2004), plus basal glargine (2000), detemir (2005), and degludec with >42 h action.
  • A 14-day course of teplizumab delayed stage 3 type 1 diabetes by a median of 32.5 months in high-risk multiple-autoantibody-positive individuals with dysglycemia; in the USA, diabetes costs averaged nearly US$800 per month, with nearly 50% from pharmacy costs, and insulin list prices rose 14–17% per year from 2012 to 2016.

Methods

  • Narrative review synthesizing historical, molecular, pathophysiologic, and clinical literature on insulin and diabetes over 100 years.
  • No primary data collection, systematic search strategy, or formal inclusion criteria are described.
  • The paper includes timelines, figures, and patient perspectives but does not report a meta-analysis or structured evidence synthesis.

Limitations

  • The paper states no formal limitations.
  • As a narrative review, it lacks a systematic search and inclusion criteria and presents no new primary data (evident from the text).
  • Potential selection or interpretation bias in the historical and clinical synthesis is not addressed (evident from the text); access and affordability are discussed as ongoing challenges, not as review limitations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41591-021-01418-2

Cites

152 of 152 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

50 of 121 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    In the 1950s, bioassays demonstrated that human plasma from young, ketotic patients with diabetes was unable to lower blood glucose values when injected into diabetic rats, compared to plasma from older obese females with nonketotic hyperglycemia.

    “Initial work used bioassays demonstrating that compared to human plasma from older obese females with nonketotic hyperglycemia, human plasma from young, ketotic patients with diabetes was unable to lower blood glucose values when injected into diabetic rats24.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Bornstein, J. & Lawrence, R. Two types of diabetes mellitus, with and without available plasma insulin. Br. Med. J. 1, 732 (1951). source
  • Interpretationcitation

    By the end of the 1970s, work led to recognition that immune-mediated loss of insulin-secreting cells was the cause of insulin-dependent diabetes.

    “By the end of the 1970s, this work led to the recognition that immune-mediated loss of insulin-secreting cells was the cause of insulin-dependent diabetes3.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Gale, E. A. The discovery of type 1 diabetes. Diabetes 50, 217–226 (2001). source

      In “The Road to Autoimmune Diabetes” (page unavailable), Gale describes evidence that converged on an autoimmune paradigm during the 1970s, and “Animal Models of Diabetes” describes immune-mediated models developed in 1976. But the latter section also says viral infection was still thought to account for many cases and describes both immune-mediated and non-immune-mediated forms of type 1 diabetes. The claim overstates the paper by presenting immune-mediated cell loss as the established cause of all insulin-dependent diabetes by the end of the decade. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    Physiologic studies using intravenous and oral glucose tolerance tests and hyperglycemic clamps have demonstrated a feedback loop in which decreased insulin sensitivity is tightly associated with increased insulin secretion from the beta cell, termed the disposition index.

    “These studies have demonstrated that to maintain glucose homeostasis, a feedback loop exists in which decreased insulin sensitivity is tightly associated with increased insulin secretion from the beta cell, with this hyperbolic relationship between beta cell responsivity and insulin sensitivity termed the disposition index67,68.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [67] Kahn, S. E. et al. Quantification of the relationship between insulin sensitivity and β-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42, 1663–1672 (1993). source
    • cites [68] Bergman, R. N., Phillips, L. S. & Cobelli, C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J. Clin. Invest. 68, 1456–1467 (1981). source

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

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  • Premisecitation

    Genome-wide linkage and association studies have described more than 60 loci outside the HLA region that contribute to type 1 diabetes genetic risk.

    “Subsequent genome-wide linkage and then genome-wide association studies of cases and controls have described more than 60 loci outside the HLA region that also contribute to type 1 diabetes genetic risk53.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [53] Buniello, A. et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics. Nucleic Acids Res. 47, D1005–D1012 (2019). source

      The Introduction discusses GWAS identifying regions associated with common traits, but does not make a type 1 diabetes finding. Searches for type 1 diabetes, more than 60 loci, non-HLA risk, and linkage studies found no passage in our copy addressing the claim. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • Premisecitation

    Over 40% of genes associated with type 1 diabetes are expressed in the islet or beta cell.

    “More recently, there has been increased focus on whether many of these variants may influence beta cell interactions with the immune system, with over 40% of genes associated with type 1 diabetes being expressed in the islet or beta cell.”
    Quote in the paperNot a substantial claim5 of 6 sources checked
    • cites [54] Coomans de Brachène, A. et al. IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells. Diabetologia 61, 636–640 (2018). source

      The Introduction identifies TYK2 as a type 1 diabetes candidate gene involved in human beta cells, but it gives no proportion of associated genes expressed in islets or beta cells. Searches for the 40% figure and for expression of type 1 diabetes–associated genes found no passage supporting the claimed proportion. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [55] Marroqui, L. et al. Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes. Diabetologia 60, 656–667 (2017). source

      The Discussion (page unavailable) describes type 1 diabetes candidate genes expressed in human pancreatic islets, supporting the qualitative point. It gives no proportion of all associated genes expressed in islets or beta cells, so it does not support the “over 40%” figure. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [56] Fløyel, T. et al. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients. Proc. Natl Acad. Sci. USA 111, 10305–10310 (2014). source
    • cites [57] Eizirik, D. L. et al. The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet. 8, e1002552 (2012). source
    • cites [58] Eizirik, D. L., Colli, M. L. & Ortis, F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat. Rev. Endocrinol. 5, 219–226 (2009). source
    • cites [59] Lee, H. et al. Beta cell dedifferentiation induced by IRE1α deletion prevents type 1 diabetes. Cell Metab. 31, 822–836 (2020). source

      The Introduction says genetic predisposition is associated with type 1 diabetes, and the Results report gene-expression changes in islets from IRE1α-deficient mice. Neither passage gives the proportion of type 1 diabetes-associated genes expressed in islets or beta cells; searches for that proportion and for “40%” found no supporting passage in our copy. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Premisecitation

    In progression to type 2 diabetes, beta cell function is initially increased, maintaining glucose levels at higher but still normal levels; around 3 years before onset, decreasing insulin secretion and an accelerated rise in blood glucose levels are observed.

    “Initially, beta cell function is increased, maintaining glucose levels at higher but still normal levels and below the diagnostic threshold for diabetes. However, the ability of the beta cell to maintain this response is finite in some individuals. As the beta cells undergo a process of failure that has been linked with a number of molecular processes, including oxidative and endoplasmic reticulum”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [72] Lillioja, S. et al. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N. Engl. J. Med. 318, 1217–1225 (1988). source
    • cites [73] Martin, B. C. et al. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 340, 925–929 (1992). source
    • cites [74] Saad, M. F. et al. Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes. Lancet 1, 1356–1359 (1989). source
    • cites [75] Tabak, A. G. et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373, 2215–2221 (2009). source

  • May combine two claims.

    Premisecitation

    Once insulin therapy was available, clinicians related differences to insulin requirements, with insulin-insensitive patients usually presenting later in life, with obesity and a more insidious presentation.

    “Once insulin therapy was available, clinicians related these differences to insulin requirements, with insulin-insensitive patients usually presenting with symptoms later in life, in association with obesity and a more insidious presentation20,21.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [20] Pincus, G., Joslin, E. & White, P. The age-incidence relations in diabetes mellitus. Am. J. Med. Sci. 188, 116–121 (1934). source
    • cites [21] MacLean, H. Some observations on diabetes and insulin in general practice. Postgrad. Med. J. 1, 73–77 (1926). source

      In 'DIETETIC OR INSULIN TREATMENT ?' (page unavailable), MacLean contrasts young patients with true diabetes, for whom insulin is usually necessary, with patients who are 'usually too fat.' The 'INSULIN TREATMENT' section says insulin is usually unnecessary for hepatic glycosuria in middle or old age. But the paper does not describe these patients as insulin-insensitive or say their symptoms present insidiously; it explicitly distinguishes hepatic glycosuria from true diabetes. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Despite the large number of associated loci, their individual contributions to overall risk are moderate, explaining just under 20% of heritability and highlighting missing heritability.

    “Despite the large number of associated loci, their individual contributions to overall risk are moderate, explaining just under 20% of heritability and highlighting the proportion of ‘missing heritability’ that is still to be fully elucidated.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [79] Mahajan, A. et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat. Genet. 50, 1505–1513 (2018). source

      The Results section ('The contribution of lower-frequency variants'; page unavailable) says most associated variants have modest effects and reports that common and lower-frequency signals explain 16.3% and 1.13% of T2D phenotypic variance, respectively. The separate 'Heritability estimates' section estimates chip heritability at 18%, about half the estimate from family studies. The claim conflates variance explained by associated signals with the proportion of heritability they explain; the paper does not say those loci explain just under 20% of heritability. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a seminal analysis of four birth cohorts, presence of a single islet autoantibody is associated with a 13% risk of developing type 1 diabetes over 15 years; two or more antibodies are associated with a 70% risk over 10 years and an 84% risk over 15 years.

    “A seminal analysis of four different birth cohorts from the USA, Finland and Germany demonstrated that the presence of a single islet autoantibody is associated with a 13% risk of developing type 1 diabetes over 15 years. In contrast, having two or more antibodies is associated with a 70% risk over 10 years of observation and an 84% risk over 15 years63.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [63] Ziegler, A. G. et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. J. Am. Med. Assoc. 309, 2473–2479 (2013). source

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

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  • May combine two claims.

    Premisecitation

    Contemporary and large natural history studies have shown that type 1 diabetes is a heterogeneous disorder and that features beyond autoimmunity, including metabolic factors, exocrine function and environmental exposures, impact progression to clinical disease.

    “Contemporary and large natural history studies assembled based on HLA genotypes and family history have shown that type 1 diabetes is a heterogenous disorder and that features beyond autoimmunity, including metabolic factors, exocrine function and environmental exposures, impact progression to clinical disease61.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [61] Battaglia, M. et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care 43, 5–12 (2020). source

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

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  • May combine two claims.

    Premisecitation

    Frederick Sanger determined the amino acid sequences of the A and B chains of insulin; by 1955 he demonstrated the position of the two disulfide bonds linking the A and B chains and the intrachain disulfide bond within the A chain.

    “In the early 1950s, Frederick Sanger determined the amino acid sequences of the A and B chains of insulin87–90. By 1955, he would demonstrate the position of the two disulfide bonds linking the A and B chains and the intrachain disulfide bond within the A chain, and in 1958, he was awarded the Nobel Prize in Chemistry91–93.”
    Quote in the paperNot a substantial claim6 of 7 sources checked
    • cites [87] Sanger, F. & Tuppy, H. The amino-acid sequence in the phenylalanyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates. Biochem. J. 49, 463–481 (1951). source

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

      Experimental — accuracy not yet measured
    • cites [88] Sanger, F. & Tuppy, H. The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates. Biochem. J. 49, 481–490 (1951). source

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

      Experimental — accuracy not yet measured
    • cites [89] Sanger, F. & Thompson, E. The amino-acid sequence in the glycyl chain of insulin. 1. The identification of lower peptides from partial hydrolysates. Biochem. J. 53, 353–366 (1953). source

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

      Experimental — accuracy not yet measured
    • cites [90] Sanger, F. & Thompson, E. The amino-acid sequence in the glycyl chain of insulin. 2. The investigation of peptides from enzymic hydrolysates. Biochem. J. 53, 366–374 (1953). source

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

      Experimental — accuracy not yet measured
    • cites [91] Berg, P. Fred Sanger: a memorial tribute. Proc. Natl Acad. Sci. USA 111, 883–884 (2014). source
    • cites [92] Ryle, A. P., Sanger, F., Smith, L. F. & Kitai, R. The disulphide bonds of insulin. Biochem. J. 60, 541–556 (1955). source
    • cites [93] Sanger, F. Chemistry of insulin; determination of the structure of insulin opens the way to greater understanding of life processes. Science 129, 1340–1344 (1959). source

  • May combine two claims.

    Premisecitation

    Franco Bottazzo was the first to successfully visualize islet cell antibodies using indirect immunofluorescence, confirming the presence of antibodies reactive to the islet.

    “In a now famous ‘eureka’ moment, in 1974, Franco Bottazzo, a research fellow in Deborah Doniach’s laboratory in London, was the first to successfully visualize islet cell antibodies using indirect immunofluorescence, thereby confirming the presence of antibodies reactive to the islet.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Gale, E. A. The discovery of type 1 diabetes. Diabetes 50, 217–226 (2001). source
    • cites [5] Bottazzo, G., Florin-Christensen, A. & Doniach, D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 304, 1279–1283 (1974). source

  • May combine two claims.

    Premisecitation

    Inhaled insulin has a faster onset of action and offset of effect than any of the injected insulins.

    “Advances in insulin delivery have also included the development of inhaled insulin with a faster onset of action and offset of effect than any of the injected insulins121.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [121] Oleck, J., Kassam, S. & Goldman, J. D. Commentary: why was inhaled insulin a failure in the market? Diabetes Spectr. 29, 180–184 (2016). source

      The opening section calls Exubera and Afrezza rapid-acting inhaled insulins, and “Emerging Safety Concerns” describes Afrezza’s rapid offset (page unavailable in our copy). The paper does not establish that inhaled insulin has a faster onset and offset than every injected insulin. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Heterozygous mutations can impair normal folding of insulin precursors, yielding abnormal molecules that act in a dominant-negative fashion to impair the exit of all proinsulin from the endoplasmic reticulum; this initially causes insulin deficiency, followed by severe beta cell endoplasmic reticulum stress and apoptosis.

    “Heterozygous mutations can also impair the normal folding of insulin precursors, yielding abnormal molecules that act in a dominant-negative fashion to impair the exit of all proinsulin from the endoplasmic reticulum100. This initially causes insulin deficiency, followed by severe beta cell endoplasmic reticulum stress and apoptosis100,101.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [100] Stoy, J. et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc. Natl Acad. Sci. USA 104, 15040–15044 (2007). source
    • cites [101] Liu, M. et al. Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant diabetes. Diabetes 61, 828–837 (2012). source

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

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  • May combine two claims.

    Premisecitation

    Smart insulin pens allow for tracking of insulin dosing and integration with smartphone applications to provide reminders, integrate with blood glucose data and provide dosing recommendations.

    “More recently developed ‘smart’ insulin pens allow for tracking of insulin dosing, and integration with smartphone applications to provide reminders, integrate with blood glucose data and provide dosing recommendations120.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [120] Kesavadev, J., Saboo, B., Krishna, M. B. & Krishnan, G. Evolution of insulin delivery devices: from syringes, pens, and pumps to DIY artificial pancreas. Diabetes Ther. 11, 1251–1269 (2020). source

      The Insulin Pen sections on Next-Generation and Connected Pens (page unavailable) describe dose tracking, smartphone connectivity, sharing data with glucose-monitoring devices, and a bolus advisor for dosing guidance. They do not describe smartphone reminders, so that part of the claim is unsupported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The first long-acting insulin was developed in the 1930s by H. C. Hagedorn; it was a suspension protamine zinc insulin based on the discovery that insulin action could be prolonged by adding protamine obtained from river trout semen, and its action lasted 24-36 h.

    “Towards a goal of reducing the need for multiple daily injections, the first long-acting insulin was developed in the 1930s by H. C. Hagedorn. It was a suspension protamine zinc insulin that was based on the discovery that insulin action could be prolonged by adding protamine obtained from river trout semen106. The action of protamine zinc insulin lasted 24–36 h.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [106] Hirsch, I. B., Juneja, R., Beals, J. M., Antalis, C. J. & Wright, E. E. The evolution of insulin and how it informs therapy and treatment choices. Endocr. Rev. 41, 733–755 (2020). source

      The Basal Insulin > Intermediate-acting insulin section (page unavailable) says that Hagedorn and Jensen found in 1936 that protamine from trout semen prolonged insulin’s effects, and it lists protamine zinc insulin among later longer-acting formulations. It does not identify Hagedorn’s formulation as the first long-acting insulin or give protamine zinc insulin a 24–36-hour duration; it also does not specify river trout. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The first long-acting once-daily basal insulin, glargine, was approved in 2000; it was designed to have an extended duration of action through amino acid modifications in both chains.

    “The first long-acting once-daily basal insulin, glargine, was approved in 2000 (ref. 117). It was designed to have an extended duration of action through amino acid modifications in both chains (A chain A21 asparagine substituted by glycine and B chain elongated by adding two arginines).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [117] Pieber, T. R., Eugene-Jolchine, I. & Derobert, E. Efficacy and safety of HOE 901 versus NPH insulin in patients with type 1 diabetes. The European Study Group of HOE 901 in type 1 diabetes. Diabetes Care 23, 157–162 (2000). source

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

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  • May combine two claims.

    Premisecitation

    The development of reliable and accurate continuous glucose monitors allowed for the possibility of integration of glucose data with pump insulin delivery and sparked interest to develop safe and effective algorithms for closed-loop systems.

    “The development of reliable and accurate continuous glucose monitors allowed for the possibility of integration of glucose data with pump insulin delivery and sparked a flurry of interest to develop safe and effective algorithms for closed-loop systems, notably championed by do-it-yourself movements from the diabetes community itself122,125.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [122] Kovatchev, B. A century of diabetes technology: signals, models, and artificial pancreas control. Trends Endocrinol. Metab. 30, 432–444 (2019). source
    • cites [125] Kesavadev, J., Srinivasan, S., Saboo, B., Krishna, B. M. & Krishnan, G. The do-it-yourself artificial pancreas: a comprehensive review. Diabetes Ther. 11, 1217–1235 (2020). source

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

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

    Premisecitation

    In a recent analysis of children and adults with type 1 diabetes in the USA, the average cost associated with diabetes totaled nearly US$800 per month, with nearly 50% driven by pharmacy costs.

    “In a recent analysis of children and adults with type 1 diabetes in the USA, the average cost associated with diabetes totaled nearly US$800 per month, with nearly 50% driven by pharmacy costs141.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [141] Simeone, J. C. et al. Healthcare resource utilization and cost among patients with type 1 diabetes in the United States. J. Manag. Care Spec. Pharm. 26, 1399–1410 (2020). source

      The Conclusions report nearly $800 in diabetes-related costs per patient per month for pediatric and adult patients with type 1 diabetes in the United States. However, the HCRU and Cost During Follow-up section puts pharmacy costs at 55.3%–61.1% of diabetes-related costs—over half, rather than nearly 50%. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    In 1985 the first insulin pen was launched by Novo Nordisk.

    “In 1985 the first insulin pen was launched by Novo Nordisk120.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [120] Kesavadev, J., Saboo, B., Krishna, M. B. & Krishnan, G. Evolution of insulin delivery devices: from syringes, pens, and pumps to DIY artificial pancreas. Diabetes Ther. 11, 1251–1269 (2020). source

  • May combine two claims.

    Premisecitation

    Early twin studies indicated >90% concordance of diabetes in those diagnosed at older ages (type 2 diabetes) and approximately 50% concordance of diabetes occurring in children and young adults (type 1 diabetes).

    “A theme of early twin studies indicated >90% concordance of diabetes in those diagnosed at older ages (that is, type 2 diabetes) and approximately 50% concordance of diabetes occurring in children and young adults (that is, type 1 diabetes)8,46,47.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Cudworth, A. G. & Woodrow, J. C. HL-A antigens and diabetes mellitus. Lancet 2, 1153 (1974). source
    • cites [46] Gottlieb, M. S. & Root, H. F. Diabetes mellitus in twins. Diabetes 17, 693–704 (1968). source
    • cites [47] Tattersall, R. B. & Pyke, D. A. Diabetes in identical twins. Lancet 2, 1120–1125 (1972). source

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

    Premisenone given

    The first documented patient to receive insulin was 14-year-old Leonard Thompson, who received his first injection in January 1922.

    “The first documented patient to receive insulin was 14-year-old Leonard Thompson. He received his first injection in January 1922, at a time when he, by all accounts, was near death.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    A small number of HLA class 2 alleles explain a large proportion of disease heritability in many autoimmune diseases including type 1 diabetes.

    “To this day, a standout feature of many autoimmune diseases including type 1 diabetes is that a small number of HLA class 2 alleles, critical for antigen presentation by the immune system, explain a large proportion of disease heritability.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Singal, D. P. & Blajchman, M. A. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes 22, 429–432 (1973). source

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

    Interpretationnone given

    Insulin has served as the centerpiece for advances in crystallography, molecular biology, prohormone processing, autoimmunity, physiology, and precision health and genetics, and formed the basis for four Nobel Prizes.

    “Beyond its immediate therapeutic impact, insulin has served as the centerpiece for incredible advances in the fields of crystallography, molecular biology, prohormone processing, autoimmunity, physiology, and precision health and genetics, while forming the basis for four Nobel Prizes.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Banting and Macleod were awarded the 1923 Nobel Prize in Physiology or Medicine.

    “Ultimately Banting and Macleod were awarded the 1923 Nobel Prize in Physiology or Medicine, with Banting sharing his portion of the award with Best, and Macleod doing the same with Collip4,18.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Bliss, M. The history of insulin. Diabetes Care 16, 4–7 (1993). source
    • cites [18] Banting, F. G., Best, C. H., Collip, J. B., Campbell, W. R. & Fletcher, A. A. Pancreatic extracts in the treatment of diabetes mellitus. Can. Med. Assoc. J. 12, 141 (1922).

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

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

    Premisecitation

    In 1935, Dorothy Crowfoot Hodgkins took the first diffraction images of insulin crystals; she solved the crystal structure in 1969, showing insulin was a hexamer composed of three heterodimers.

    “In 1935, a research fellow, Dorothy Crowfoot Hodgkins, took the first diffraction images of insulin crystals84. She would continue her work on the insulin molecule on and off throughout her career, ultimately solving the crystal structure in 1969 and showing that insulin was a hexamer composed of three heterodimers85.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [84] Crowfoot, D. X-ray single crystal photographs of insulin. Nature 135, 591–592 (1935). source
    • cites [85] Adams, M. J. et al. Structure of rhombohedral 2 zinc insulin crystals. Nature 224, 491–495 (1969). source

  • May combine two claims.

    Premisecitation

    The majority of type 2 diabetes-associated loci are linked to beta cells, supporting the idea that impaired beta cell function is critical to type 2 diabetes pathogenesis.

    “The majority of associated loci are linked to beta cells, supporting the idea that impaired beta cell function is critical to type 2 diabetes pathogenesis78,80.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [78] Grant, S. F. et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat. Genet. 38, 320–323 (2006). source
    • cites [80] McCarthy, M. I. Genomics, type 2 diabetes, and obesity. N. Engl. J. Med. 363, 2339–2350 (2010). source

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

    Interpretationnone given

    Type 1 diabetes seems to be a discrete entity defined by islet autoimmunity, beta cell destruction and a relatively small group of genes.

    “Whereas type 1 diabetes seems to be a discrete entity defined by islet autoimmunity, beta cell destruction and a relatively small group of genes, an outstanding question is whether type 2 diabetes will be resolved into multiple subtypes/clusters defined by genetic associations, mechanisms and phenotype81–83 and whether this approach will improve precision intervention and treatment.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The widely adopted 1986 Eisenbarth model suggested that type 1 diabetes was a chronic autoimmune disease, with genetically predisposed individuals encountering a hypothetical triggering event that activated islet autoimmunity, yielding progressive beta cell destruction and insulin deficiency.

    “The widely adopted 1986 Eisenbarth model suggested that type 1 diabetes was a chronic autoimmune disease, with genetically predisposed individuals encountering a hypothetical triggering event that activated islet autoimmunity, yielding progressive beta cell destruction and insulin deficiency45.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Eisenbarth, G. S. Type I diabetes mellitus. A chronic autoimmune disease. N. Engl. J. Med. 314, 1360–1368 (1986). source

  • May combine two claims.

    Premisecitation

    Pancreatic insulin was almost undetectable in young people with diabetes, in contrast to a nearly ~50% reduction in older people with diabetes relative to nondiabetic controls.

    “These experiments showed that pancreatic insulin was almost undetectable in young people with diabetes. This was in contrast to the nearly ~50% reduction observed in older people with diabetes relative to nondiabetic controls25.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Wrenshall, G. A., Bogoch, A. & Ritchie, R. Extractable insulin of pancreas: correlation with pathological and clinical findings in diabetic and nondiabetic cases. Diabetes 1, 87–107 (1952). source

  • May combine two claims.

    Premisecitation

    The Toronto group proved that pancreatic extract regulated blood glucose levels and urinary glucose excretion by reinjecting it into pancreatectomized dogs, keeping Marjorie alive for more than 70 days.

    “They would go on to prove that the pancreatic extract regulated blood glucose levels and urinary glucose excretion by reinjecting it into pancreatectomized dogs, while keeping the longest living of these dogs, Marjorie, alive for more than 70 days.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Bliss, M. The history of insulin. Diabetes Care 16, 4–7 (1993). source

  • May combine two claims.

    Interpretationcitation

    These findings suggested that differences in glucose gradients may be related to forearm muscle resistance to insulin action and that diabetes could be separated into distinct subgroups-insulin insufficiency and insulin insensitivity.

    “These findings suggested that differences in glucose gradients may be related to forearm muscle resistance to insulin action and that those with diabetes could be separated into distinct subgroups—the first with disease resulting from insulin insufficiency and the second with disease occurring due to insulin insensitivity23.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Himsworth, H. P. Diabetes mellitus: its differentiation into insulin-sensitive and insulin insensitive types. Lancet 227, 127–130 (1936). source

  • May combine two claims.

    Premisecitation

    In 1965, Willy Gepts analyzed a larger number of pancreatic samples from children who died near clinical diagnosis and showed islets with lymphocytic infiltrates in the majority of autopsy specimens, suggesting a link to an immunologic origin of disease.

    “However, in 1965, Willy Gepts analyzed a larger number of pancreatic samples obtained from children who died near the time of clinical diagnosis and showed islets with lymphocytic infiltrates in the majority of autopsy specimens, suggesting a clearer link to an immunologic origin of disease38.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Gepts, W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14, 619–633 (1965). source

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

    Premisecitation

    In 1979, the National Diabetes Data Group proposed classifying diabetes using the terms type 1 (insulin dependent), type 2 (noninsulin dependent), and 'other'.

    “Based on these findings, in 1979 the National Diabetes Data Group proposed classifying diabetes using the terms employed today: type 1 (insulin dependent), type 2 (noninsulin dependent), and ‘other’ denoting forms of disease not fitting into either of these two categories42.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28, 1039–1057 (1979). source

  • May combine two claims.

    Interpretationcitation

    There are continued challenges with accessibility and equity in diabetes care, which have been exacerbated by advances in diabetes care technology.

    “there are continued challenges with accessibility and equity, which have only been exacerbated by advances in diabetes care technology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The 1993 Diabetes Control and Complications Trial and 1998 United Kingdom Prospective Diabetes Study demonstrated definitive relationships between glycemic control and microvascular complications and showed that lower A1cs were associated with higher rates of severe hypoglycemia.

    “The 1993 publication of the Diabetes Control and Complications Trial112 and 1998 United Kingdom Prospective Diabetes Study113–115 demonstrated definitive relationships between glycemic control and microvascular complications and showed that lower A1cs were associated with higher rates of severe hypoglycemia.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [112] The Diabetes Control and Complications Trial (DCCT) Research Group. 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. 329, 977–986 (1993). source
    • cites [113] United Kingdom Prospective Diabetes Study (UKPDS). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352, 854–865 (1998). source
    • cites [114] United Kingdom Prospective Diabetes Study (UKPDS). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837–853 (1998). source
    • cites [115] United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. Br. Med. J. 310, 83–88 (1995). source

  • May combine two claims.

    Premisecitation

    After the first clinical use of regular insulin, the pancreatic extract was further purified, the source moved to pork and later beef pancreas, and the concentration was increased from U-5 to U-10, U-20, U-40 and U-80 preparations.

    “After the first clinical use of ‘regular’ insulin for patients, the pancreatic extract was further purified, the source of insulin moved to pork and later beef pancreas, and the concentration was increased from the original commercially available U-5 insulin (for example, 5 units ml−1) to U-10, U-20, U-40 and U-80 preparations105.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Ovalle, F. et al. Understanding concentrated insulins: a systematic review of randomized controlled trials. Curr. Med. Res. Opin. 34, 1029–1043 (2018). source

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

    Premisecitation

    In 1968, Ronald Chance published the porcine sequence of the proinsulin molecule.

    “In 1968, Ronald Chance at Lilly Research Laboratories in Indianapolis published the porcine sequence of the proinsulin molecule96.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Chance, R. E., Ellis, R. M. & Bromer, W. W. Porcine proinsulin: characterization and amino acid sequence. Science 161, 165–167 (1968). source

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

    Interpretationreasoning

    Improvements in insulin delivery and monitoring and alternative cell-based sources of insulin have the potential to broadly impact diabetes management and will benefit individuals with type 1 and type 2 diabetes, as well as rarer forms of the disease.

    “Improvements in insulin delivery and monitoring and alternative cell-based sources of insulin have the potential to broadly impact diabetes management and will benefit individuals with type 1 and type 2 diabetes, as well as rarer forms of the disease.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Subsequent discoveries since the discovery of insulin have improved life expectancy and quality of life for those with diabetes.

    “the subsequent discoveries that have improved life expectancy and quality of life for those with diabetes (Fig. 3)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Altered interaction of structurally abnormal insulin with the insulin receptor leads to altered insulin action, hyperinsulinemia and adult-onset diabetes with autosomal dominant inheritance.

    “Altered interaction of structurally abnormal insulin with the insulin receptor leads to altered insulin action, hyperinsulinemia and adult-onset diabetes with autosomal dominant inheritance98.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Shoelson, S. et al. Three mutant insulins in man. Nature 302, 540–543 (1983). source

  • Classified as probably not a substantial claim.

    Interpretationnone given

    In the 100 years since the discovery of insulin, there has been remarkable progress in the ability to treat type 1 and type 2 diabetes, facilitated by improved understanding of the pathophysiology of the disease and improvements in insulin formulation and delivery.

    “In the 100 years since the discovery of insulin, there has been remarkable progress in our ability to treat type 1 and type 2 diabetes, facilitated by an improved understanding of the pathophysiology of the disease and improvements in insulin formulation and delivery.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the 1920s, the Toronto team struggled at the outset to produce enough insulin to meet rapidly growing demand and to distribute insulin equitably.

    “In the 1920s, having developed a transformative and lifesaving therapy, the Toronto team faced an almost impossible challenge, and they struggled at the outset to produce enough insulin to meet a rapidly growing demand and to distribute insulin in a fashion that was equitable1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Bliss, M. The Discovery of Insulin (Univ. Chicago Press, 1982). source

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

    Premisenone given

    Insulin was the first protein successfully sequenced and the first molecule characterized as a prohormone.

    “In addition to being the first protein that was successfully sequenced, insulin was the first molecule to be characterized as a prohormone.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Detemir was approved in 2005; it has a fatty-acid side chain bound to position B29 that facilitates self-association and an affinity for albumin allowing for prolonged duration of action without peaks.

    “The next long-acting basal insulin, detemir, was approved in 2005 (ref. 118). Detemir has a fatty-acid (myristic acid) side chain bound to position B29 that facilities self-association and an affinity for albumin allowing for prolonged duration of action without peaks.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] US Food and Drug Administration. Levemir insulin detemir[rDNA origin] injection drug approval package. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021-536_LevemirTOC.cfm (2005).

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

  • May combine two claims.

    Premisecitation

    Before the 1980s, all insulin preparations were derived from animal sources; increased clinical demand and tedious extraction processes outstripped available supplies.

    “Before the 1980s, all insulin preparations were derived from animal sources. However, with increased clinical demand and tedious extraction processes (for example, more than 23,500 pancreata were needed to make 1 lb of insulin), available supplies were being outstripped108.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Fraser, L. Cloning insulin. Genentech https://www.gene.com/stories/cloning-insulin (7 April 2016).

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

41 of 41

  • The paper relies on this without support.

    The year 2021 marks the 100th anniversary of the discovery of insulin.

    “The year 2021 marks the centennial of Banting and Best’s landmark description of the discovery of insulin.”

  • The paper relies on this without support.

    Population-based screening for type 1 diabetes is increasingly performed in several countries and regions, based on autoantibody measurement and sometimes genetic risk assessment.

    “In this regard, population-based screening is now being increasingly performed in several countries and regions, and is based on autoantibody measurement and, in some cases, assessment of genetic risk.”

  • The paper relies on this without support.

    For type 1 diabetes, the goal of eliminating exogenous insulin therapy is a centerpiece of clinical trials testing disease-modifying interventions, including ongoing work in Type 1 Diabetes TrialNet, the Immune Tolerance Network and INNODIA.

    “For type 1 diabetes, this goal is a centerpiece of clinical trials testing disease-modifying interventions, including work that is ongoing in several large networks such as Type 1 Diabetes TrialNet, the Immune Tolerance Network and INNODIA.”
3 of 3

Cites

Flagged first, then by citations

1 of the 153 references couldn’t be matched to a known paper.

Research works printed but not linked: 11

  1. Dobson, M. Nature of the urine in diabetes. Med. Obs. Inq. 5, 298–310 (1776).
  2. De Meyer, J. Action de la sécrétion interne du pancréas sur différents organes et en particulier sur la sécrétion rénale. Arch. Fisiol. 7, 96–99 (1909).
  3. Lancereaux, E. Le diabète maigre, ses symptômes, son évolution, son pronostic et son traitement. Union Med. 29, 161 (1880).
  4. Renold, A. E., Soeldner, S. & Steinke, J. in Ciba Foundation Symposium ‐ Aetiology of Diabetes Mellitus and its Complications (Colloquia on Endocrinology) Vol. 15 (eds. M.P. Cameron, M. P. & O’Connor, M.) 122–139 (Wiley, 1964).
  5. Lavaux, J. P., Ooms, H. A. & Christiansen, A. H. Insulin antibodies in insulin-treated patients; a clinical trial with highly purified insulins. Int. Congr. Ser. 316, 40–46 (1973).
  6. Institute of Medicine. Sources of Medical Technology: Universities and Industry (National Academies Press, 1995).
  7. Kurtzhals, P. et al. Multi-hexamer formation is the underlying basis for the ultra-long glucose-lowering effect of insulin degludec. Diabetologia 54, S426 (2011).
  8. Sharpey-Schäfer, E. A. An Introduction to the Study of the Endocrine Glands and Internal Secretions: Lane Medical Lectures, 1913 (Stanford Univ. Press, 1914).
  9. Katzung, B. G. M., Susan B. & Trevor, A. J. Basic & Clinical Pharmacology 12th edn (McGraw Hill, 2012).
  10. Padmore, E. Reflections on six decades of living with insulin-treated diabetes. J. Diabetes Nurs. 10, 366–370 (2009).
  11. Clothier, C. Living with diabetes in the 1950s. J. Diabetes Nurs. 23, 1–8 (2019).

Cited by

Sorted by citations

Related

Authors
Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A., & Evans-Molina, C.
Affiliations
  • Indiana University Indianapolis (US)
  • University of Exeter (GB)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-07
Volume
27
Issue
7
Pages
1154-1164
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-021-01418-2
PMC
PMC8802620
OpenAlex
W3182160338
Semantic Scholar
a166b2d1f5f5adcec32f90ad37ff2347946545ad
Cited by
270
References
153
Citations by year
2026: 46 · 2025: 71 · 2024: 64 · 2023: 58 · 2022: 22 · 2021: 9
FWCI
5.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01-BX001733)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01DK127786, R01 DK121929, R03 DK117253, R01 DK127308, R01DK093954, P30 DK097512, R21 DK119800)
  • National Center for Advancing Translational Sciences (UL1TR002529)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
insulin, insulin discovery, Banting and Best, type 1 diabetes, diabetes treatment, insulin pharmacokinetics, insulin delivery, diabetes pathophysiology
MeSH terms
Blood Glucose, Diabetes Mellitus, Type 1, Humans, Insulin

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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 by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-27.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-27.

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