Glycemic Response to Oral Dexamethasone Predicts Incident Prediabetes in Normoglycemic Subjects With Parental Diabetes

Abstract

Background Prediabetes, an often unrecognized precursor of type 2 diabetes (T2DM), is associated with cardiometabolic complications. Here, we investigated the utility of dexamethasone challenge in predicting incident prediabetes among normoglycemic subjects with parental T2DM enrolled in the prospective Pathobiology of Prediabetes in a Biracial Cohort study. Design and Methods After documenting normoglycemic status with an oral glucose tolerance test (OGTT), participants ingested dexamethasone (2 mg) at 10:00 pm, and fasting plasma glucose (FPG-Dex) and cortisol were measured at 8:00 am the next day. Subjects were followed quarterly for 5 years, the primary outcome being incident prediabetes. Serial assessments included body composition, blood chemistry, OGTT, insulin sensitivity, and secretion. Results We analyzed data from 190 participants (107 Black, 83 white; mean age 44.7 ± 10.0 years; body mass index [BMI] 29.8 ± 6.8 kg/m²; fasting plasma glucose [FPG] 90.9 ± 5.7 mg/dL). Following dexamethasone ingestion, plasma cortisol was < 5 µg/dL; FPG-Dex levels displayed marked variability (81-145 mg/dL) as did delta FPG (–7 to +48 mg/dL). During 5 years of follow-up, 58 of 190 subjects (30.5%) progressed to prediabetes. FPG-Dex (116.8 ± 10.9 vs 106.9 ± 10.8 mg/dL, P < 0.0001) and delta FPG (23.4 ± 10.1 vs 17.0 ± 10.2 mg/dL, P < 0.0001) were higher in progressors than nonprogressors. FPG-Dex (P = 0.007) was an independent predictor of incident prediabetes in a multivariate model that included age, race, gender, BMI, waist circumference, FPG, insulin sensitivity, and secretion. In further analyses, an FPG-Dex level ≥ 107 mg/dL predicted incident prediabetes with 88% sensitivity and 49% specificity. Conclusions The glycemic response to dexamethasone significantly predicted incident prediabetes among offspring of parents with T2DM, and may be a tool for uncovering latent risk of dysglycemia.