Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state?
Filip K. Knop,Tina Vilsbøll,Patricia V. Højberg,Steen Larsen,Sten Madsbad,Aage Vølund,Jens J. Holst,Thure Krarup +7 more
TLDR
The results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.Abstract:
We aimed to investigate whether the reduced incretin effect observed in patients with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or a consequence of the diabetic state. Eight patients with chronic pancreatitis and secondary diabetes (A1C mean [range] of 6.9% [6.2-8.0]), eight patients with chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9-5.7]), eight patients with type 2 diabetes (6.9 [6.2-8.0]); and eight healthy subjects (5.5 [5.1-5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50-g oral glucose load and an isoglycemic intravenous glucose infusion, respectively. The incretin effect (100% x [beta-cell secretory response to oral glucose tolerance test - intravenous beta-cell secretory response]/beta-cell secretory response to oral glucose tolerance test) was significantly (P < 0.05) reduced (means +/- SE) in patients with chronic pancreatitis and secondary diabetes (31 +/- 4%) compared with patients with chronic pancreatitis and NGT (68 +/- 3) and healthy subjects (60 +/- 4), respectively. In the type 2 diabetes group, the incretin effect amounted to 36 +/- 6%, significantly (P < 0.05) lower than in chronic pancreatitis patients with NGT and in healthy subjects, respectively. These results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.read more
Citations
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The Role of Incretins in Glucose Homeostasis and Diabetes Treatment
Wook Kim,Josephine M. Egan +1 more
TL;DR: Two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in type 2 diabetes (T2DM) and an incretIn enhancer (sitagliptin, which is a DPP4 inhibitor).
Journal ArticleDOI
Mechanisms of diabetes mellitus-induced bone fragility
TL;DR: Factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism, as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.
Journal ArticleDOI
The incretin system and its role in type 2 diabetes mellitus.
TL;DR: The reduced incretin effect is believed to contribute to impaired regulation of insulin and glucagon secretion in T2DM, and, in support of this, exogenous GLP-1 administration may restore blood glucose regulation to near normal levels.
Journal ArticleDOI
Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?
TL;DR: Factors are identified that may determine individual incretin secretory responses and explain some of the variations in published findings of group differences in GLP-1 responses to nutrient intake that do not support the contention of a generalised defect in nutrient-related GLp-1secretory responses in type 2 diabetes patients.
Journal ArticleDOI
Incretin hormones: Their role in health and disease.
Michael A. Nauck,Juris J. Meier +1 more
TL;DR: However, the insulinotropic and glucagonostatic effects of GLP-1 are preserved in subjects with type 2 diabetes to the degree that pharmacological stimulation of the glucagon-like peptide-1 receptors significantly reduces plasma glucose and improves glycaemic control.
References
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TL;DR: The measurement of intact incretin hormones revealed that total as well as intact GIP responses were minimally decreased in patients with type 2 diabetes, whereas the late intact GLP-1 response was strongly reduced, supporting the hypothesis that an impaired function of GLp-1 as a transmitter in the enteroinsular axis contributes to the inappropriate insulin secretion in type 2 diabetic patients.
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TL;DR: Both amidated and glycine-extended GLP-I molecules are produced in the small intestine and in the pancreas in humans and both are measurable in fasting plasma.