Metabolic inflexibility in substrate use is present in African-American but not Caucasian healthy, premenopausal, nondiabetic women.

CONTEXT: There is an increased prevalence of obesity and insulin resistance in African-American compared with Caucasian females. Metabolic inflexibility (MI) is the inability to switch the use of lipids and carbohydrates in the peripheral tissue (i.e. muscle) based upon substrate availability. OBJECTIVE: We examined whether MI exists in African-American females. MAIN OUTCOME MEASURES AND DESIGN: We measured substrate use differences during eucaloric, macronutrient-manipulated diets [high fat (50% fat, 35% carbohydrate, 15% protein) vs. low fat (30% fat, 55% carbohydrate, 15% protein)] between Caucasian and African-American women. We also compared differences in substrate use in response to insulin infusion during two-step pancreatic-euglycemic clamps and epinephrine infusion during lipolysis studies. In each study, similar groups of Caucasian and African-American women were compared. RESULTS: Caucasians had significantly higher fat oxidation (FO) (P = 0.01) and lower carbohydrate oxidation (P < 0.01) during the high-fat vs. low-fat diet, whereas no significant differences were observed in African-Americans. The African-American women also failed to significantly suppress FO during the second step of the pancreatic-euglycemic clamp despite a doubling of their fasting plasma insulin and failed to increase their FO or decrease their carbohydrate oxidation in response to epinephrine infusion as much as Caucasian women did. The response of free fatty acid turnover rates to insulin and epinephrine stimulation was similar between races. CONCLUSION: The impaired substrate use observed in African-American women during these three studies demonstrates the existence of MI and may contribute to their greater prevalence of obesity and insulin resistance.

Independent association of insulin resistance with larger amounts of intermuscular adipose tissue and a greater acute insulin response to glucose in African American than in white nondiabetic women.

BACKGROUND: African Americans (AAs) have a higher prevalence of obesity and type 2 diabetes than do whites. Higher insulin resistance and hyperinsulinemia have been reported in adult AAs than in whites. Differences in adipose tissue and its distribution may account for these findings. OBJECTIVE: The objective was to ascertain whether differences between AA and white women in adipose tissue (AT) and skeletal muscle (SM) volumes account for ethnic differences in insulin resistance. DESIGN: We used whole-body magnetic resonance imaging to measure AT and SM volumes and used the intravenous-glucose-tolerance test to measure insulin resistance. RESULTS: AAs (n = 32) were 29-42% more insulin resistant than were whites (n = 28) after adjustment for weight and height or any AT volumes (P < 0.05). After adjustment for SM volume, the difference decreased to 19% and became nonsignificant. AAs had a 163% greater acute insulin response to glucose than did whites; this difference was significant even after adjustment for insulin sensivitity index, weight, height, and any magnetic resonance imaging measures. With respect to regional AT volumes, an association independent of race, weight, height, and SM volume was found only between increased intermuscular AT and lower insulin sensitivity index. CONCLUSIONS: Premenopausal AA women had significantly higher insulin resistance and acute insulin response to glucose than did their white counterparts. Whereas the difference in insulin resistance was partially accounted for by a greater SM volume in the AAs than in the whites, the difference in the acute insulin response to glucose was independent of any AT and SM measures and was disproportionately larger than expected according to the difference in insulin resistance. In addition, whole-body intermuscular AT was an important independent correlate of insulin resistance.

Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women.

OBJECTIVE: Adiponectin influences insulin sensitivity (S(I)) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's SI. RESEARCH METHODS AND PROCEDURES: We measured changes in adiponectin, insulin, glucose, and leptin in response to high-fat (HF) and low-fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori SI. RESULTS: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 +/- 9.8; LF, 20.8 +/- 6.6; obese, HF 10.0 +/- 3.3; LF, 9.5 +/- 2.3 ng/mL; mean +/- SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin-sensitive subjects had significantly higher adiponectin during HF than did the insulin-resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects' baseline SI. DISCUSSION: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured SI in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves SI in an already obese group.