The DOI matches its Crossref record; 152 of the 153 references it cites were found in a registry or an index; 50 of the 121 sources its claims cite were checked for support.
100 years of insulin: celebrating the past, present and future of diabetes therapy
Open accessAbstract
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.
Overview
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.
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Claims the paper makes
27 No full text of the sources · 25 Partly supported · 8 Own interpretation · 7 Supported · 5 Sources not found · 3 Supported so far · 2 Couldn’t confirm · 2 Not checked yet · 2 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Supportedcites [24] Bornstein, J. & Lawrence, R. Two types of diabetes mellitus, with and without available plasma insulin. Br. Med. J. 1, 732 (1951). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [3] Gale, E. A. The discovery of type 1 diabetes. Diabetes 50, 217–226 (2001). sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [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
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Could not verifycites [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). sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Could not verifycites [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). sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
- Supportedcites [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
The paper’s introductory text (in the supplied Abstract passage) states that more than 60% of candidate genes for type 1 diabetes are expressed in human pancreatic islets. That supports the citing sentence’s weaker claim of over 40% being expressed in the islet or beta cell. (LLM, conf=0.94)
- Supportedcites [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
The Results section reports that 25 of 41 (61%) candidate genes for type 1 diabetes were expressed in human islets, exceeding the claimed 40%. The paper also discusses beta-cell expression, though the quantified finding is for islets. Page numbers were not provided in the supplied copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [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
- Could not verifycites [59] Lee, H. et al. Beta cell dedifferentiation induced by IRE1α deletion prevents type 1 diabetes. Cell Metab. 31, 822–836 (2020). sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“since the turn of the century, increasing size and depth of genome-wide association studies have rapidly expanded the list of associated loci in type 2 diabetes to more than 250 with 400 independent signals79.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
The Results section, “Multiple association signals at T2D susceptibility loci” (page not provided), reports 403 significant T2D-association signals, supporting the approximate 400-signal figure. It reports 243 associated loci, however, not more than 250. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The majority of variants point towards the role of inflammation and the immune system in type 1 diabetes pathogenesis.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Could not verifycites [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). sourceExperimental — accuracy not yet measured
The Discussion’s Figure 3 caption describes a diabetes-mellitus query in the GWAS Catalog, but does not interpret type 1 diabetes variants. Searches for type 1 diabetes, inflammation, and immune-system involvement found no passage in our copy stating that a majority of the variants implicate those processes in pathogenesis. (LLM, conf=0.74)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
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In the paper
“Rosalyn Yalow and Solomon Berson’s development of a reliable radioimmunoassay allowed for direct measurement of insulin levels, allowing for the separation of insulin-deficient versus insulin-insensitive diabetes based on measurement of circulating insulin26.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [26] Yalow, R. S. & Berson, S. A. Immunoassay of endogenous plasma insulin in man. J. Clin. Invest. 39, 1157–1175 (1960). sourceExperimental — accuracy not yet measured
The Summary and Conclusion (p. 17) describes a sensitive immunoassay that measures plasma insulin directly. The discussion (p. 16) uses measured insulin in early maturity-onset diabetes to argue against absolute insulin deficiency, but treats impaired tissue response as one possible explanation. It does not establish a separation of insulin-deficient and insulin-insensitive forms of diabetes based on circulating insulin. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, birth cohort studies have shed light on the timing of autoantibody development, describing a wide range but a surprising peak incidence of islet autoantibody development at 9 months of age62, particularly focused on insulin autoimmunity.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Supportedcites [62] Krischer, J. P. et al. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 58, 980–987 (2015). source
The Results (page unavailable) report that islet-autoantibody incidence rose sharply until 9 months of age and declined thereafter. They also report that insulin autoantibodies alone were most frequent in the first year of life, whereas GADA alone rose later. The finding comes from the TEDDY birth cohort of genetically at-risk children. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
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In the paper
“The first associated loci, in genes including TCF7L2, INSR, IRS1, GCK and KCNJ11 (refs.77,78), were originally identified by linkage or candidate gene studies, and since the turn of the century, increasing size and depth of genome-wide association studies have rapidly expanded the list of associated loci in type 2 diabetes to more than 250 with 400 independent signals79.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [77] Duggirala, R. et al. Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans. Am. J. Hum. Genet 64, 1127–1140 (1999). sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that the authors used linkage analysis to identify a type 2 diabetes susceptibility region on chromosome 10q in Mexican Americans. That supports linkage as an early discovery approach, but the paper does not identify associated loci in TCF7L2, INSR, IRS1, GCK, or KCNJ11, or establish how those named loci were first identified. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
- It may state two separate claims as one. 32
- Probably not a substantial claim. 15
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [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
- Supportedcites [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
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [20] Pincus, G., Joslin, E. & White, P. The age-incidence relations in diabetes mellitus. Am. J. Med. Sci. 188, 116–121 (1934). source
- Partly supportedcites [21] MacLean, H. Some observations on diabetes and insulin in general practice. Postgrad. Med. J. 1, 73–77 (1926). sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
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In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [91] Berg, P. Fred Sanger: a memorial tribute. Proc. Natl Acad. Sci. USA 111, 883–884 (2014). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [92] Ryle, A. P., Sanger, F., Smith, L. F. & Kitai, R. The disulphide bonds of insulin. Biochem. J. 60, 541–556 (1955). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [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
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Supportedcites [3] Gale, E. A. The discovery of type 1 diabetes. Diabetes 50, 217–226 (2001). source
In “The Road to Autoimmune Diabetes,” Gale says earlier attempts to identify islet cell antibodies by indirect immunofluorescence failed before they were demonstrated in 1974. “Genetic Heterogeneity” identifies Bottazzo, working in Doniach’s laboratory, as the researcher who then observed islets lighting up under the microscope. Page numbers are not available in the supplied copy. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [5] Bottazzo, G., Florin-Christensen, A. & Doniach, D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 304, 1279–1283 (1974). source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Partly supportedcites [121] Oleck, J., Kassam, S. & Goldman, J. D. Commentary: why was inhaled insulin a failure in the market? Diabetes Spectr. 29, 180–184 (2016). sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
What the sources say
- Not checked — no full text of the sourcecites [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
- Partly supportedcites [101] Liu, M. et al. Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant diabetes. Diabetes 61, 828–837 (2012). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Not checked — no full text of the sourcecites [122] Kovatchev, B. A century of diabetes technology: signals, models, and artificial pancreas control. Trends Endocrinol. Metab. 30, 432–444 (2019). source
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Closing.
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In 1985 the first insulin pen was launched by Novo Nordisk120.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Supportedcites [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 section states that the first insulin pen, the NovoPen, was launched by Novo Nordisk in 1985. This directly supports the cited sentence. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [8] Cudworth, A. G. & Woodrow, J. C. HL-A antigens and diabetes mellitus. Lancet 2, 1153 (1974). source
- Not checked — no full text of the sourcecites [46] Gottlieb, M. S. & Root, H. F. Diabetes mellitus in twins. Diabetes 17, 693–704 (1968). source
- Not checked — no full text of the sourcecites [47] Tattersall, R. B. & Pyke, D. A. Diabetes in identical twins. Lancet 2, 1120–1125 (1972). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin
What the sources say
- Not checked — no full text of the sourcecites [4] Bliss, M. The history of insulin. Diabetes Care 16, 4–7 (1993). source
- Not matchedcites [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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [80] McCarthy, M. I. Genomics, type 2 diabetes, and obesity. N. Engl. J. Med. 363, 2339–2350 (2010). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [45] Eisenbarth, G. S. Type I diabetes mellitus. A chronic autoimmune disease. N. Engl. J. Med. 314, 1360–1368 (1986). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin
What the sources say
- Not checked — no full text of the sourcecites [4] Bliss, M. The history of insulin. Diabetes Care 16, 4–7 (1993). source
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [23] Himsworth, H. P. Diabetes mellitus: its differentiation into insulin-sensitive and insulin insensitive types. Lancet 227, 127–130 (1936). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [38] Gepts, W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14, 619–633 (1965). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the understanding of diabetes pathophysiology.
What the sources say
- Not checked — no full text of the sourcecites [42] National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28, 1039–1057 (1979). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there are continued challenges with accessibility and equity, which have only been exacerbated by advances in diabetes care technology.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Closing.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Not checked — no full text of the sourcecites [105] Ovalle, F. et al. Understanding concentrated insulins: a systematic review of randomized controlled trials. Curr. Med. Res. Opin. 34, 1029–1043 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In 1968, Ronald Chance at Lilly Research Laboratories in Indianapolis published the porcine sequence of the proinsulin molecule96.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
What the sources say
- Not checked — no full text of the sourcecites [96] Chance, R. E., Ellis, R. M. & Bromer, W. W. Porcine proinsulin: characterization and amino acid sequence. Science 161, 165–167 (1968). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > What does the future hold?
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the subsequent discoveries that have improved life expectancy and quality of life for those with diabetes (Fig. 3)”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Closing.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Altered interaction of structurally abnormal insulin with the insulin receptor leads to altered insulin action, hyperinsulinemia and adult-onset diabetes with autosomal dominant inheritance98.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
What the sources say
- Not checked — no full text of the sourcecites [98] Shoelson, S. et al. Three mutant insulins in man. Nature 302, 540–543 (1983). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > What does the future hold?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Closing.
What the sources say
- Not checked — no full text of the sourcecites [1] Bliss, M. The Discovery of Insulin (Univ. Chicago Press, 1982). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition to being the first protein that was successfully sequenced, insulin was the first molecule to be characterized as a prohormone.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the molecular characterization of insulin.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Not matchedcites [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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“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.”
§ 100 years of insulin: celebrating the past, present and future of diabetes therapy > The discovery of insulin > Advances in the clinical use of insulin.
What the sources say
- Not matchedcites [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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
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.”
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“The peptide hormone insulin has been the subject of intense research since its discovery by Banting and Best over 100 years ago, with profound medical implications 1 .”
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“On the other hand, insulin has the ability to inhibit gluconeogenesis, lipolysis, apoptosis, and autophagy [2,3].”
BackgroundPrecision medicine in type 1 diabetes
Carr, A. L. J., Evans‐Molina, C., & Oram, R. A. (2022) · Diabetologia · doi:10.1007/s00125-022-05778-3 · Cited by 69
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“Despite advances over the past decades, including improved life expectancy and quality of life [1], in 2021 alone, diabetes mellitus, a metabolic disorder primarily characterized by high blood glucose (BG) levels, affected 537 million people globally.”
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“As the world embarks on a centennial anniversary since the development of insulin to manage glucose levels of people with diabetes, we have seen remarkable advances during these 100 years, with improved life expectancy and quality of life [2].”
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“Currently, insulin is primarily administered through subcutaneous injections [45].”
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“For example, glutamic acid can be used to treat epilepsy, neuras-thenia and other diseases [54], while insulin as a peptide biopharmaceutical has been widely used in the treatment of diabetes [55].”
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“It is worth mentioning that not until 1951 was insulin fully sequenced by Frederick Sanger [19], and bovine insulin was successfully chemically synthesized in the mid-1960s [16,20,21].”
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“The therapeutic market started 100 years ago using insulin to treat type 1 diabetes [8, 9].”
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“As early as 1500 BC, the existence of diabetes was first mentioned by the Egyptians [25], [26].”
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“Particularly, the utilization of this animal model has greatly contributed to significant advancements in comprehending the structure and function of the pancreas, with a particular emphasis on the discovery and molecular mechanisms of insulin [8].”
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“Oral insulin mimics the normal insulin absorption pathway to establish a portal-peripheral insulin gradient, which avoids peripheral hyperinsulinemia raised by frequent subcutaneous injections [3].”
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“This resistance, in turn, increases the risk of chronic metabolic diseases, such as diabetes [23], hypertension [24], and hyperlipidemia [25].”
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“It is secreted by β -cells when serum glucose reaches a certain threshold [1,2].”
A perspective on treating type 1 diabetes mellitus before insulin is needed
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A brain-derived insulin signal encodes protein satiety for nutrient-specific feeding inhibition
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“Protamine is used in clinical practice to reverse high-dose heparin anticoagulation in cardiovascular procedures and to stabilize insulin, indicating LMWP is well tolerated in humans 34,35 .”
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“The inclusion criteria were as follows: (1) patients who met the 1999 World Health Organization (WHO) diagnostic criteria for diabetes; (2) insulin-dependent diagnosis for T1DM; and (3) patients who were treated with intensive insulin therapy administered by either CSII or MDI, in form of 4 or more insulin injections…”
BackgroundMethodNatural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review
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Self-citation
Metadata
- 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)
- Venue
- Nature Medicine
- Published
- 2021-07
- Volume
- 27
- Issue
- 7
- Pages
- 1154-1164
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- 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
- green
- www.ncbi.nlm.nih.gov
- 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 › Endocrinology, Diabetes and Metabolism › 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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