The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Abstract

Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n = 31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n = 68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20 +/- 3 pmol/l to a peak of 68 +/- 5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27 +/- 3 pmol/l to a higher peak value of 104 +/- 6 pmol/l at 30 min (p less than 0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30-90 min (p less than 0.01-0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22 +/- 4 pmol/l to a peak of 93 +/- 6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25 +/- 2 pmol/l to a higher peak of 133 +/- 7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p less than 0.001), 60 min (p less than 0.01) and from 210-240 min (p less than 0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.

Incretin levels in polycystic ovary syndrome

“…The observed discrepancies between the present results and those of the cited investigation (14) could be due to either the limited sample size of the previous study or the methodological differences in the incretin hormone assays. Our results do on the other hand accord with other authors, describing increased GIP (20) and decreased active GLP-1 levels in patients with overt T2DM (21). Similarly, increased total and intact GIP levels accompanied by increased C-peptide levels have been shown in subjects with impaired glucose tolerance (22).…”

WNT/β-catenin increases the production of incretins by entero-endocrine cells

“…And in streptozotocin-induced diabetic rats, enhanced Gip gene expression and elevated serum levels induced chronic desensitisation of GIP receptor in vivo [2]. Finally, human diabetic and/or obese patients have increased plasma GIP levels after an oral load of glucose [45] and increased fasting responses to GIP [46,47]. Moreover, insulinotropic effects of GIP are lost in type 2 diabetes patients and their first-degree relatives [48,49], while GLP-1 response is conserved.…”

Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

“…Studies that directly compared GLP-1 responses following oral glucose vs mixed meal are scarce and the available studies did not find an altered GLP-1 response after both interventions among diabetic patients (7). GIP responses were found to be reduced (8), increased (7,9), but mostly unchanged in patients with diabetes (10,11,12,13). Possible explanations for these inconclusive findings on incretin responses among diabetic patients may relate to the assay used, the test meal, participant characteristics and probably sample size.…”