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Impaired beta cell sensitivity to incretins in type 2 diabetes is insufficiently compensated by higher incretin response

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BACKGROUND AND AIMS: The incretin effect is impaired in type 2 diabetes (T2D), but the underlying mechanisms are only partially understood. We investigated the relationships between the time course of the incretin effect and that of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during oral glucose tolerance tests (OGTTs), thereby estimating incretin sensitivity of the beta cell, and its associated factors.

METHODS AND RESULTS: Eight patients with T2D and eight matched subjects with normal glucose tolerance (NGT) received 25, 75, and 125 g OGTTs and corresponding isoglycemic glucose infusions (IIGI). The time course of the incretin effect, representing potentiation of insulin secretion by incretins (PINCR), was determined by mathematical modelling as the time-dependent fold increase in insulin secretion during OGTT compared to IIGI. The time course of PINCR was correlated with that of both GIP and GLP-1 in each subject (median r = 0.67 in NGT and 0.45 in T2D). We calculated an individual beta cell sensitivity to incretins (SINCR) using a weighted average of GIP and GLP-1 (pooled incretin concentration, PIC), as the slope of the relationship between PINCR and PIC. SINCR was reduced in T2D (p < 0.01). In the whole group, mean PIC, GIP and GLP-1 concentrations during the OGTT were inversely correlated with SINCR, but T2D had lower PIC, GIP and GLP-1 levels at the same SINCR (p < 0.05).

CONCLUSION: Relative incretin insensitivity is partly compensated for by higher incretin secretory responses. However, T2D shows both impairment in incretin sensitivity and abnormal compensation by incretin secretion.

Original languageEnglish
JournalNutrition, metabolism, and cardiovascular diseases : NMCD
Volume27
Issue number12
Pages (from-to)1123-1129
Number of pages7
ISSN0939-4753
DOIs
Publication statusPublished - Dec 2017

    Research areas

  • Aged, Biomarkers, Blood Glucose, Case-Control Studies, Denmark, Diabetes Mellitus, Type 2, Female, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Glucose Tolerance Test, Humans, Incretins, Insulin, Insulin-Secreting Cells, Male, Middle Aged, Models, Biological, Time Factors, Journal Article, Randomized Controlled Trial

ID: 52621307