Glucose Metabolism and Diet Predict Changes in Adiposity and Fat Distribution in Weight‐reduced Women

Among obesity‐prone individuals, metabolic state may interact with diet in determining body composition. We tested the hypotheses that, among 103 weight‐reduced women over 1 year, (i) insulin sensitivity would be positively associated with change in %fat; (ii) this association would be modulated by dietary glycemic load (GL); and (iii) changes in fat distribution would be related to indexes of glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and postchallenge insulin and glucose, and glucose tolerance were assessed during intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution were examined using dual‐energy X‐ray absorptiometry and computed tomography. Dietary GL was assessed on 67 women using food records. On average, women showed a +5.3 ± 3.0% change in %fat over 1 year, with the magnitude of this change being greater in relatively insulin sensitive women (+6.0 ± 0.4%, mean ± s.e.m.) than in relatively insulin resistant women (+4.4 ± 0.4 kg; P < 0.05). Women who were relatively insulin sensitive and who consumed a higher GL diet showed a +6.8 ± 0.7% change in %fat, which was greater than those who were less insulin sensitive, regardless of diet (P < 0.05), but did not differ from women who were relatively insulin sensitive and who consumed a lower GL diet (P = 0.105). Changes in intra‐abdominal and deep subcutaneous abdominal fat were inversely associated with the postchallenge decline in serum glucose. In conclusion, greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet. The potential association between indexes of glucose disposal and changes in fat distribution warrants further study.     

The Insulin Tolerance Test in Morbidly Obese Patients Undergoing Bariatric Surgery

Objective: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients. Research Methods and Procedures: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 ± 8.8 kg/m²) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux‐en‐Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated. Results: A reduction of 68 ± 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin‐sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups. Discussion: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Post‐Exercise Substrate Utilization after a High Glucose vs. High Fructose Meal During Negative Energy Balance in the Obese

Objective: To assess the effects of negative energy balance on the metabolic response of a meal containing either glucose or fructose as the primary source of carbohydrate after exercise in obese individuals in energy balance, or negative energy balance. Research Methods and Procedures: Fourteen adults with mean body mass index (BMI) 30.3 ± 1 kg/m², age 26 ± 2 years, and weight 93.5 ± 5.4 kg, adhered to an energy‐balanced (EB) or a negative energy‐balanced (NEB) diet for 6 days. On Day 7, subjects exercised at 70% VO_2peak for 40 minutes then consumed either high glucose (50 g of glucose, HG) or high fructose (50 g of fructose, HF) liquid meal. Substrate utilization was measured by indirect calorimetry for 3 hours. Blood samples were collected before exercise and 0, 30, 60, 120, and 180 minutes after consuming the meal. Results: The HG produced 15.9% greater glycemic (p < 0.05) and 30.9% larger insulinemic (p < 0.05) responses than the HF under both EB and NEB conditions. After the NEB diet, carbohydrate and fat oxidation did not differ for HG and HF. In contrast, carbohydrate oxidation increased 31%, and fat oxidation decreased 39% with HF compared with HG after the EB diet. Thus, HF and HG consumed after exercise produced marked differences in macronutrient oxidation when obese subjects followed an EB diet, but no difference when adhering to a NEB diet. Discussion: The data suggest that the use of fructose in supplements/meals may provide no additional benefit in terms of substrate utilization during a weight loss program involving diet and exercise.     

Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin −0.7 ± 0.7%, p ≤ 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 ± 14.5 μmol glucose/min/kg free fat mass, p < 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p ≤ 0.05) with RSG (2.1 ± 2.0 kg and 1.4 ± 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 ± 28.7 cm², p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (−6.7 ± 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.     

Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity. Results from a randomized controlled trial with 5-year follow-up

C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To study the effects of lifestyle on CRP in a high-risk population we conducted a randomized controlled trial on 200 obese subjects (BMI > 27 kg m^?2) with impaired glucose tolerance recruited from primary care settings. They were randomized to either a 1-month stay at a wellness centre focusing on diet, exercise and stress management (intervention group) or 30–60 min of oral and written information on lifestyle intervention (control group). A significant reduction of CRP was observed after 1 month and 1 year in the intervention group. They reduced their CRP levels more than the control group 1 year after intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in obese individuals with impaired glucose tolerance for up to 1 year. Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity.     

The Effect of Dietary Glycemic Index on Weight Maintenance in Overweight Subjects: A Pilot Study

Evidence suggests that a low‐glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight‐loss maintenance. It consisted of a weight‐loss phase and a 4‐month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2–7.1) % body weight, subjects were randomized to a high‐glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 ± 9.4; LGI group: 49.7 ± 5.7, P < 0.001) and glycemic load (HGI group: 136.8 ± 56.3; LGI group: 89.7 ± 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 ± 1.9 kg; LGI group: −0.7 ± 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.     

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats

Objective: The effects of a very low‐carbohydrate (VLC), high‐fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high‐carbohydrate (HC), low‐fat (LF) regimen in dietary obese rats. Research Methods and Procedures: Male Sprague‐Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post‐load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC‐HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one‐half (HC) were pair‐fed an HC‐LF diet (Weeks 9 to 14 at 60% carbohydrate). Results: Energy intakes of pair‐fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. Discussion: When energy intake was matched, the VLC‐HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC‐LF diet.     

Response of animals to dietary gramine. II. effects of feeding high‐gramine yellow lupin seeds on reproductive performance of rats and on selected hematological and biochemical parameters in offspring

Two groups of 26 male and 26 female rats at the initial age 30 ± 2 days were fed during 31 weeks on diets containing 20 percent of yellow lupin seeds having low (LG) or high (HG) gramine content. The animals were mated twice within nutritional groups, 1 male: 1 female, and their main reproductive parameters were recorded. In both reproductive cycles body weight of females at mating, after parturition and after 21‐days lactation was lower in HG than in LG group. Fertility rate and body weight of neonates were not affected by the diet while number of neonates per litter tended to be lower by 0.7 and 0.8 pups in HG than in LG group. Body weight of weaners was also substantially smaller in dams fed on HG than LG diet. Relative weight of spleen but not of liver, kidney and heart was significantly greater in HG females. Four weeks old males and females issued from the first litters born to LG and HG animals (ten males and ten females per treatment) were fed individually on respective diets during 3 weeks. Feed intake and growth rate did not differ between the treatments. In males relative weight of liver and testicles was greater, while hematocrit and red blood count were lower in HG than in LG group. In females organ weights did not differ. Activity of liver enzymes determined in males was not affected by the diet. It may be concluded that high‐gramine lupin affects negatively lactational performance, probably via lower feed intake, but it does not induce apparent teratogenic effects in the progeny.     

Characterization and heritability of obesity and associated risk factors in vervet monkeys

Objective: The objective was to determine the prevalence and heritability of obesity and risk factors associated with metabolic syndrome (MS) in a pedigreed colony of vervet monkeys. Design: A cross‐sectional study of plasma lipid and lipoprotein concentrations, glycemic indices, and morphometric measures with heritability calculated from pedigree analysis. A selected population of females was additionally assessed for insulin sensitivity and glucose tolerance. Subjects: All mature male (n = 98), pregnant (n = 40) and non‐pregnant female (n = 157) vervet monkeys were included in the study. Seven non‐pregnant females were selected on the basis of high or average glycated hemoglobin (GHb) for further characterization of carbohydrate metabolism. Measurements: Morphometric measurements included body weight, length, waist circumference, and calculated BMI. Plasma lipids [total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C)] and glycemic measures (fasting blood glucose, insulin, and GHb) were measured. A homeostasis model assessment index was further reported. Glucose tolerance testing and hyperinsulinemic‐euglycemic clamps were performed on 7 selected females. Conclusion: Vervet monkeys demonstrate obesity, insulin resistance, and associated changes in plasma lipids even while consuming a low‐fat (chow) diet. Furthermore, these parameters are heritable. Females are at particular risk for central obesity and an unfavorable lipid profile (higher TG, TC, and no estrogen‐related increase in HDL‐C). Selection of females by elevated GHb indicated impaired glucose tolerance and was associated with central obesity. This colony provides a unique opportunity to study the development of obesity‐related disorders, including both genetic and environmental influences, across all life stages.     

Modest Lifestyle Intervention and Glucose Tolerance in Obese African Americans

Objective: Previous studies have demonstrated the benefit of short‐term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short‐term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. Research Methods and Procedures: An intervention group (n = 45; 47 ± 1 year [mean ± SE]), 105 ± 4 kg; body mass index: 39 ± 1 kg/m²) received an energy‐restricted diet (943 ± 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (?125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C‐peptide during an oral glucose tolerance test were measured at baseline, 1‐week, and 4‐month intervals. A control group (n = 24; 48 ± 1 year; 110 ± 5 kg; body mass index: 41 ± 2 kg/m²) underwent these measurements at 4‐month intervals. Results: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1‐week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: ?4.6 ± 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: ?103 ± 44 mM · min; p < 0.05 vs. control). Discussion: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.     

Evaluation ofin vivo insulin action and glucose metabolism in milk-fed rats

Milk diet has long been recommended in the management of gastrointestinal pathologies. Since milk feeding represents a high fat-low carbohydrate diet and it is acknowledged that insulin resistance is one of the consequences of high fat feeding, it is important to know whether or not chronic milk feeding leads to an impairment of the insulin-mediated glucose metabolism. To examine this question, adult female rats were given raw cow's milk (50% of total calories as lipids) for 18 days. They were compared to rats raised in parallel and fed the standard laboratory diet (15% of total calories as lipids). At the end of the 18 day period, body weight, daily caloric intake, basal plasma glucose and insulin levels in the milk-fed rats were similar to those in the control rats.In vivo insulin action was assessed with the euglycemichyperinsulinemic clamp technique in anesthetized animals. These studies were coupled with the 2-deoxyglucose technique allowing a measurement of glucose utilization by individual tissues. In the milk fed rats: 1) the basal rate of endogenous glucose production was significantly (p<0.01) reduced (by 20%); 2) their hepatic glucose production was however normally suppressed by hyperinsulinemia; 3) their basal glucose utilization rate was significantly (p<0.01) reduced (by 20%); 4) their glucose utilization rate by the whole-body mass or by individual tissues was normally increased by hyperinsulinemia. These results indicate that insulin action in adult rats is not grossly altered after chronic milk-feeding, at least under the present experimental conditions.     

Beta-cell dysfunctions and insulin resistance in subjects with increased risk for type 2 diabetes mellitus

The aim of this study was to test if a beta-cell defect is associated to deterioration of glucose tolerance early during the natural history of the type 2 diabetes mellitus . In 41 overweight women, with macrosomic infants in their antecedent deliveries, measures of insulin response and insulin sensitivity were derived from a short (45 min) iv glucose test. The early (EIR) and the late (LIR) phase insulin responses and the insulin sensitivity index (Si) were calculated. According the response to 75 g oral glucose test the subjects were divided into two groups: Imparired glucose tolerance (IGT;n = 12), and normal glucose tolerance (NGT; n = 29). EIR was reduced in IGT group (14.9 ± 3.6 vs 37.0 ± 4.0; p< 0.002). Glucose tolerance during oral glucose tolerance test (OGTT), correlated inversly to EIR (r=-0.45; n=41; p< 0.01). A strong correlation of EIR to LIR (r=0.88; n = 41; p< 0.001) but no correlation between glucose tolerance and Si was found.     

S 23521 Decreases Food Intake and Body Weight Gain in Diet‐Induced Obese Rats

Objective: To investigate the effect of S 23521, a new glucagon‐like peptide‐1‐(7‐36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis. Research Methods and Procedures: Lean and diet‐induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 μg/kg) or subcutaneously (100 μg/kg) for 14 and 20 days, respectively. Because the low‐dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end‐points. Results: Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle‐treated counterparts (3401 ± 65 vs. 3898 ± 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein‐1, uncoupling protein‐3, leptin, resistin, and peroxisome proliferator‐activated receptor (PPAR)‐γ were observed. Discussion: S 23521 is an effective glucagon‐like peptide‐1‐(7‐36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet‐induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.     

Randomized Control Trial to Improve Adiposity and Insulin Resistance in Overweight Latino Adolescents

Few randomized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth. The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity, adiposity, and other type 2 diabetes risk factors in overweight Latino adolescents. In a 16‐week randomized trial, 54 overweight Latino adolescents (15.5 ± 1.0 years) were randomly assigned to: (i) Control (C; n = 16), (ii) Nutrition (N; n = 21), or (iii) Nutrition + Strength training (N+ST; n = 17). The N group received modified carbohydrate nutrition classes (once per week), while the N+ST received the same nutrition classes plus strength training (twice per week). The following were measured at pre‐ and postintervention: strength by 1‐repetition maximum, dietary intake by 3‐day records, body composition by dual‐energy X‐ray absorptiometry, glucose/insulin indices by oral glucose tolerance test (OGTT) and intravenous glucose tolerance test with minimal modeling. Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons. A significant overall intervention effect was found for improvement in bench press (P < 0.001) and reductions in energy (P = 0.05), carbohydrate (P = 0.04) and fat intake (P = 0.03). There were no significant intervention effects on insulin sensitivity, body composition, or most glucose/insulin indices with the exception of glucose incremental area under the curve (IAUC) (P = 0.05), which decreased in the N and N+ST group by 18 and 6.3% compared to a 32% increase in the C group. In conclusion, this intense, culturally tailored intervention resulted in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose.     

No Decrease in Free IGF‐I with Increasing Insulin in Obesity‐Related Insulin Resistance

Objective: Different facts suggest that the insulin growth factor (IGF)/ insulin growth factor‐binding protein (IGFBP) system may be regulated by factors other than growth hormone. It has been proposed that, in healthy subjects, free IGF‐I plays a role in glucose metabolism. The role of free IGF‐I in glucose homeostasis in insulin resistance is poorly understood. This study was undertaken to evaluate the effects of acute changes in plasma glucose and insulin levels on free IGF‐I and IGFBP‐1 in obese and non‐obese subjects. Research Methods and Procedures: Nineteen lean and 24 obese subjects were investigated. A frequently sampled intravenous glucose tolerance test was performed. Free IGF‐I and IGFBP‐1 were determined at 0, 19, 22, 50, 100, and 180 minutes. Results: Basal free IGF‐I levels tended to be higher and IGFBP‐1 lower in obese than in lean subjects. IGFBP‐1 levels inversely correlated with basal insulin concentration. To determine the effects of insulin on the availability of free IGF‐I and IGFBP‐1, changes in their plasma concentrations were measured during a frequently sampled intravenous glucose tolerance test. After insulin administration, a significant suppression of free IGF‐I at 22% was observed in lean subjects. In contrast, plasma‐free IGF‐I levels remained essentially unchanged in the obese group. The differences between both groups were statistically significant at 100 minutes (p < 0.01) and 180 minutes (p < 0.05). Serum IGFBP‐1 was suppressed to a similar extent in both groups. Discussion: These data suggest that the concentrations of free IGF‐I and IGFBP‐1 are differentially regulated by obesity. Obesity‐related insulin resistance leads to unsuppressed free IGF‐I levels.     

Effects of Exercise on Metabolic Risk Variables in Overweight Postmenopausal Women: A Randomized Clinical Trial

Objective: This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women. Research Methods and Procedures: Sedentary women (n = 173) who were overweight or obese (BMI ≥ 25 kg/m² or ≥24 kg/m² with ≥33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (≥45 minutes of moderate‐intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow‐up were calculated and compared across groups. Results: Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12‐month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass. Discussion: Regular moderate‐intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.     

Chronological approach of diet-induced alterations in muscle mitochondrial functions in rats

Objective: Mitochondrial dysfunction might predispose individuals to develop insulin resistance. Our objective was to determine whether mitochondrial dysfunction or insulin resistance was the primary event during high‐fat (HF) diet. Research Methods and Procedures: Rats were fed an HF diet for 0, 3, 6, 9, 14, 20, or 40 days and compared with control. Soleus and tibialis muscle mitochondrial activity were assessed using permeabilized fiber technique. Insulin [area under the curve for insulin (AUC_I)] and glucose [area under the curve for glucose (AUC_G)] responses to intraperitoneal glucose tolerance test as well as fasting plasma non‐esterified fatty acids (NEFAs), triglyceride, and glycerol concentrations were determined. Results: AUC_I and AUC_G were altered from Day 6 (p < 0.01 vs. Day 0). In soleus, oxidative phosphorylation (OXPHOS) activity was transiently enhanced by 26% after 14 days of HF diet (p < 0.05 vs. Day 0) conjointly with 62% increase in NEFA concentration (p < 0.05 vs. Day 0). This was associated with normalized AUC_G at Day 14 and with a decline of plasma NEFA concentration together with stabilization of intra‐abdominal adiposity at Day 20. Prolongation of HF diet again caused an increase in plasma NEFA concentration, intra‐abdominal adiposity, AUC_I, and AUC_G. At Day 40, significant decrease in OXPHOS activity was observed in soleus. Discussion: Mitochondria first adapt to overfeeding in oxidative muscle limiting excess fat deposition. This potentially contributes to maintain glucose homeostasis. Persistent overfeeding causes insulin resistance and results in a slow decline in oxidative muscle OXPHOS activity. This shows that the involvement of mitochondria in the predisposition to insulin resistance is mainly due to an inability to face prolonged excess fat delivery.     

Isocaloric intake of a high‐fat diet promotes insulin resistance and inflammation in Wistar rats

The aim of this study was to investigate the effect of isocaloric intake from a high‐fat diet (HFD) on insulin resistance and inflammation in rats. Male Wistar rats were fed on an HFD (n = 12) or control diet (n = 12) for 12 weeks. Subsequently, all animals were euthanized, and blood glucose, insulin, free fatty acids, C‐reactive protein, lipid profile, cytokines and hepatic‐enzyme activity were determined. Carcass chemical composition was also analyzed. During the first and the twelfth weeks of the experimental protocol, the oral glucose tolerance test and insulin tolerance test were performed and demonstrated insulin resistance (P < 0.05) in the HFD group. Although food intake (g) was lower (P < 0.05) in the HFD group compared with the control group, the concentration of total cholesterol, low‐density lipoprotein, C‐reactive protein and liver weight were all significantly higher. The kinase inhibitor of κB, c‐Jun N‐terminal kinase and protein kinase B expressions were determined in the liver and skeletal muscle. After an insulin stimulus, the HFD group demonstrated decreased (P = 0.05) hepatic protein kinase B expression, whereas the kinase inhibitor of κB phospho/total ratio was elevated in the HFD muscle (P = 0.02). In conclusion, the isocaloric intake from the HFD induced insulin resistance, associated with impaired insulin signalling in the liver and an inflammatory response in the muscle. Copyright © 2012 John Wiley & Sons, Ltd.     

Insulin Action,Regional Fat,and Myocyte Lipid: Altered Relationships with Increased Adiposity

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Research Methods and Procedures: Myocyte triglyceride content (¹H‐magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 ± 7.8 years) with a broad range of adiposity (BMI 28.6 ± 4.1 kg/m², range 20.1 to 37.6 kg/m²). Results: Relationships between insulin‐stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut‐point, insulin‐stimulated glucose disposal correlated negatively to all regional body fat measures (all p ≤ 0.004), serum triglycerides and free fatty acids (p < 0.02), and both soleus intramyocellular lipid (p = 0.003) and vastus lateralis triglyceride (p = 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin‐stimulated glucose disposal in more overweight men (r = ?0.576, p = 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut‐points or measures of adiposity. Discussion: Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.