Parental History of Type 2 Diabetes Abrogates Ethnic Disparities in Key Glucoregulatory Indices.

Abstract

There are ethnic differences in glucoregulation and prevalence of type 2 diabetes, but studies on the role of genetics in modifying ethnic effects in normoglycemic African-Americans and Caucasians are limited. Therefore, we investigated glucoregulation in normoglycemic African-Americans and Caucasians with or without parental diabetes. Fifty subjects with parental diabetes (from the Pathobiology of Prediabetes in a Biracial Cohort Study) and 50 subjects without parental diabetes were matched in age, sex, ethnicity, and body mass index (BMI). Subjects underwent a 75-g oral glucose tolerance test (OGTT), physical examination, anthropometry, biochemistries, indirect calorimetry and assessment of body composition, insulin sensitivity by euglycemic clamp (Si-clamp), and β-cell function by Disposition index. The mean age was 40.5 ± 11.6 years, BMI 28.7 ± 5.9 kg/m2, fasting plasma glucose 90.2 ± 5.9 mg/dL, and 2-hour postglucose 120.0 ± 26.8 mg/dL. Offspring with parental diabetes showed higher glycemic excursion during OGTT-area under the curve-glucose (16,005.6 ± 2324.7 vs 14,973.8 ± 1819.9, P < 0.005), lower Si-clamp (0.132 ± 0.068 vs 0.162 ± 0.081 µmol/kg fat-free mass/min/pmol/L, P < 0.05), and lower Disposition index (8.74 ± 5.72 vs 11.83 ± 7.49, P < 0.05). Compared with lean subjects without parental diabetes, β cell function was lower by ∼30% in lean subjects with parental diabetes, ∼40% in obese subjects without parental diabetes, and ∼50% in obese individuals with parental diabetes (P < 0.0001). African-Americans without parental diabetes had ∼40% lower insulin sensitivity (P < 0.001), twofold higher acute insulin secretion (P < 0.001), but ∼30% lower Disposition index (P < 0.01) compared with Caucasians without parental diabetes. Remarkably, there were no significant differences by ethnicity in these glucoregulatory measures among subjects with parental diabetes. Offspring with parental diabetes harbor substantial impairments in glucoregulation compared with individuals without parental diabetes. Ethnic disparities in glucoregulation were abrogated by parental diabetes.