2152-LB: Prediabetes Phenotypes Defined by Glucose-Stimulated Insulin Response Using Hyperglycemic Clamp in Healthy Young People

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Introduction and Objective: Prediabetes, often classified by static glucose measures, limits identification of impaired beta-cell function beyond response to prevailing insulin sensitivity. We implemented hyperglycemic clamps (HG) to classify prediabetes phenotypes based on stimulated insulin response. Methods: We screened healthy individuals (n=2500, 18-45 yrs, BMI 18.5-25 kg/m2) and recruited (37 normal glycemia, NG; 63 prediabetes, preD) participants based on ADA HbA1c cutoff (5.7). Whole blood was collected at 17 time points during HG clamp. Glucose, insulin, C-peptide, HOMAIR and HOMA B% were measured. Statistical analysis included Wilcoxon test to compare groups and K-means clustering to identify subtypes of prediabetes. Differences between preD clusters at baseline, 1st (10 min) and 2nd phase (120 min) insulin secretion were assessed. Results: Compared to NG, preD had higher glucose (p=0.028) at 120 min, lower C-peptide [baseline (p=0.048), 1st phase (p=0.024), 2nd phase (p=0.006)] and lower HOMA-B at baseline and 2nd phase. K-means clustering using C-peptide and HOMA-B identified two clusters: high insulin cluster (preD1), low insulin cluster (preD2) (Table). Conclusion: HG clamps in prediabetes individuals suggest heterogeneity and majority have lower 2nd phase glucose-stimulated insulin response compared to NG individuals, indicating beta-cell dysfunction as a major contributor to prediabetes in Indians. Disclosure V. Natarajan: None. B. Attunuru: None. D. Shankar: None. P.R. Somvanshi: None. V. Nayanatara: None. S. Pinninti: None. S. Kulkarni: None. K.R. Choudari: None. L. Staimez: None. A.C. Powers: None. K. Narayan: None. A. Kurpad: None. M. Sasikala: None. Funding DBT Wellcome Trust India Alliance (IA/CRC/23/1/600505)

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