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Cited by 1,743Diabetes Treatment and ManagementPancreatic function and diabetesDiabetes, Cardiovascular Risks, and Lipoproteins

Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future

Open access
Kahn, Steven E, Cooper, Mark E, Del Prato, Stefano·2014·The Lancet
DOI 10.1016/s0140-6736(13)62154-6PMC PMC4226760
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Abstract

Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(13)62154-6

Cites

224 of 224 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 100 cited sources checked · 0 supported · 0 flagged

  • Interpretationreasoning

    When insulin resistance is present, the β-cell increases insulin output to maintain normal glucose tolerance.

    “When insulin resistance is present, as seen most commonly with obesity, the β-cell increases its insulin output to maintain normal glucose tolerance (Figure 1B).”
    Quote in the paperSubstantial claim
  • Premisecitation

    A proportion of these abnormalities are explained by adiposity, especially intra-abdominal.

    “a proportion of these abnormalities are explained by adiposity, especially that located within the intra-abdominal cavity6.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Cnop, 2002, The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments, Diabetes source

      Not checked in the free run.

  • Interpretationreasoning

    When the β-cell cannot increase insulin output sufficiently in the presence of insulin resistance, plasma glucose rises.

    “However, when the β-cell is incapable of this task, the result is an elevation in plasma glucose (Figure 1C).”
    Quote in the paperSubstantial claim
  • Premisecitation

    Insulin resistance is already well established when impaired glucose tolerance is present.

    “Insulin resistance is already well established when impaired glucose tolerance is present”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Stancáková, 2009, Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men, Diabetes source

      Not checked in the free run.

  • Premisecitation

    β-cell function is heritable.

    “Further, it has been shown that β-cell function is heritable16 and critically determines glucose intolerance and type 2 diabetes in different racial and ethnic groups17.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Elbein, 1999, Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds, J Clin Endocrinol Metab

      Not checked in the free run.

  • May combine two claims. 32
  • Classified as probably not a substantial claim. 1

  • May combine two claims.

    Premisecitation

    Individuals with early maturity onset diabetes produce insulin and secrete it in response to nutrient ingestion.

    “individuals with “early maturity onset diabetes” produced insulin and secreted this hormone in response to nutrient ingestion2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Yalow, 1960, Immunoassay of endogenous plasma insulin in man, J Clin Invest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Insulin insensitivity contributes to increased hepatic glucose production and decreased glucose uptake in muscle and adipose tissue.

    “this contributed to increased glucose production by the liver and decreased glucose uptake in muscle and adipose tissue5.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Reaven, 1988, Banting lecture 1988. Role of insulin resistance in human disease, Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The disturbances of prediabetes and diabetes are a continuum in which the magnitude of β-cell function reduction determines the degree of plasma glucose elevation.

    “the reality is that these disturbances are a continuum in which the magnitude of the reduction in β-cell function determines the degree of elevation in plasma glucose.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The basis for β-cell loss is multifactorial, including glucolipotoxicity and amyloid deposition causing apoptosis through oxidative and ER stress.

    “The basis for this loss is multifactorial, and includes glucolipotoxicity32 and amyloid deposition that result in β-cell apoptosis through oxidative as well as endoplasmic reticulum stress31.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] Jurgens, 2011, β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition, Am J Pathol source

      Not checked in the free run.

    • cites [32] Poitout, 2008, Glucolipotoxicity: fuel excess and β-cell dysfunction, Endocr Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Together these genes do not explain much of the genetic basis of type 2 diabetes; genotype risk scores only slightly improve prediction compared to common clinical risk factors.

    “Together these genes do not appear to explain much of the genetic basis of the disease with the use of genotype risk scores only slightly improving prediction of subsequent diabetes compared to common clinical risk factors22,23.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Meigs, 2008, Genotype score in addition to common risk factors for prediction of type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [23] Lyssenko, 2008, Clinical risk factors, DNA variants, and the development of type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The vast majority of type 2 diabetes gene loci are linked to the β-cell, while a few are associated with obesity and insulin resistance.

    “While a few loci are associated with obesity and insulin resistance, the vast majority are linked to the β-cell21.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] McCarthy, 2010, Genomics, type 2 diabetes, and obesity, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The disease process of type 2 diabetes is heterogeneous, including other pathogenic factors.

    “it is clear that the disease process is heterogeneous, including other pathogenic factors discussed subsequently.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Obesity is frequently characterized by systemic inflammation, and preclinical evidence links systemic inflammation to β-cell dysfunction.

    “Obesity is frequently characterized by systemic inflammation and preclinical evidence links systemic inflammation to β-cell dysfunction63,64.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [63] Dula, 2010, Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling, Cell Calcium source

      Not checked in the free run.

    • cites [64] Nicol, 2013, Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates, J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bile acids are endogenous ligands of FXR, and their activation results in release of FGF19.

    “They are endogenous ligands of the farnesoid X receptor (FXR), their activation of FXR resulting in the release of fibroblast growth factor (FGF) 1943.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Potthoff, 2012, Endocrine fibroblast growth factors 15/19 and 21: from feast to famine, Genes Dev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GLP-1 is the more important incretin acting on both β- and α-cells to enhance insulin and suppress glucagon secretion.

    “GLP-1 is the more important of these hormones acting on both β- and α-cells to enhance insulin and suppress glucagon secretion, respectively37.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Drucker, 2006, The biology of incretin hormones, Cell Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Direct effects of inflammation on β-cells arise from activation of the intra-islet immune response, with strongest support for IL-1β.

    “Direct effects of inflammation on β-cells arise from activation of the intra-islet immune response, the strongest support being for a role for interleukin-1β (IL-1β)71.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Donath, 2003, Inflammatory mediators and islet β-cell failure: a link between type 1 and type 2 diabetes, J Mol Med (Berl) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ACCORD, the patients at greatest risk of adverse outcomes from aggressive glucose lowering had longer diabetes duration, poor glucose control at start of intensive insulin therapy, and no immediate glucose lowering response.

    “Analyses from ACCORD suggest that the individual likely to be at greatest risk of an adverse outcome to aggressive glucose lowering had a longer duration of diabetes, poor glucose control at the time of commencing intensive insulin therapy, and did not demonstrate an immediate glucose lowering response125.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Gelling, 2003, Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice, Proc Natl Acad Sci USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Look AHEAD, an intensive lifestyle intervention failed to lower cardiovascular events relative to diabetes support and education, even though it produced sustained weight loss over 10 years and improved several cardiovascular risk factors.

    “Despite differential weight loss for over 10 years and improvements in many cardiovascular risk factors, including blood pressure and lipids, lifestyle change did not reduce cardiovascular events compared to diabetes support and education (control)133.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [133] Adams, 2013, LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Steno 2 Study found that a multifactorial intervention lowered both cardiovascular and microvascular events, with the benefit persisting after the initial glucose, blood pressure, and lipid treatments were stopped.

    “consistent with the multifactorial approach in the Steno 2 Study that demonstrated a reduction in both cardiovascular and microvascular events which was sustained even after cessation of the initial glucose, blood pressure and lipid lowering regimens132.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [132] Kliewer, 2010, Fibroblast growth factor 21: from pharmacology to physiology, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ADVANCE, microvascular benefit was shown, with magnitude related to degree of glucose control and affecting largely renal outcomes (reduction in microalbuminuria).

    “Such a microvascular benefit was also shown in ADVANCE, the magnitude being related to the degree of glucose control and affecting largely renal outcomes (essentially a reduction in microalbuminuria)124.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Talchai, 2012, Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure, Cell source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Across five studies, intensifying glucose control appears beneficial for microvascular complications but ineffective for cardiovascular events, and possibly harmful in advanced type 2 diabetes.

    “Thus, based on five separate studies, it would seem that current approaches involving intensification of glucose control are valuable for reducing microvascular complications but are not effective in reducing cardiovascular events, possibly even being harmful in those with advanced type 2 diabetes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    In Look AHEAD, large proportions of subjects in both groups received medical treatment for risk factors, which may explain the lack of cardiovascular benefit.

    “This may have been because large proportions of subjects in both groups received medical treatment for these risk factors.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In type 2 diabetic patients, serum after glargine treatment activates insulin receptors A and B to a similar extent as NPH insulin and does not enhance IGF-1 receptor signalling.

    “serum from type 2 diabetic patients treated with glargine activates insulin receptors A and B similarly to NPH insulin and does not increase signalling through the IGF-1 receptor128.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [128] Agius, 2007, New hepatic targets for glycaemic control in diabetes, Best Pract Res Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ADOPT, onset of glucose lowering with metformin and rosiglitazone was slower, but most sustained with rosiglitazone, with metformin intermediate.

    “Whereas the onset of glucose lowering with the other two medications was slower, it was most sustained with rosiglitazone, with metformin demonstrating an intermediate pattern.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [138] Lindsay, 2003, Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ADOPT, glibenclamide produced the greatest initial reduction in glycaemia but was poorest in maintaining glucose control.

    “Glibenclamide produced the greatest initial reduction in glycaemia, but was poorest in maintaining glucose control.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [138] Lindsay, 2003, Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies testing lifestyle and drug interventions to delay diabetes onset have generally shown benefit, with lifestyle outperforming all medications except thiazolidinediones.

    “These trials have more or less uniformly demonstrated a benefit, with lifestyle more efficacious than all medications with the exception of the thiazolidinediones140–152.”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [140] Gathercole, 2013, 11β-hydroxysteroid dehydrogenase 1: translational and therapeutic aspects, Endocr Rev source

      Not checked in the free run.

    • cites [141] Tschöp, 2012, Outstanding Scientific Achievement Award Lecture 2011: defeating diabesity: the case for personalized combinatorial therapies, Diabetes source

      Not checked in the free run.

    • cites [142] Tan, 2013, Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia, Diabetes source

      Not checked in the free run.

    • cites [143] 1998, 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 source

      Not checked in the free run.

    • cites [144] Gerstein, 2008, Effects of intensive glucose lowering in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [145] Duckworth, 2009, Glucose control and vascular complications in veterans with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [146] Gerstein, 2012, Basal insulin and cardiovascular and other outcomes in dysglycemia, N Engl J Med source

      Not checked in the free run.

    • cites [147] Patel, 2008, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [148] Riddle, 2010, Epidemiologic relationships between A1C and all-cause mortality during a median 3·4-year follow-up of glycemic treatment in the ACCORD trial, Diabetes Care source

      Not checked in the free run.

    • cites [149] Ismail-Beigi, 2010, Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Intensive lifestyle change in type 2 diabetes yields benefits but does not improve cardiovascular outcomes, which are still the leading cause of premature death in this condition.

    “Thus, intensive lifestyle change in patients with type 2 diabetes has benefits, but unfortunately not on cardiovascular outcomes which remain the major determinant of premature mortality in type 2 diabetes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cardiovascular outcomes remain the major determinant of premature mortality in type 2 diabetes.

  • May combine two claims.

    Premisecitation

    In youth with type 2 diabetes, both microalbuminuria and retinopathy increase with diabetes duration, and severity is related to glycaemic control.

    “Both microalbuminuria and retinopathy increase with diabetes duration and severity is related to glycaemic control163,164.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [163] Pan, 1997, Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study, Diabetes Care source

      Not checked in the free run.

    • cites [164] Tuomilehto, 2001, Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SAVOR-TIMI 53 and EXAMINE showed no increased risk of cardiovascular events with the DPP-4 inhibitors saxagliptin and alogliptin.

    “The results of SAVOR-TIMI 53 (NCT01107886) and EXAMINE (NCT00968708) were recently released and showed no increased risk of cardiovascular events with the DPP-4 inhibitors saxagliptin96 and alogliptin97, respectively.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [96] Scirica, 2013, Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus, N Engl J Med source

      Not checked in the free run.

    • cites [97] White, 2013, Alogliptin after acute coronary syndrome in patients with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Type 2 diabetes in youth seems to progress more aggressively than in adults, and the differing effects of interventions stem from a larger improvement in β-cell function.

    “The disease’s course in youth appears to be more aggressive than in adults, with the differential impact of the interventions being the result of a greater improvement in β-cell function160.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [160] Rejeski, 2012, Lifestyle change and mobility in obese adults with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In SAVOR-TIMI 53 and EXAMINE, the number of pancreas-related events was too small to be definitive, but there was no evidence for a marked excess of such events with either medication.

    “While the number of pancreas-related events in SAVOR-TIMI 53 and EXAMINE were too small to be definitive, there was no evidence for a marked excess of such events with either medication.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [96] Scirica, 2013, Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus, N Engl J Med source

      Not checked in the free run.

    • cites [97] White, 2013, Alogliptin after acute coronary syndrome in patients with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Despite good rationale for approval of interventions to delay onset of diabetes, no medication has yet received official sanction as a preventative treatment.

    “However, despite good rationale for approval of interventions to delay the onset of diabetes159, no medication has yet received official sanction as a preventative treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Foster, 2009, A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study, Arch Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In youth with type 2 diabetes, dyslipidaemia and hypertension are common and worsen over time.

    “Further analyses from TODAY show that in youth with type 2 diabetes dyslipidaemia162 and hypertension163 are common and worsen over time.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [162] Bunck, 2011, Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes, Diabetes Care source

      Not checked in the free run.

    • cites [163] Pan, 1997, Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In children, type 2 diabetes pathogenesis is critically driven by loss of β-cell function, and residual β-cell function determines glucose control in those recently diagnosed.

    “The pathogenesis of the syndrome in children is also critically determined by β-cell function loss with the degree of residual β-cell function determining glucose control in recently diagnosed patients160.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [160] Rejeski, 2012, Lifestyle change and mobility in obese adults with type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the TODAY study, glycaemia in youth with type 2 diabetes was best managed by the combination of rosiglitazone and metformin, with the addition of lifestyle to metformin being no better than metformin alone.

    “The TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study examined the impact of lifestyle and medications in a young cohort with diabetes duration of less than a year and found glycaemia to be best managed by the combination of rosiglitazone and metformin, with the addition of lifestyle to metformin being no better than metformin alone161.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Kahn, 2006, Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Given that current treatment approaches do not prevent or slow the loss of β-cell function, there is an urgent need for alternative approaches.

    “Given that current treatment approaches do not prevent or slow the loss of β-cell function, there is clearly an urgent need for alternative approaches.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Type 2 diabetes is a progressive disease driven by advancing β-cell dysfunction.

  • May combine two claims.

    Premisecitation

    Current treatment algorithms are less prescriptive than before and advocate a more personalized approach to the choice of medications and treatment targets for type 2 diabetes.

    “While current treatment algorithms are less prescriptive than before and advocate a more personalized approach to the choice of medications and treatment targets for type 2 diabetes131”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [131] Ma, 2011, PTP1B inhibitor improves both insulin resistance and lipid abnormalities in vivo and in vitro, Mol Cell Biochem source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    In the Swedish Obese Subjects Study, subjects were not randomized, the control group was contemporaneously matched, only received conventional treatment, and differed by a number of characteristics at baseline.

    “However, these hypotheses are based on results from the Swedish Obese Subjects Study in which subjects were not randomized and the control group was contemporaneously matched, only received conventional treatment, and differed by a number of characteristics at baseline.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [173] Gerstein, 2006, Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial, Lancet source

      Not checked in the free run.

    • cites [174] DeFronzo, 2011, Pioglitazone for diabetes prevention in impaired glucose tolerance, N Engl J Med source

      Not checked in the free run.

    • cites [175] Zinman, 2010, Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study, Lancet source

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    The human gene pool has not changed in recent times.

    “As our gene pool has not changed in recent times, environmental changes have been critical in determining the type 2 diabetes epidemic.”

  • The paper relies on this without support.

    The reduction in β-cell mass in type 2 diabetes is insufficient to explain the degree of impairment in insulin release.

    “While a reduction in β-cell mass exists in type 2 diabetes, it is clear that the magnitude of this abnormality is insufficient to explain the degree of impairment in insulin release.”

  • The paper relies on this without support.

    The current treatment armamentarium does not readily attain and maintain normal glucose levels as β-cell function progressively declines.

    “As the current treatment armamentarium does not readily attain and maintain normal glucose levels as β-cell function progressively declines, new and novel approaches are being developed.”

  • The paper relies on this without support.

    Type 2 diabetes is a progressive disease driven by advancing β-cell dysfunction.

    “As type 2 diabetes is a progressive disease due to advancing β-cell dysfunction”

  • The paper relies on this without support.

    People with impaired glucose tolerance and/or impaired fasting glucose are at high risk of developing type 2 diabetes.

    “Slowing disease progression has also focused on individuals with impaired glucose tolerance and/or impaired fasting glucose because of their high risk of developing type 2 diabetes.”

  • The paper relies on this without support.

    Current treatment algorithms are based largely on industry-conducted studies that typically compare no more than two medications and are short term.

    “Current treatment algorithms are based largely on industry-conducted studies, which typically do not compare more than two medications and are short term.”

  • The paper relies on this without support.

    Cardiovascular outcomes remain the major determinant of premature mortality in type 2 diabetes.

    “which remain the major determinant of premature mortality in type 2 diabetes.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. 1970, A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes: I. Design, methods and baseline results, Diabetes, 19, 747

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Related

Authors
Kahn, S. E., Cooper, M. E., & Del Prato, S.
Affiliations
  • University of Washington (US)
  • Baker Heart and Diabetes Institute (AU)
Corresponding author
Kahn, Steven E
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2014-03
Volume
383
Issue
9922
Pages
1068-1083
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(13)62154-6
PMC
PMC4226760
OpenAlex
W2153399820
Cited by
1,743
References
224
Citations by year
2026: 88 · 2025: 129 · 2024: 141 · 2023: 162 · 2022: 159 · 2021: 184 · 2020: 169 · 2019: 157 · 2018: 151 · 2017: 123 · 2016: 137 · 2015: 97 · 2014: 41 · 2013: 2 · 2012: 1
FWCI
13.66
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders
  • Ministero dell’Istruzione, dell’Università e della Ricerca
  • National Institutes of Health (DK-017047)
  • U.S. Department of Veterans Affairs
  • National Health and Medical Research Council (2010YK7Z5K_006)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, insulin resistance, beta-cell dysfunction, glucose metabolism, insulin secretion, glucose tolerance, gut microbiota, fatty acids, amino acids, hexoses, diabetes prevention, diabetes treatment, bariatric surgery
MeSH terms
Diabetes Mellitus, Type 2, Glucose, Humans, Inflammation, Insulin, Insulin Resistance, Obesity, Genetic Predisposition to Disease, Epigenesis, Genetic, Bariatric Surgery, Glucagon-Secreting Cells, Insulin-Secreting Cells, Gene-Environment Interaction

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