Increased Gluconeogenesis Is Not an Early Feature of Whole-Body Insulin Resistance in Black Women—The Federal Women Study

Abstract

In contrast to white women, fasting hyperglycemia is not an early diabetes risk marker in black women. The etiology of this racial difference in risk is unknown but could be related to differences in rates of gluconeogenesis and hepatic fat in black women. Using stable isotope tracers [2H2O], [6,62H2]glucose, and ([2H5]glycerol), we partitioned basal glucose production into its two components (gluconeogenesis and glycogenolysis) and measured basal whole body lipolysis. Whole body (SI), hepatic (HIS) and adipose tissue insulin sensitivity were calculated in two groups of federally employed pre-menopausal women, without diabetes: 24 black and 19 white; age 37±6 (mean±SD), range 25-50y; BMI 33±6, range 24.9-45.2 kg/m2. Hepatic and visceral fat were measured by proton MRS. The prevalence of prediabetes (17% vs. 26%), age and BMI were similar in blacks and whites, all P>0.4). Black women had less fasting hyperglycemia (4% vs. 22%, P=0.1), lower visceral and hepatic fat (P<0.01) but similar SI, adipose tissue insulin sensitivity and whole body lipolysis (all P>0.5). Basal glucose, insulin and FFA concentrations were similar in both groups (P>0.05). Blacks had lower glucose production (2.52±0.34 vs. 2.75±0.28 mg·kglbm-1·min-1, P<0.05), fractional gluconeogenesis (57.6±10.6 vs. 66.3±11.4%, P=0.02), and absolute gluconeogenesis (1.44±0.28 vs. 1.77±0.31 mg·kglbm-1·min-1, P<0.01). HIS correlated with SI and hepatic fat (both r=0.5, P<0.01) and the relationship did not differ by race (P>0.05). However, at the same SI blacks had higher HIS (intercepts P<0.01). In summary, black women had relatively preserved HIS and lower hepatic fat, while white women had higher gluconeogenesis and hepatic fat associated with fasting hyperglycemia. Fasting glucose may be a poor early diabetes marker in black women because gluconeogenesis was low despite whole-body insulin resistance. Disclosure S.T. Chung: None. M.W. Haymond: Advisory Panel; Self; Zealand Pharma A/S. Other Relationship; Self; Xeris Pharmaceuticals, Inc.. A. Onuzuruike: None. L. Mabundo: None. H. Garraffo: None. P.J. Walter: None. A.B. Courville: None. A.M. Gharib: None. S. Chacko: None. A.E. Sumner: None.