ArticleDiabetologia2010
Impaired beta cell glucose sensitivity rather than inadequate compensation for insulin resistance is the dominant defect in glucose intolerance.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 118 citations in OpenAlex.
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- Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.Diabetes, obesity & metabolism · 2022Trial
- Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes.The Journal of clinical investigation · 2021Trial
- Dapagliflozin lowers plasma glucose concentration and improves β-cell function.The Journal of clinical endocrinology and metabolism · 2015Trial
- Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.Diabetes · 2011Trial
- Impact of positive family history and genetic risk variants on the incidence of diabetes: the Finnish Diabetes Prevention Study.Diabetes care · 2011Trial
- A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.Diabetologia · 2026Review
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- Impact of overweight and obesity on fasting insulin secretion in men and women without diabetes: effect sizes and mechanisms.Diabetologia · 2026Article
- Incretin system and glucagon secretion in patients with chronic pancreatitis.European journal of clinical investigation · 2025Article
- Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps.International journal of molecular sciences · 2025Review
- Comprehensive sequencing profile and functional analysis of IsomiRs in human pancreatic islets and beta cells.Diabetologia · 2025Article
- Hepatic Glucose Uptake During Euglycemic Hyperinsulinemia Associates With Glycemia During Oral Glucose Tolerance Test.Journal of the Endocrine Society · 2025Article
- Effects of Hypertriglyceridemia With or Without NEFA Elevation on β-cell Function and Insulin Clearance and Sensitivity.The Journal of clinical endocrinology and metabolism · 2025Article
- In-silico modelling of insulin secretion and pancreatic beta-cell function for clinical applications: is it worth the effort?Frontiers in clinical diabetes and healthcare · 2024Article
- Quantifying beta cell function in the preclinical stages of type 1 diabetes.Diabetologia · 2023Review
- Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study.Frontiers in endocrinology · 2023Article
- TyGIS: improved triglyceride-glucose index for the assessment of insulin sensitivity during pregnancy.Cardiovascular diabetology · 2022Article
- The Variation and Correlation of Serum Adiponectin, Nesfatin-1, IL-6, and TNF-α Levels in Prediabetes.Frontiers in endocrinology · 2022Article
- Association of NAFLD and Insulin Resistance with Non Metastatic Bladder Cancer Patients: A Cross-Sectional Retrospective Study.Journal of clinical medicine · 2021Article
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIt is commonly thought that hyperglycaemia results from insufficient compensation of insulin secretion for insulin resistance. To verify this hypothesis, we assessed beta cell function and insulin sensitivity (IS) in a large cohort of volunteers with normal glucose tolerance (NGT) or impaired glucose regulation (IGR), i.e. impaired glucose tolerance or impaired fasting glucose.
methodsIn men and women with NGT (n=1,123) or IGR(n=156) (age 44 +/- 8 years, BMI 25+/-4 kg/m2, mean +/- SD)we measured: (1) IS by clamp; (2) insulin secretion rates(ISR) and beta cell glucose sensitivity (=slope of the insulin secretion/plasma glucose dose-response) by C-peptide deconvolution and OGTT modelling; and (3) acute insulin response to intravenous glucose.
resultsAfter controlling for centre, sex, age and BMI, fasting and total ISR were inversely related to IS in both groups,whereas beta cell glucose sensitivity was not. Acute insulin response was reciprocally related to IS in both groups, but the relationships were incompatible with inadequate compensation and significance was lost after controlling for fasting ISR. InIGR vs NGT, IS was impaired (92 [75] vs 133 [86] micromol min(-1)[kg fat-free mass](-1) [nmol/l](-1), median [interquartile range],p<0.0001) as was beta cell glucose sensitivity (69 [46] vs 119[83] pmol min(-1) m(-2) [nmol/l](-1), p<0.0001), whereas fasting and total ISR were increased (35% and 25%, respectively, p<0.0001). In fully adjusted models, beta cell glucose sensitivity was the strongest determinant of OGTT glucose levels. CONCLUSIONS/
interpretationInsulin resistance normally upregulates the secretory tone, with no evidence of defective compensation in IGR. In contrast, beta cell glucose sensitivity is independent of insulin resistance, but a key determinant of glucose tolerance. This suggests that hyperglycaemia results from an intrinsic beta cell defect rather than from inadequate compensation for insulin resistance.
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