Effect of a 1-week, eucaloric, moderately high-fat diet on peripheral insulin sensitivity in healthy premenopausal women.

OBJECTIVES: To determine whether a weight-maintaining, moderate (50%) high-fat diet is deleterious to insulin sensitivity in healthy premenopausal women. DESIGN/SETTING/PARTICIPANTS: 23 African-American and non-Hispanic white, healthy, overweight, and obese premenopausal women recruited in New York City, USA, fed either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a randomized crossover design. MAIN OUTCOME MEASURES: Peripheral insulin sensitivity and metabolic flexibility during a euglycemic hyperinsulinemic (80 mU/m(2)/min) clamp measured during the follicular phase of the menstrual cycle, at the end of each diet period. RESULTS: Peripheral insulin sensitivity (mg kg/fat-free mass/min (µU/mL)×10(-1)) was not decreased after the high-fat diet vs the low-fat diet (0.09±0.01 vs 0.08±0.01, p=0.09, respectively) in the combined group of African-American and white women, with no significant diet by race interaction (p=0.6). Metabolic flexibility (change in substrate utilization, ΔNPRQ, in response to insulin during the clamp) was similarly unaltered by the diet (0.12±0.01 vs 0.11, p=0.48, for the high-fat diet vs the low-fat diet, respectively) in the combined group of women, with no significant diet by race interaction (p=0.9). African-American women had a lower insulin clearance compared with the white women, regardless of the diet (p<0.05). CONCLUSIONS: We conclude that a short term (1 week), moderate (50%), eucaloric high-fat diet does not lower peripheral insulin sensitivity in healthy, overweight and obese premenopausal women.

Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P < 0.05). In addition, orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P < 0.05), total fat mass loss (-4.65 kg vs. -3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo-treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes.

OBJECTIVE: To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate [GDR]), fasting glucose, and free fatty acids (FFAs) and concomitant changes in weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured GDR, fasting glucose, and FFAs during a euglycemic clamp and adipose tissue mass and distribution, organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and after 1 year of diet and exercise aimed at weight loss. RESULTS: Weight and fasting glucose decreased significantly (P < 0.0001) and significantly more in men than in women (-12 vs. -8% and -16 vs. -7%, respectively; P < 0.05), while FFAs during hyperinsulinemia decreased and GDR increased significantly (P < 0.00001) and similarly in both sexes (-53 vs. -41% and 63 vs. 43%; P = NS). Men achieved a more favorable fat distribution by losing more from upper compared with lower and from deeper compared with superficial adipose tissue depots (P < 0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR but not in fasting glucose or fasting FFAs; however, decreases in FFAs during hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the only regional fat measure whose change contributed independently to changes in metabolic variables. CONCLUSIONS: Patients with type 2 diabetes undergoing a 1-year lifestyle intervention had significant improvements in GDR, fasting glucose, FFAs and adipose tissue distribution. However, changes in overall weight (adipose tissue mass) and hepatic fat were the most important determinants of metabolic improvements.

Higher post-absorptive skeletal muscle LPL activity in African American vs. non-Hispanic White pre-menopausal women.

OBJECTIVE: Higher post-absorptive post-heparin plasma lipoprotein lipase (LPL) activity has been reported in African Americans as compared to non-Hispanic whites but differences in tissue-specific LPL activity are unclear. METHODS AND PROCEDURES: Post-absorptive skeletal muscle (SM)-LPL (vastus lateralis ) and subcutaneous abdominal adipose tissue (AT)-LPL activity was measured in overweight, sedentary African American females (n = 11) as well as in their non-Hispanic white counterparts (n = 6) during a period of controlled low fat (30%) diet (for 10 days) combined with physical activity (for days 8-10). Post-absorptive substrate utilization was measured on day 10; fasting blood levels and SM and AT biopsies were obtained on day 11. RESULTS: African Americans had significantly greater post-absorptive SM-LPL activity (P = 0.04) when compared to non-Hispanic whites. There were no significant differences in post-absorptive AT-LPL activity, free fatty acids, and systemic fat oxidation or respiratory quotient between African American and white non-Hispanic women in this study (P > 0.2 for all). DISCUSSION: During a controlled low fat (30%) diet post-absorptive vastus lateralis SM-LPL activity is higher in sedentary pre-menopausal African American as compared to non-Hispanic white women.

Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women.

BACKGROUND: Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART). OBJECTIVE: The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women. DESIGN: Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (S(I)) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n=17) and in obese healthy controls (n=32). RESULTS: The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P<0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with S(I) (P<0.001 for the regression's slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with S(I) did not differ significantly between groups. For both groups combined, the best model predicting a low S(I) included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r(2)=0.44, P=0.0003). CONCLUSION: In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance.

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.

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.