Restoration of acute insulin response in T2DM subjects 1 month after biliopancreatic diversion

Objective: Biliopancreatic diversion (BPD) restores normal glucose tolerance in a few weeks in morbid obese subjects with type 2 diabetes, improving insulin sensitivity. However, there is less known about the effects of BPD on insulin secretion. We tested the early effects of BPD on insulin secretion in obese subjects with and without type 2 diabetes. Methods and Procedures: Twenty‐one consecutive morbid obese subjects, 9 with type 2 diabetes (T2DM) and 12 with normal fasting glucose (NFG) were evaluated, just before and 1 month after BPD, by measuring body weight (BW), glucose, adipocitokines, homeostasis model assessment of insulin resistance (HOMA‐IR), acute insulin response (AIR) to e.v. glucose and the insulinogenic index adjusted for insulin resistance ([ΔI5/ΔG5]/HOMA‐IR). Results: Preoperatively, those with T2DM differed from those with NFG in showing higher levels of fasting glucose, reduced AIR (57.9 ± 29.5 vs. 644.9 ± 143.1 pmol/l, P < 0.01) and reduced adjusted insulinogenic index (1.0 ± 0.5 vs. 17.6 ± 3.9 1/mmol², P < 0.001). One month following BPD, in both groups BW was reduced (by ～11%), but all subjects were still severely obese; HOMA‐IR and leptin decreased significanlty, while high‐molecular weight (HMW) adiponectin and adjusted insulinogenic index increased. In the T2DM group, fasting glucose returned to non‐diabetic values. AIR did not change in the NFG group, while in the T2DM group it showed a significant increase (from 58.0 ± 29.5 to 273.8 ± 47.2 pmol/l, P < 0.01). In the T2DM group, the AIR percentage variation from baseline was significantly related to changes in fasting glucose (r = 0.70, P = 0.02), suggesting an important relationship exists between impaired AIR and hyperglycaemia. Discussion: BPD is able to restore AIR in T2DM even just 1 month after surgery. AIR restoration is associated with normalization of fasting glucose concentrations.     

Glucose regulation in captive Pongo pygmaeus abeli,P. p. pygmaeus,andP. p. abeli x P. p. pygmaeus orangutans

Intravenous glucose tolerance tests (IVGTT) were performed on 30 anesthetized, captive Sumatran (Pongo pygmaeus abeli), Bornean (P. p. pygmaeus), and hybrid (P. p. ablie x P. p. pygmaeus) orangutans, and fasted blood samples were taken from two additional juvenile orangutans in 11 U.S. zoos from 1989 to 1997. The age range of animals was 3.5 to 40.5 years. Plasma and serum samples were assayed for glucose and insulin concentrations. Glucose disappearance rate (K_G), an index of glucose tolerance, was calculated, as were the early (acute) and second phase insulin responses to administered glucose. The mean ± SE (and median) fasting glucose and insulin concentrations were 113 ± 16 mg/dL (90 mg/dL) and 45 ± 7 μU/mL (27 μU/mL), respectively. Two animals previously suspected to be diabetic were easily identified by their markedly elevated fasting glucose concentrations (380 and 562 mg/dL) and relatively low fasted insulin concentrations (21 and 14 μU/mL); their insulin responses during the IVGTTs were also low or non‐detectable. Without these diabetics, the mean ± SE (median) fasting glucose concentration was 92 ± 18 mg/dL (89 mg/dL). Two animals, ages 18 and 40, were identified as potentially pre‐diabetic based on age, adiposity, elevated fasted glucose (116 and 137 mg/dL, respectively), and elevated fasted insulin concentrations (114 and 217 μU/mL, respectively). In addition, nearly half of the animals of varying ages, all sub‐species and both sexes exhibited delayed or attenuated acute insulin responses during the IVGTTs, resulting in lower K_G (P < 0.04) and suggesting propensity for glucose intolerance in captive orangutans. Glucose and insulin concentrations and insulin responses to glucose did not differ between females on hormonal contraception regimes and those not receiving treatment. Zoo Biol 19:193–208, 2000. © 2000 Wiley‐Liss, Inc.     

Plasma Adiponectin Levels in High Risk African‐Americans with Normal Glucose Tolerance,Impaired Glucose Tolerance,and Type 2 Diabetes**

Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR (r = ?0.502, p = 0.046) and with HOMA‐β cell function (r = ?0.498, p = 0.042) but not with the percentage body fat (r = ?0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.     

Analysis of Obesity and Hyperinsulinemia in the Development of Metabolic Syndrome: San Antonio Heart Study

Objective: To use standardized cut‐offs of body mass index (BMI), waist circumference, waist‐to‐hip ratio, and fasting insulin levels to predict the development of metabolic disorders and metabolic syndrome. Research Methods and Procedures: We performed an 8‐year follow‐up study of 628 non‐Hispanic whites and 1340 Mexican Americans, ages 25 to 64 years, from the second cohort of the San Antonio Heart Study. We defined metabolic disorders as dyslipidemia (triglycerides ≥2.26 mM or high‐density lipoprotein <0.91 mM in men and <1.17 mM in women), hypertension (blood pressure ≥140/≥90 mm Hg, or receiving antihypertensive medications), and type 2 diabetes (fasting glucose ≥7.0 mM, 2‐hour test glucose ≥11.1 mM, or receiving anti‐diabetic medications). People with at least two metabolic disorders were defined as having metabolic syndrome. Results: High waist‐to‐hip ratio and fasting insulin levels were significant predictors of developing metabolic syndrome. High anthropometric indices remained significant predictors of metabolic syndrome after adjusting for fasting insulin. Waist circumference, BMI, and insulin had similar areas under the receiver operating characteristic curves (0.74 to 0.76). Further multivariate analyses combining these indices showed minimal increase in prediction. Of subjects who had a combination of high BMI (≥30 kg/m²) and high waist circumference (above “Action Level 2”), 32% developed metabolic syndrome, compared with 10% of subjects with both low BMI and low waist circumference. Discussion: These findings support the National Institutes of Health recommendations for reducing the risk of metabolic syndrome. Adjustment for baseline fasting insulin levels had only a small effect on the ability of anthropometric indices to predict the metabolic syndrome.     

Independent Evolution of Heart Autonomic Function and Insulin Sensitivity During Weight Loss

In order to investigate the improvement of insulin resistance and cardiac autonomic function along massive weight loss, 12 obese women were evaluated before, and 3 and 12 months after Roux‐en‐Y gastric bypass. The 12‐month values were compared to those of BMI‐matched controls. Insulin sensitivity was assessed by euglycemic clamp and the cardiac autonomic function by the analysis of the Heart Rate Variability (HRV). After surgery, glucose uptake progressively increased from 4.3 ± 0.5 mg/kg lean body mass (LBM)/min preoperative (pre‐op) to 4.9 ± 0.5 and 7.0 ± 0.5, 3‐ and 12‐month postoperative (post‐op) (P = 0.04 and P = 0.006 vs. pre‐op), whereas the cardiac autonomic function showed a biphasic pattern. HRV values increased 3 months post‐op, and decreased at 12 months, thus indicating an early sympathetic withdrawal followed by a later reactivation (e.g., the standard deviation of the normal‐to‐normal intervals was 116 ± 7 ms in pre‐op, 161 ± 10 at 3 months, P = 0.008 vs. pre‐op, and 146 ± 15 at 12 months, P = 0.03 vs. pre‐op and P = 0.02 vs. 3 m). Insulin sensitivity was significantly related to body weight (P = 0.02), whereas the cardiac indexes were significantly linked to the profile of energy intake (e.g., HRV triangular index vs. energy intake P = 0.003). No significant relationship linked insulin sensitivity to the cardiac autonomic indexes. Insulin sensitivity and cardiac parameters of the 12‐month post‐op patients were similar to their matched controls. During massive weight loss, the cardiac autonomic deregulation and insulin resistance improved concomitantly but independently from each other. Our results suggest that the extent of the improvement is associated with the final body weight.     

The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and lipid metabolism

Objective : Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber‐rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non‐obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates. Research Methods and Procedures : Eleven healthy, non‐obese and 10 obese subjects completed two 4‐week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber‐rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases. Results : After the modified diet phase, body weight was significantly lower in both the non‐obese and obese subjects (non‐obese, 57.0 ± 2.9 vs. 56.1 ± 2.8 kg, p = 0.001; obese, 67.7 ± 2.1 vs. 65.7 ± 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 ± 0.5 vs. 26.0 ± 0.6 kg/m², p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low‐density lipoprotein cholesterol (p < 0.05), and C‐peptide (p < 0.05) concentrations in the obese subjects. Discussion : These results indicate that fiber‐rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.     

Alcohol Consumption in the Severely Obese: Relationship with the Metabolic Syndrome

Objective: The aim of this study was to examine the association between the clinical and biochemical features of the metabolic syndrome and quantity and type of alcohol intake in the severely obese. Research Methods and Procedures: A cross‐sectional study was performed in 486 consecutive severely obese subjects. Data on alcohol consumption was collected by serial clinical interviews and a questionnaire. The relationship between alcohol intake and the clinical and serum chemistry features of the metabolic syndrome was analyzed by multiple statistical techniques. Laboratory measures included lipid profile, fasting blood glucose, hemoglobin A1c, and fasting serum insulin. An indirect index of insulin resistance was calculated using the log‐transformed fasting insulin and glucose product. Results: There were 486 subjects, 84% women, with a mean age of 40.6 ± 10 years (range, 16 to 71 years) and a body mass index of 45.3 ± 7 kg/m² (range, 34 to 77 kg/m²). Alcohol consumers (N = 276) showed a marked reduction in the adjusted odds ratio of type 2 diabetes (odds ratio = 0.29; 95% confidence interval, 0.16 to 0.55) compared with rare or nonconsumers (N = 210). There was a U‐shaped relationship between the amount and frequency of alcohol consumption and fasting triglyceride, fasting glucose, hemoglobin A1c, and index of insulin resistance measurements. Consumers of <100 g/wk had more favorable measures. The effect was attenuated when diabetics were excluded from the analysis. Timing of alcohol consumption did not influence outcome measures. Discussion: Light‐to‐moderate alcohol consumption is associated with a lower prevalence of type 2 diabetes, reduced insulin resistance, and more favorable vascular risk profile in the severely obese. We would propose that light to moderate alcohol consumption should not be discouraged in the severely obese.     

Glucose response to an oral glucose tolerance test predicts weight change in non-diabetic subjects

Objective: Glucose exerts a dual action in the regulation of energy balance, consisting of inhibition of energy intake and stimulation of energy expenditure. Whether blood glucose affects long‐term regulation of body weight in humans remains to be established. We sought to test the hypothesis that the post‐challenge glucose response is a predictor of weight change. Research Methods and Procedures: We performed a prospective analysis of the impact of glucose response to an oral glucose tolerance test (OGTT) and a mixed‐meal test (MT) on subsequent changes in body weight (BW) on 253 Pima Indians (166 men and 87 women) with normal glucose regulation at baseline and follow‐up (follow‐up: 7 ± 4 years). Main outcome measures included BW change (total, percent, and annual), plasma glucose and insulin concentrations during OGTT and MT [total and incremental areas under the curve (AUCs)], resting metabolic rate (RMR; indirect calorimetry), and insulin action (euglycemic‐hyperinsulinemic clamp). Results: Total and incremental glucose AUCs during the OGTT (but not the MT) were negatively associated with BW change (total, percent, and annual), both before and after adjusting for sex, age, initial BW, follow‐up time, insulin action, RMR, fasting plasma glucose and insulin concentrations, and insulin response. Total and incremental glucose AUCs during the OGTT were independent determinants of final BW with age, initial BW, follow‐up time, fasting plasma insulin concentrations, and RMR. Discussion: Higher post‐challenge glucose response protects against BW gain in subjects with normal glucose regulation. We propose that this action may be because of the effect of glucose on food intake and/or thermogenesis.     

Adipocyte Differentiation‐related Protein in Human Skeletal Muscle: Relationship to Insulin Sensitivity

Objective: To determine whether adipocyte differentiation‐related protein (ADRP), a lipid droplet—associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non‐diabetic (OND) and obese diabetic (OD) subjects. Research Methods and Procedures: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A_1C, fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting. Results: ADRP was highly expressed in SkM from OND (4.4 ± 1.54 AU/10 μg, protein, n = 10) and OD (5.02 ± 1.33 AU/10 μg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 ± 2.15 AU/10 μg to 9.92 ± 1.57 AU/10 μg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 ± 1.07 AU/10 μg, n = 6) displayed up‐regulation of ADRP expression (to 9.27 ± 2.76 AU/10 μg, p < 0.025). Discussion: ADRP is the predominant lipid droplet—associated protein in SkM, and low ADRP expression is up‐regulated in circumstances of improved glucose tolerance. Up‐regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.     

Short‐Term Effects of Dietary Fatty Acids on Muscle Lipid Composition and Serum Acylcarnitine Profile in Human Subjects

In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short‐term increases in dietary PA or OA would result in corresponding changes in the FA composition of skeletal muscle diacylglycerol (DAG) and triacylglycerol (TAG) and/or the specific FA selected for β‐oxidation. Healthy males (N = 12) and females (N = 12) ingested a low‐PA diet for 7 days. After fasting measurements of the serum acylcarnitine (AC) profile, subjects were randomized to either high‐PA (HI PA) or low‐PA/high‐OA (HI OA) diets. After 7 days, the fasting AC measurement was repeated and a muscle/fat biopsy obtained. FA composition of intramyocellular DAG and TAG and serum AC was measured. HI PA increased, whereas HI OA decreased, serum concentration of 16:0 AC (P < 0.001). HI OA increased 18:1 AC (P = 0.005). HI PA was associated with a higher PA/OA ratio in muscle DAG and TAG (DAG: 1.03 ± 0.24 vs. 0.46 ± 0.08, P = 0.04; TAG: 0.63 ± 0.07 vs. 0.41 ± 0.03, P = 0.01). The PA concentration in the adipose tissue DAG (µg/mg adipose tissue) was 0.17 ± 0.02 in those receiving the HI PA diet (n = 6), compared to 0.11 ± 0.02 in the HI oa group (n = 4) (P = 0.067). The relative PA concentration in muscle DAG and TAG and the serum palmitoylcarnitine concentration was higher in those fed the high‐PA diet.     

Fasting-based estimates of insulin sensitivity in overweight and obesity: a critical appraisal

Objective: To identify simple methods to estimate the degree of insulin resistance. Research Methods and Procedures: The performance of a wide range of fasting‐based index estimates of insulin sensitivity was compared by receiver operating characteristic analysis (area under curves and their 95% confidence intervals) against the M value from euglycemic insulin clamp studies collected in the San Antonio (non‐Hispanic whites and Hispanic residents of San Antonio, TX) and European Group for the Study of Insulin Resistance (non‐diabetic white Europeans) databases (n = 638). Results: Insulin resistance differed substantially between lean (BMI < 25 kg/m²), overweight or obese (BMI ≥ 25 kg/m²), and type 2 diabetic individuals. Estimates of insulin resistance were, therefore, assessed in each group separately. In the overweight and obese subgroup (n = 302), the receiver operating characteristic performance of fasting‐based indices varied from 0.72 (0.62 to 0.82), in the case of the insulin/glucose ratio, to 0.80 (0.72 to 0.88) in the case of Belfiore free fatty acids. One superior method could not be identified; the confidence intervals overlapped, and no statistically significant differences emerged. All indices performed better when using the whole study population, with fasting plasma insulin, homeostatic model assessment, insulin/glucose ratio, quantitative insulin sensitivity check index, glucose/insulin ratio, Belfiore glycemia, revised quantitative insulin sensitivity check index, McAuley index, and Belfiore free fatty acids showing area under curves of 0.83, 0.90, 0.66, 0.90, 0.66, 0.90, 0.85, 0.83, and 0.86, respectively, because of the inclusion of very insulin sensitive (lean) and very insulin resistant cases (diabetic subjects). Discussion: In conclusion, a superior fasting‐based index estimate to distinguish between the presence and absence of insulin resistance in overweight and obesity could not be identified despite the use of the large datasets.     

Obesity,Fasting Plasma Insulin,and C‐Reactive Protein Levels in Healthy Children

Objective: Obesity is associated with hyperinsulinemia and increased level of C‐reactive protein in older children and adults, but little is known about these relationships in very young children. We examined these relationships in healthy 2‐ to 3‐year‐old children. Research Methods and Procedures: Analyses were performed on data from 491 healthy 2‐ to 3‐year‐old Hispanic children enrolled in a dietary study conducted in New York City, 1992 to 1995. Results: Body mass index (BMI), ponderal index, and sum of four skinfolds were highly correlated (r > 0.75) in both boys and girls. Fasting insulin and glucose levels were only modestly correlated (r = 0.37 for boys and r = 0.28 for girls; p < 0.001 for both), but essentially all of the variability in a calculated index of insulin resistance was attributable to variability in fasting insulin level. The correlations of BMI with fasting insulin level were r = 0.16 (p < 0.05) in boys and r = 0.14 (p < 0.05) in girls. In separate multivariate regression analyses adjusting for age and sex, BMI and ponderal index were associated with fasting plasma insulin level (p < 0.001 for both obesity measures). In multivariate regression analyses adjusting simultaneously for age, sex, and either BMI or ponderal index, fasting insulin level, but not these obesity measures, was associated with C‐reactive protein level. Discussion: Obesity is associated with higher fasting insulin level, and fasting insulin is associated with C‐reactive protein level, in healthy 2‐ to 3‐year‐old children.     

Normal Insulin Sensitivity in Lean Offspring of Obese Parents

Objective: Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents. Research Methods and Procedures: Twenty‐one lean offspring of nonobese subjects [(OL) 22 ± 3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram_FFM; where FFM represents fat‐free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (χ² = 30.2, p = 0.001) concordance of BMI between parents and offspring. Results: In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value = 45 ± 12 (OOb) vs. 47 ± 17 μmol/min per kilogram_FFM (OL)], insulin‐induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose‐induced thermogenesis. Discussion: The metabolic similarity between lean offspring of obese parents and those of nonobese parents suggests that insulin resistance and its correlates are not co‐inherited with the predisposition to develop obesity.     

Insulin Sensitivity Determines the Effectiveness of Dietary Macronutrient Composition on Weight Loss in Obese Women

Objective: To determine whether macronutrient composition of a hypocaloric diet can enhance its effectiveness and whether insulin sensitivity (Si) affects the response to hypocaloric diets. Research Methods and Procedures: Obese nondiabetic insulin‐sensitive (fasting insulin < 10 μU/mL; n = 12) and obese nondiabetic insulin‐resistant (fasting insulin > 15 μU/mL; n = 9) women (23 to 53 years old) were randomized to either a high carbohydrate (CHO) (HC)/low fat (LF) (60% CHO, 20% fat) or low CHO (LC)/high fat (HF) (40% CHO, 40% fat) hypocaloric diet. Primary outcome measures after a 16‐week dietary intervention were: changes in body weight (BW), Si, resting metabolic rate, and fasting lipids. Results: Insulin‐sensitive women on the HC/LF diet lost 13.5 ± 1.2% (p < 0.001) of their initial BW, whereas those on the LC/HF diet lost 6.8 ± 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, among the insulin‐resistant women, those on the LC/HF diet lost 13.4 ± 1.3% (p < 0.001) of their initial BW as compared with 8.5 ± 1.4% (p < 0.001) lost by those on the HC/LF diet (p < 0.04 between two groups). These differences could not be explained by changes in resting metabolic rate, activity, or intake. Overall, changes in Si were associated with the degree of weight loss (r = ?0.57, p < 0.05). Discussion: The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women. For maximal benefit, the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si.     

Alcohol intake, insulin resistance, and abdominal obesity in elderly men

Objective: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. Research Methods and Procedures: In a population‐based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insulin secretion (early insulin response), or adiposity [BMI, waist circumference (WC), waist‐to‐hip ratio]. Alcohol intake was self‐reported (questionnaire) and was assessed from a validated 7‐day dietary record. The cross‐sectional associations were evaluated using multivariable linear regression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. Results: In multivariable models, self‐estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (β‐coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p = 0.02) and waist‐to‐hip ratio (0.006 [0.002–0.009], p = 0.003). The association with WC and waist‐to‐hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. Discussion: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers.     

Liraglutide, a once-daily human glucagon-like peptide-1 analog, minimizes food intake in severely obese minipigs

Objectives: To evaluate the efficacy of liraglutide, a new, stable, once‐daily human analog of glucagon‐like peptide‐1, in a new animal model of obesity. Research Methods and Procedures: Liraglutide was administered subcutaneously once daily (7 μg/kg for 7 weeks) to six female obese Göttingen minipigs. Food intake and feeding patterns were monitored using a novel automated feeding system that allowed continuous recording of food intake. Results: Food intake was strongly suppressed. A steady‐state level of reduced food intake was achieved within 3 weeks and was maintained for the remaining 4 weeks of the treatment period. During the 4‐week steady‐state period with liraglutide treatment, daily food intake was 7.3 ± 0.3 megajoule (MJ) compared with 18.4 ± 0.6 MJ in the pre‐treatment period and 19.2 ± 0.5 MJ in the post‐treatment period (p < 0.001). The food intake in the treatment period was equivalent to the amount of food that would have been offered to normal‐weight pigs for maintenance. Body weight decreased 4.3 ± 1.2 kg (4% to 5%) during the 7 weeks of treatment and increased 7.0 ± 1.0 kg during the 7 weeks of post‐treatment (p < 0.01). Appetite suppression was quickly reversed within 4 days after termination of liraglutide administration. Discussion: Overall, liraglutide was well tolerated and had a profound and persistent anorectic effect that resulted in weight loss. These results, in conjunction with the previously established glucose‐lowering efficacy of liraglutide, suggest that the anorectic actions of liraglutide will be very important in clinical trials of both obese patients with type 2 diabetes and obese non‐diabetic patients.     

Genetic Effects on Postprandial Variations of Inflammatory Markers in Healthy Individuals

Circulating levels of inflammatory markers predict the risk of cardiovascular disease (CVD), mediated perhaps in part by dietary fat intake, through mechanisms only partially understood. To evaluate post‐fat load changes in inflammatory markers and genetic influences on these changes, we administered a standardized high‐fat meal to 838 related Amish subjects as part of the Heredity and Phenotype Intervention (HAPI) Heart Study and measured a panel of inflammatory markers, including C‐reactive protein (CRP), interleukin‐1β (IL‐1β), matrix metalloproteinase‐1 and ‐9 (MMP‐1 and MMP‐9), and white blood cell (WBC) count, before and 4 h after fat challenge (CRP prechallenge only). Heritabilities (h² ± s.d.) of basal inflammatory levels ranged from 16 ± 8% for MMP‐9 (P = 0.02) to 90 ± 7% for MMP‐1 (P < 0.0001). Post‐fat load, circulating levels of WBC, MMP‐1, and MMP‐9 increased by 16, 32, and 43% (all P < 0.0001), with no significant changes in IL‐1β. Postprandial changes over the 4‐h period were modestly heritable for WBC (age‐ and sex‐adjusted h² = 14 ± 9%, P = 0.04), but the larger MMP‐1 and MMP‐9 changes appeared to be independent of additive genetic effects. These results reveal that a high‐fat meal induces a considerable inflammatory response. Genetic factors appear to play a significant role influencing basal inflammatory levels but to have minimal influence on post‐fat intake inflammatory changes.     

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans

Objective:

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Design and methods:

The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6‐7 days on a weight‐maintenance diet (control, C; n = 55) and 6‐7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10).

Results:

F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI.

Conclusions:

Short‐term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short‐term regulation of hepatic glucose metabolism by simple carbohydrates.     

The Influence of Higher Protein Intake and Greater Eating Frequency on Appetite Control in Overweight and Obese Men

The purpose of this study was to determine the effects of dietary protein intake and eating frequency on perceived appetite, satiety, and hormonal responses in overweight/obese men. Thirteen men (age 51 ± 4 years; BMI 31.3 ± 0.8 kg/m²) consumed eucaloric diets containing normal protein (79 ± 2 g protein/day; 14% of energy intake as protein) or higher protein (138 ± 3 g protein/day; 25% of energy intake as protein) equally divided among three eating occasions (3‐EO; every 4 h) or six eating occasions (6‐EO; every 2 h) on four separate days in randomized order. Hunger, fullness, plasma glucose, and hormonal responses were assessed throughout 11 h. No protein × eating frequency interactions were observed for any of the outcomes. Independent of eating frequency, higher protein led to greater daily fullness (P < 0.05) and peptide YY (PYY) concentrations (P < 0.05). In contrast, higher protein led to greater daily ghrelin concentrations (P < 0.05) vs. normal protein. Protein quantity did not influence daily hunger, glucose, or insulin concentrations. Independent of dietary protein, 6‐EO led to lower daily fullness (P < 0.05) and PYY concentrations (P < 0.05). The 6‐EO also led to lower glucose (P < 0.05) and insulin concentrations (P < 0.05) vs. 3‐EO. Although the hunger‐related perceived sensations and hormonal responses were conflicting, the fullness‐related responses were consistently greater with higher protein intake but lower with increased eating frequency. Collectively, these data suggest that higher protein intake promotes satiety and challenge the concept that increasing the number of eating occasions enhances satiety in overweight and obese men.     

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.