Erik P. Kirk

Dietary Fat and Carbohydrates Differentially Alter Insulin Sensitivity During Caloric Restriction

BACKGROUND & AIMS We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity. METHODS Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (<50 g/day) energy-deficit diet. A euglycemic-hyperinsulinemic clamp, muscle biopsy specimens, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling, and intrahepatic triglyceride (IHTG) content before, after 48 hours, and after approximately 11 weeks (7% weight loss) of diet therapy. RESULTS At 48 hours, IHTG content decreased more in the LC than the HC diet group (29.6% +/- 4.8% vs 8.9% +/- 1.4%; P < .05) but was similar in both groups after 7% weight loss (LC diet, 38.0% +/- 4.5%; HC diet, 44.5% +/- 13.5%). Basal glucose production rate decreased more in the LC than the HC diet group at 48 hours (23.4% +/- 2.2% vs 7.2% +/- 1.4%; P < .05) and after 7% weight loss (20.0% +/- 2.4% vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05). CONCLUSIONS Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet‐induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss‐independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (body mass index [BMI]: 38.1 ± 4.6 kg/m2) with NAFLD were randomized to 16 weeks of exercise training (45%‐55% V̇O2peak, 30‐60 minutes × 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL‐TG and apolipoprotein B‐100 (apoB‐100) secretion rates. Exercise training resulted in a 10.3% ± 4.6% decrease in IHTG content (P < 0.05), but did not change total body weight (103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training) or percent body fat (38.9% ± 2.1% before and 39.2% ± 2.1% after training). Exercise training did not change the hepatic VLDL‐TG secretion rate (17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training) or VLDL‐apoB‐100 secretion rate (1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training). Conclusion: Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD. (HEPATOLOGY 2012;55:1738–1745)

Pathogenesis and Pathophysiology of the Cardiometabolic Syndrome

The cardiometabolic syndrome represents a cluster of metabolic abnormalities that are risk factors for cardiovascular disease. The mechanism(s) responsible for developing the cardiometabolic syndrome is not known, but it is likely that multi‐organ insulin resistance, which is a common feature of the cardiometabolic syndrome, is involved. Insulin resistance is an important risk factor for type 2 diabetes and can cause vasoconstriction and renal sodium reabsorption, leading to increased blood pressure. Alterations in adipose tissue fatty acid and adipokine metabolism are involved in the pathogenesis of insulin resistance. Excessive rates of fatty acid release into the bloodstream can impair the ability of insulin to stimulate muscle glucose uptake and suppress hepatic glucose production. Noninfectious systemic inflammation associated with adipocyte and adipose tissue macrophage cytokine production can also cause insulin resistance. In addition, increased free fatty acid delivery to the liver can stimulate hepatic very low‐density lipoprotein triglyceride production, leading to dyslipidemia.

Minimal resistance training improves daily energy expenditure and fat oxidation.

UNLABELLED Long-term resistance training (RT) may result in a chronic increase in 24-h energy expenditure (EE) and fat oxidation to a level sufficient to assist in maintaining energy balance and preventing weight gain. However, the impact of a minimal RT program on these parameters in an overweight college-aged population, a group at high risk for developing obesity, is unknown. PURPOSE We aimed to evaluate the effect of 6 months of supervised minimal RT in previously sedentary, overweight (mean +/- SEM, BMI = 27.7 +/- 0.5 kg x m(-2)) young adults (21.0 +/- 0.5 yr) on 24-h EE, resting metabolic rate (RMR), sleep metabolic rate (SMR), and substrate oxidation using whole-room indirect calorimetry 72 h after the last RT session. METHODS Participants were randomized to RT (one set, 3 d x wk(-1), three to six repetition maximums, nine exercises; N = 22) or control (C, N = 17) groups and completed all assessments at baseline and at 6 months. RESULTS There was a significant (P < 0.05) increase in 24-h EE in the RT (527 +/- 220 kJ x d(-1)) and C (270 +/- 168 kJ x d(-1)) groups; however, the difference between groups was not significant (P = 0.30). Twenty-four hours of fat oxidation (g x d(-1)) was not altered after RT; however, reductions in RT assessed during both rest (P < 0.05) and sleep (P < 0.05) suggested increased fat oxidation in RT compared with C during these periods. SMR (8.4 +/- 8.6%) and RMR (7.4 +/- 8.7%) increased significantly in RT (P < 0.001) but not in C, resulting in significant (P < 0.001) between-group differences for SMR with a trend for significant (P = 0.07) between-group differences for RMR. CONCLUSION A minimal RT program that required little time to complete (11min per session) resulted in a chronic increase in energy expenditure. This adaptation in energy expenditure may have a favorable impact on energy balance and fat oxidation sufficient to assist with the prevention of obesity in sedentary, overweight young adults, a group at high risk for developing obesity.

Weight Loss Reduces Liver Fat and Improves Hepatic and Skeletal Muscle Insulin Sensitivity in Obese Adolescents

Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic–euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI ≥95th percentile for age and sex; age 15.3 ± 0.6 years) before and after moderate diet‐induced weight loss (8.2 ± 2.0% of initial body weight). Weight loss caused a 61.6 ± 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 ± 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 ± 45% increase in insulin‐mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet‐induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity‐related metabolic complications during a standard medical evaluation.

Time course for changes in aerobic capacity and body composition in overweight men and women in response to long-term exercise: the Midwest Exercise Trial (MET)

OBJECTIVE: To determine the time course for changes in aerobic capacity, body weight (BW), and composition in overweight adults in response to a supervised exercise trial with a targeted energy expenditure of 2000 kcal week−1.DESIGN: The Midwest Exercise Trial (MET) was a randomized, controlled, 16-month verified, supervised exercise trial. Aerobic exercise progressed to 45 min day−1, 5 days week−1 over 6-months and was then maintained for 10 months. Controls maintained their normal physical activity and all participants maintained ad libitum diets.SUBJECTS: A total of 131 participants were randomized to exercise or control groups and 74 completed the intervention and all laboratory testing.MEASUREMENTS: At baseline and months 4, 9, 12, and 16, aerobic capacity (VO2max) was measured by indirect calorimetry, BW by digital scale, and fat weight and fat-free weight by hydrostatic weighing.RESULTS: Aerobic capacity (ml kg−1 min−1) increased (P<0.05) from baseline (39.2±5.2, mean±s.d.) to 9 months (48.8±4.3) in exercising men as well as women (32.8±4.2–39.6±5.5) with no significant changes occurring at 12 or 16 months. From baseline to 9 months BW (94.0±12.6–88.7±9.7 kg) and fat weight (26.8±6.8–21.8±4.5 kg) significantly decreased in exercising men with no changes occurring at 12 or 16 months. There were no changes in fat-free weight across the 16 months for exercising men or for BW or composition in exercising women. Further, there were no significant changes for the control men for aerobic capacity, BW, or body composition across 16 months. Women in the control group showed significant increases in weight of 2.9±5.5 kg and fat weight of 2.1±4.8 kg at 16 months only.CONCLUSIONS: We recommend that investigations that use exercise without diet as the stimulus for weight loss have at least a 9-month duration to provide sufficient time for the full effects to be realized, should such effects be present.

Reporting quality of randomized trials in the diet and exercise literature for weight loss

BackgroundTo adequately assess individual studies and synthesize quantitative research on weight loss studies, transparent reporting of data is required. The authors examined the reporting quality of randomized trials in the weight loss literature, focusing exclusively on subject characteristics as they relate to enrollment, allocation, and follow-up.MethodsAn extensive literature review, which included a computerized search of the MEDLINE database, manual searches of bibliographic references, and cross-referencing of 92 review articles was conducted. A checklist, based on CONSORT recommendations, was used to collect information on whether or not authors reported age, gender, co-morbid disease, medication use, race/ethnicity, and postmenopausal status. Also tracked was whether or not initial and final sample size was reported and stratified by gender.ResultsOf 604 possible articles, 231 articles met eligibility criteria. Important subject characteristics were not reported as the following breakdown indicates: age (11%), gender (4%), race/ethnicity (86%), co-morbid disease states (34%), and medication use (92%). Additionally, 21% of articles failed to report initial sample size by gender while 69% neglected to report final sample size by gender.ConclusionInadequate reporting can create difficulties with interpretation and can lead to biased results receiving false credibility. The quality of reporting for weight loss studies needs considerable improvement.

Author contacts for retrieval of data for a meta-analysis on exercise and diet restriction.

OBJECTIVES The mode of contact and response levels of authors who had been asked to provide missing or incomplete data for a systematic review on diet and exercise interventions for weight loss was examined. METHODS We contacted authors by electronic mail, letter, or both. Survival analyses were performed with the Kaplan-Meier method to determine differences in the proportion of responders over time among the different modes of contact and to determine whether response rates differed between authors from the United States and those from other countries. Logistic regression was used to determine whether the number of items requested and publication date influenced the likelihood of response. RESULTS Two hundred forty-one (39.9 percent) studies had missing or incomplete data (e.g., sample size, age, caloric restriction, exercise amount, and so on). We were unable to locate ninety-five authors (39.4 percent). Of the remaining authors, forty-six authors (31.5 percent) responded to information requests. Time to respond differed by contact method (p < .05): e-mail (3 +/- 3 days), letter (27 +/- 30 days), and both (13 +/-12 days). Response rates from U.S. authors did not differ from those of other countries. CONCLUSIONS Our study suggests poor success in the acquisition of essential information. Given considerable time and resources, weight loss studies require improved reporting standards to minimize the relatively unsuccessful attempt to contact authors for important and necessary information.

Dietary predictors of visceral adiposity in overweight young adults

The purpose of the present study was to determine the dietary predictors of visceral adipose tissue (VAT) area in overweight young adults. A total of 109 young adults (fifty males and fifty-nine females) ate ad libitum in a university cafeteria for 14 d. All food and beverages consumed in the cafeteria were measured using observer-recorded weighed plate waste. Food consumption outside the cafeteria (i.e. snacks) was assessed by multiple-pass 24 h recall procedures. VAT was determined using computed tomography. Stepwise regression demonstrated that the best predictor of visceral adiposity in women was total dietary fat (P <or= 0.05). In men, the model for predicting visceral adiposity included Ca and total dietary fat. We concluded that total dietary fat is the best predictor of VAT area in both men and women. While this relationship was independent in women, in men there was a synergistic relationship between dietary fat consumption and Ca consumption in predicting VAT.

The 1-Mile Walk Test is a Valid Predictor of VO2max and is a Reliable Alternative Fitness Test to the 1.5-Mile Run in U.S. Air Force Males

The purpose of this study was to assess the validity of the 1-mile walk (Rockport Walk Test) as a predictor of VO(2max) and determine whether the 1-mile walk is a reliable alternative to the 1.5-mile run in moderately fit to highly fit U.S. Air Force males. Twenty-four (33.0 +/- 1.5 years) males completed a maximal treadmill VO(2max) (50.3 +/- 1.4 mL/ kg/min), 1-mile walk, and 1.5-mile run. For the 1-mile walk, there were no significant differences between measured and predicted VO(2max) (p = 0.177, r = 0.817). There were no significant differences (p = 0.573) between points scored in the Air Force Fitness Test for the 1-mile walk and 1.5-mile run tests. In conclusion, the 1-mile walk test is a valid predictor of VO(2max) and can be used as an alternative fitness test to the 1.5-mile run in assessing cardiovascular fitness in Air Force males.