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

Context: 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.

Design: 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.

Results: 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.

Conclusion: Offspring with parental diabetes harbor substantial impairments in glucoregulation compared with individuals without parental diabetes. Ethnic disparities in glucoregulation were abrogated by parental diabetes.