1297-P: Hypergliptinemia —A Compensatory Phenomenon Observed in Asian Population with Newly Diagnosed Type 2 Diabetes Mellitus

Introduction & Objective: Impaired glucagon-like peptide-1 (GLP-1) secretion in Western patients contributes to the incretin defect in type 2 diabetes mellitus (T2DM). However, several studies from East Asia suggested preserved GLP-1 levels in T2DM. We aimed to resolve these conflicting findings by investigating GLP-1 levels during oral glucose tolerance test (OGTT) among subjects with normal glucose tolerance (NGT) and T2DM.

Methods: A total of 120 subjects consisting of NGT (n=58) and T2DM (n=62) had their plasma total GLP-1 concentrations measured at 0, 30 and 120 min following a 75 g OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of insulin sensitivity (HOMA-IS) and triglyceride glucose (TyG) index were calculated. All the above parameters were subsequently assessed in T2DM subjects of <1 year vs ≥ 1 year of disease duration to elicit if there are any subtle differences in their respective GLP-1 responses.

Results: Total GLP-1 levels at fasting (fGLP-1) and 30 min (GLP-1_30min) were significantly higher in T2DM than NGT (fGLP-1 27.18±11.56 pmol/L vs. 16.24 ±7.79 pmol/L, p<0.005; GLP-1_30min 50.22±18.03 pmol/L vs. 31.44 ±22.59 pmol/L, p<0.001; respectively). The GLP-1 levels were positively correlated with HOMA-IR and TyG index but negatively correlated with HOMA-IS. T2DM subjects with disease duration < 1 year had higher GLP-1 response than those with disease duration ≥1 year (GLP-1_30min 55.33±18.09 pmol/L vs. 46.02±17.12 pmol/L, p<0.05).

Conclusion: The augmented GLP-1 levels in T2DM represents an adaptive compensatory response to increasing insulin resistance, a phenomenon we aptly refer to as “hypergliptinemia”. However, this phenomenon is transient as the incretin response started to diminish after one year of diagnosis in keeping with the progressive nature of T2DM.