Abstract
We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.
Highlights
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycaemia, which results from a combination of insulin resistance, increased hepatic glucose production and pancreatic β-cell dysfunction[1, 2]
We conducted the first prospective observational study in which we examine the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting plasma glucose levels 7 years later, in individuals who were non-diabetic at baseline
This study is the first prospective study to examine the association of incretin responses to an OGTT and MTT at baseline and the change in fasting plasma glucose during 7 years of follow-up, in individuals who were non-diabetic at baseline
Summary
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycaemia, which results from a combination of insulin resistance, increased hepatic glucose production and pancreatic β-cell dysfunction[1, 2]. Recent evidence indicated that the gastrointestinal system, especially the incretin hormones, play a significant role in the pathophysiology of T2DM as well[3]. The gastrointestinal incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are released from the gut into the bloodstream, where they bind to their specific receptors on the pancreas to regulate the amount of insulin and glucagon that is secreted to control blood glucose levels. The incretin effect accounts for at least 50%[6] and up to 70%, of the total insulin secreted after oral glucose intake and plays an important role in maintaining normal glucose regulation after meal intake[7, 8]. In T2DM patients, the incretin effect is severely reduced[9] and the impairment is thought to explain an important part of the impaired insulin secretion seen in T2DM[10]
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