Abstract 16936: The Glucagon-Like Peptide 1 Response to Oral Glucose Tolerance Testing is Associated with Coronary Artery Calcium in Type 2 Diabetes Mellitus

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is characterized by decreased incretin effect and a blunted incretin response to meals. Whether the response of the incretin hormone glucagon-like peptide (GLP)-1 in oral glucose tolerance testing (OGTT) has utility for assessing the risk of T2DM macrovascular complications is not well known. We hypothesized that the GLP-1 response to OGTT is associated with coronary artery calcium (CAC), a marker of coronary atherosclerosis, in the Penn Diabetes Heart Study, a cross-sectional study of T2DM patients free of clinical cardiovascular or renal disease.

Methods: A subset of participants (N=596, mean age 59 ± 8 years, mean BMI 33 ± 6 kg/m², 68% male, 60% Caucasian, median T2DM duration 6 years) underwent 75 g OGTT with measurement of active GLP-1 by ELISA in plasma collected at 0, 30, 60, and 120 min. We calculated GLP-1 peak and net area under the curve (ΔAUC). At the same visit, Agatston CAC scores were quantified from electron beam tomography. Tobit regression was used to analyze cross-sectional associations between CAC and the top vs. bottom quintile for GLP-1 responses.

Results: At baseline, women had higher GLP-1 levels than men (p=0.03). GLP-1 ΔAUC and peak differed by both race and gender, with a greater response in women and African-Americans (all p<0.05). In Tobit regression models, there was a significant interaction by duration of diabetes in the association of CAC and GLP-1 responses. For subjects with T2DM duration > 6 years, although baseline GLP-1 was not associated with CAC, there was a significant positive association between CAC and the top vs. bottom quintile for both GLP-1 ΔAUC (Tobit ratio 1.45, 95% CI 0.36 [[Unable to Display Character: &#8211;]] 2.53, p<0.01) and peak GLP-1 (Tobit ratio 1.54, 95% CI 0.47 [[Unable to Display Character: &#8211;]] 2.62, p<0.01) after adjustment for cardiovascular risk factors and medications. In contrast, there was no significant association between CAC and baseline, ΔAUC, or peak GLP-1 for subjects with T2DM duration ≤ 6 years.

Conclusions: We demonstrate that an increased GLP-1 response to OGTT is associated with subclinical atherosclerosis in subjects with a longer duration of T2DM. Additional investigation is needed to identify the mechanism and determine if these findings translate into meaningful differences for cardiovascular risk prediction.