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Introduction: We have previously shown that hyperbaric oxygen treatment (HBOT) increased insulin sensitivity in men who were obese or overweight, both with and without type 2 diabetes. The aim of this study was to test whether this insulinsensitising effect is seen in hyperbaric air (HA). Methods: Men with type 2 diabetes who were obese or overweight were randomised to two groups: HBOT (n = 13) or HA (n = 11). A hyperinsulinaemic euglycaemic glucose clamp (80 mU·m-2·min-1) was performed at baseline and during hyperbaric intervention. Both groups were compressed to 203 kPa (two atmospheres absolute) for 90 minutes followed by a linear 30-minute decompression. The HBOT group breathed oxygen via a hood while the HA group breathed chamber air. Insulin sensitivity was assessed from the glucose infusion rate (GIR) during the last 30 minutes in the hyperbaric chamber (SS1) and the first 30 minutes after exit (SS2). Data were analysed for within-group effect by paired student t-test and between-group effect by one-way ANOVA. Results: HBOT increased GIR by a mean 26% at SS1 (P = 0.04) and 23% at SS2 (P = 0.018). There was no significant change in GIR during or after HA. A between-group effect was evident for the change in GIR at SS1 in HBOT vs HA (P = 0.036). Conclusions: The pathway by which insulin sensitivity is increased in men with type 2 diabetes requires the high oxygen partial pressures of HBOT and should be further investigated. Insulin sensitivity was not changed in hyperbaric air. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies using a hyperinsulinaemic, euglycaemic glucose clamp have demonstrated an increase in peripheral insulin sensitivity in men with and without Type-2 diabetes mellitus on the third and thirtieth hyperbaric oxygen treatment (HBOT) session. In two studies using different techniques for assessment of insulin sensitivity, we investigated the onset and duration of this insulin-sensitising effect of HBOT. Methods: Men who were obese or overweight but without diabetes were recruited. One study performed a hyperinsulinaemic euglycaemic glucose clamp (80 mU.m-2.min-1) at baseline and during the first HBOT exposure (n = 9) at a pressure of 203 kPa. Data were analysed by paired t-test. The other study assessed insulin sensitivity by a frequently sampled intravenous glucose tolerance test (FSIGT) at three time points: baseline, during the third HBOT and 24-hours post-HBOT (n = 9). Results were analysed by repeated-measures ANOVA. Results: There was a significant 23% increase in insulin sensitivity by clamp measured during the first HBOT exposure. The FSIGT showed no significant changes in insulin sensitivity. Conclusions: The hyperinsulinaemic, euglycaemic glucose clamp demonstrated a significant increase in peripheral insulin sensitivity during a single, 2-hour HBOT session in a group of men who were obese or overweight but without diabetes. As an alternate technique for assessing insulin sensitivity during HBOT, the FSIGT failed to show any changes during the third HBOT and 24-hours later, however modification of the study protocol should be considered. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition.Methods: Women with overweight (n = 88; 50 ± 1 years, BMI 32.3 ± 0.5 kg/m2 ) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic-euglycemic clamp, weight, body composition, and plasma markers were assessed following a "fed" day (12-hour fast) and a 24-hour fast (IF only).Results: IF70 displayed greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P ≤ 0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24-hour fast transiently reduced insulin sensitivity.Conclusions: When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss. [ABSTRACT FROM AUTHOR]

Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35–80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (β = 0.409, p<0.001), TT (β = 0.560, p<0.001), fT4 (β = 0.067, p = 0.019) and SHBG, and negative associations between triglycerides (β = -0.112, p<0.001), abdominal fat mass (β = -0.068, p = 0.032) and E2 (β = -0.058, p = 0.050) and SHBG. In longitudinal analysis the positive determinants of SHBG at 4.9 years were age (β = 0.406, p = <0.001), TT (β = 0.461, p = <0.001), and fT4 (β = 0.040, p = 0.034) and negative determinants were triglycerides (β = -0.065, p = 0.027) and abdominal fat mass (β = -0.078, p = 0.032). Taken together these data suggest low SHBG is a marker of abdominal obesity and increased serum triglycerides, conditions which are known to have been associated with low testosterone and low T4. [ABSTRACT FROM AUTHOR]

Eating during the night may increase the risk for obesity and type 2 diabetes in shift workers. This study examined the impact of either eating or not eating a meal at night on glucose metabolism. Participants underwent four nights of simulated night work (SW1–4, 16:00–10:00 h, <50 lux) with a daytime sleep opportunity each day (10:00–16:00 h, <3 lux). Healthy males were assigned to an eating at night (NE;n = 4, meals; 07:00, 19:00 and 01:30 h) or not eating at night (NEN;n = 7, meals; 07:00 h, 09:30, 16:10 and 19:00 h) condition. Meal tolerance tests were conducted post breakfast on pre-night shift (PRE), SW4 and following return to day shift (RTDS), and glucose and insulin area under the curve (AUC) were calculated. Mixed-effects ANOVAs were used with fixed effects of condition and day, and their interactions, and a random effect of subject identifier on the intercept. Fasting glucose and insulin were not altered by day or condition. There were significant effects of day and condition × day (bothp < 0.001) for glucose AUC, with increased glucose AUC observed solely in the NE condition from PRE to SW4 (p = 0.05) and PRE to RTDS (p < 0.001). There was also a significant effect of day (p = 0.007) but not condition × day (p = 0.825) for insulin AUC, with increased insulin from PRE to RTDS in both eating at night (p = 0.040) and not eating at night (p = 0.006) conditions. Results in this small, healthy sample suggest that not eating at night may limit the metabolic consequences of simulated night work. Further study is needed to explore whether matching food intake to the biological clock could reduce the burden of type 2 diabetes in shift workers. [ABSTRACT FROM PUBLISHER]

Individuals conceived by in vitro fertilization (IVF) may be at increased risk of cardio-metabolic disorders. We recently reported that IVF conceived male mice displayed impaired glucose metabolism at normal and high body weights. In this study, we examined glucose metabolism in mature female C57BL/6J mice that were conceived by natural conception (NC), by ovarian stimulation (OS) or by IVF following chow or high-fat diet (HFD) for 8 weeks. By design, litter size was comparable between groups, but interestingly the birth weight of IVF and OS females was lower than NC females (p≤0.001). Mature IVF female mice displayed increased fasting glucose as compared to NC and OS mice, irrespective of diet. Mature IVF and OS mice were also more susceptible to the metabolic consequences of high fat diet as compared with NC females, with impaired glucose tolerance (p≤0.01), whereas peripheral insulin resistance and increased hepatic expression of gluconeogenic genes Ppargc1α, Pck1 and G6pc was observed in IVF mice only (p<0.05). This study suggests that ovarian stimulation alone and IVF program distinct metabolic effects in females, but that high fat diet may be required to unmask these effects. This study adds to the growing body of literature that assisted reproduction procedures may increase the risk of developing type 2 diabetes in an obesity prone environment. [ABSTRACT FROM AUTHOR]

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% had 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. Diabetes 59:627-633, 2010 [ABSTRACT FROM AUTHOR]

Insulin resistance is a key defect associated with obesity and type-2 diabetes. The precise factors that lead to insulin resistance have not been elucidated fully, but there is a strong association between insulin resistance and inappropriate lipid accumulation in insulin-target tissues. Over the past decade, several studies have reported changes in markers of mitochondrial metabolism in insulin-resistant individuals. These observations have led to the theory that compromised mitochondrial oxidative function, particularly in skeletal muscle, causes excess lipid deposition and the development of insulin resistance. Here, we review the latest findings regarding the link between mitochondrial metabolism and insulin action and, in particular, highlight several recent studies that call into question the cause-and-effect relationship between mitochondrial dysfunction and insulin resistance. [Copyright &y& Elsevier]

OBJECTIVE--Compared with nondiabetic subjects, type 2 diabetic subjects are metabolically inflexible with impaired fasting fat oxidation and impaired carbohydrate oxidation during a hyperinsulinemic clamp. We hypothesized that impaired insulin-stimulated glucose oxidation is a consequence of the lower cellular glucose uptake rate in type 2 diabetes. Therefore, we compared metabolic flexibility to glucose adjusted for glucose disposal rate in nondiabetic versus type 2 diabetic subjects and in the latter group after 1 year of lifestyle intervention (the Look AHEAD [Action For Health in Diabetes] trial). RESEARCH DESIGN AND METHODS--Macronutrient oxidation rates under fasting and hyperinsulinemic conditions (clamp at 80 mU/m² per min), body composition (dual-energy X-ray absorptiometry), and relevant hormonal/metabolic blood variables were assessed in 59 type 2 diabetic and 42 nondiabetic individuals matched for obesity, sex, and race. Measures were repeated in diabetic participants after weight loss. RESULTS--Metabolic flexibility to glucose (change in respiratory quotient [RQ]) was mainly related to insulin-stimulated glucose disposal rate (R² = 0.46, P < 0.0001) with an additional 3% of variance accounted for by plasma free fatty acid concentration at the end of the clamp (P = 0.03). The impaired metabolic flexibility to glucose observed in type 2 diabetic versus nondiabetic subjects (ΔRQ 0.06 ± 0.01 vs. 0.10 ± 0.01, respectively, P < 0.0001) was no longer observed after adjusting for glucose disposal rate (P = 0.19). Additionally, the increase in metabolic flexibility to glucose after weight loss was accounted for by the concomitant increase in insulin-stimulated glucose disposal rate. CONCLUSIONS--This study suggests that metabolic inflexibility to glucose in type 2 diabetic subjects is mostly related to defective glucose transport. [ABSTRACT FROM AUTHOR]

Objective: It is unclear if resting metabolic rate (RMR) and spontaneous physical activity (SPA) decrease in weight-reduced non-obese participants. Additionally, it is unknown if changes in SPA, measured in a respiratory chamber, reflect changes in free-living physical activity level (PAL).Research Methods and Procedures: Participants (N = 48) were randomized into 4 groups for 6 months: calorie restriction (CR, 25% restriction), CR plus structured exercise (CR+EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), low-calorie diet (LCD, 890 kcal/d supplement diet until 15% weight loss, then weight maintenance), and control (weight maintenance). Measurements were collected at baseline, Month 3, and Month 6. Body composition and RMR were measured by DXA and indirect calorimetry, respectively. Two measures of SPA were collected in a respiratory chamber (percent of time active and kcal/d). Free-living PAL (PAL = total daily energy expenditure by doubly labeled water/RMR) was also measured. Regression equations at baseline were used to adjust RMR for fat-free mass and SPA (kcal/d) for body weight.Results: Adjusted RMR decreased at Month 3 in the CR group and at Month 6 in the CR+EX and LCD groups. Neither measure of SPA decreased significantly in any group. PAL decreased at Month 3 in the CR and LCD groups, but not in the CR+EX group, who engaged in structured exercise. Changes in SPA in the chamber and free-living PAL were not related.Discussion: Body weight is defended in non-obese participants during modest caloric restriction, evidenced by metabolic adaptation of RMR and reduced energy expenditure through physical activity. [ABSTRACT FROM AUTHOR]