History of gestational diabetes leads to distinct metabolic alterations in nondiabetic African-American women with a parental history of type 2 diabetes.

OBJECTIVE: Gestational diabetes mellitus (GDM) and positive parental history of type 2 diabetes are predictors of the future development of type 2 diabetes in several populations. However, the relative importance of parental history of diabetes and/or history of GDM as risk factors for the pathogenesis of diabetes in African-Americans remains unknown. Thus, the objectives of the present study were 1) to characterize the glucose homeostatic regulations and 2) to examine the contribution of parental history of type 2 diabetes to the potential metabolic alterations found in nondiabetic African-American women with a history of GDM (HGDM). RESEARCH DESIGN AND METHODS: We evaluated beta-cell secretion, insulin sensitivity (SI), and glucose-dependent glucose disposal (SG) in 15 glucose-tolerant African-American women with a parental history of type 2 diabetes and prior GDM (HGDM) and 35 women with a parental history of type 2 diabetes but without prior GDM (NHGDM). Fifteen healthy nonobese nondiabetic subjects without a family history of diabetes served as control subjects. Body composition was determined by bioelectrical impedance analyzer, and body fat distribution pattern was determined by waist-to-hip ratio (WHR). Insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test was performed in each subject. SI and SG were determined by the minimal model method.
RESULTS: The mean age, BMI, percent body fat content, and lean body mass were not different between the subgroups of relatives with and without a history of GDM, but were greater than those of the healthy control subjects. Mean fasting and postchallenge serum glucose levels were slightly but significantly greater in the HGDM versus NHGDM subjects and the healthy control subjects. However, the 2-h glucose levels were greater in the relatives with and without GDM when compared with the healthy control subjects. In contrast, mean postprandial serum insulin responses were significantly lower between t = 30 and 120 min in the HGDM versus NHGDM groups and the healthy control subjects. The mean serum insulin levels were not different in the NHGDM subjects and healthy control subjects. During the FSIGT test, acute first-phase insulin release (t = 0-5 min) was significantly lower in the HGDM versus NHGDM groups and healthy control subjects. Mean SI was significantly (P < 0.05) lower in the HGDM versus NHGDM subjects and healthy control subjects (1.87 +/- 0.47 vs. 2.87 +/- 0.35 and 3.09 +/- 0.27 x 10(-4).min-1.[microU/ml]-1, respectively). SG was significantly lower in HGDM than NHGDM subjects and healthy control subjects (2.11 +/- 0.15 vs. 3.25 +/- 0.50 and 2.77 +/- 0.22 x 10(-2).min-1, respectively). Mean glucose effectiveness at zero insulin concentrations (GEZI) was significantly lower in the HGDM subjects when compared with the NHGDM and healthy control subjects.
CONCLUSIONS: The present study demonstrates that in African-American women with a parental history of type 2 diabetes and GDM, defects in early-phase beta-cell secretion, as well as a decreased SI, SG, and GEZI, persist when compared with those without GDM. We suggest that African-American women with a positive history of GDM have additional genetic defects that perhaps differ from that conferred by a parental history of diabetes alone. Alternatively, the metabolic and hormonal milieu during GDM may be associated with permanent alterations in beta-cell function, SI, and glucose effectiveness in African-American women. These defects could play a significant role in the development of GDM, and perhaps in the subsequent development of type 2 diabetes, in African-American women.