Insulin clearance and incretin hormones following oral and \u201cisoglycemic\u201d intravenous glucose in type 2 diabetes patients under different antidiabetic treatments

Andrea Tura,Christian Göbl,Giovanni Pacini,Michael Nauck,Irfan Vardarli

doi:10.1038/s41598-022-06402-5

Abstract

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D). We aimed exploring possible associations between insulin clearance and endogenously secreted or exogenously administered incretins in T2D patients. Twenty T2D patients were studied (16 males/4 females, 59 ± 2 years (mean ± standard error), BMI = 31 ± 1 kg/m2, HbA1c = 7.0 ± 0.1%). Patients were treated with metformin, sitagliptin, metformin/sitagliptin combination, and placebo (randomized order). On each treatment period, oral and isoglycemic intravenous glucose infusion tests were performed (OGTT, IIGI, respectively). We also studied twelve T2D patients (9 males/3 females, 61 ± 3 years, BMI = 30 ± 1 kg/m2, HbA1c = 7.3 ± 0.4%) that underwent infusion of GLP-1(7–36)-amide, GIP, GLP-1/GIP combination, and placebo. Plasma glucose, insulin, C-peptide, and incretins were measured. Insulin clearance was assessed as insulin secretion to insulin concentration ratio. In the first study, we found OGTT/IIGI insulin clearance ratio weakly inversely related to OGTT/IIGI total GIP and intact GLP-1 (R2 = 0.13, p < 0.02). However, insulin clearance showed some differences between sitagliptin and metformin treatment (p < 0.02). In the second study we found no difference in insulin clearance following GLP-1 and/or GIP infusion (p > 0.5). Thus, our data suggest that in T2D there are no relevant incretin effects on insulin clearance. Conversely, different antidiabetic treatments may determine insulin clearance variations.

Highlights

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D)
We found that insulin clearance reduction in oral glucose tolerance test (OGTT) vs. isoglycemic intravenous glucose infusion (IIGI) shows some associations to plasma incretin levels
The associations were significant only for total GIP and for intact GLP-1 in multivariable statistical analysis, and, more importantly, the associations were weak. This suggests that the effect of incretins on insulin clearance is small or negligible, and other factors should have a higher impact in determining the insulin clearance reduction following OGTT vs. IIGI

Summary

Introduction

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D). Alterations in insulin clearance may appear already in the prediabetes states, showing a tendency to decrease when subjects progress towards dysglycemia and possibly type 2 diabetes[6]. There is evidence that insulin clearance is reduced following oral compared to intravenous glucose administration. This was shown in some pioneering studies already some decades ago, with an emphasis on changes in hepatic insulin clearance[11,12,13,14,15]. Even in more recent studies, the quantification of insulin clearance reduction after oral vs intravenous glucose administration in type 2 diabetes has not been extensively e xamined[16,17]. Previous s tudies[18,19,20,21] did not include participants with type 2 diabetes

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Conclusion