Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids?

To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED) as well as quality of life (QoL) and to elucidate the role of endocannabinoids in metabolic syndrome (MS). In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Among completers (n = 87), body weight decreased in 35 patients (-9.1 ± 8.6 kg), remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg). 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA) values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08), fasting glucose (p < 0.0001, R2 = 0.12), total cholesterol (p = 0.001, R2 = 0.11), triglycerides (p = 0.001, R2 = 0.11), LDL-cholesterol (p = 0.03, R2 = 0.05) as well as depression score (p = 0.002, R2 = 0.29). Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL

Persistent Correlation of Ghrelin Plasma Levels with Body Mass Index Both in Stable Weight Conditions and during Gastric-bypass-induced Weight Loss

Background: Studies done on serial changes in plasma ghrelin levels after gastric bypass (GBP) have yielded contrasting results since decreased, unchanged, or increased levels have been reported in the literature. This study investigates whether or not GBP has an inhibitory effect on fasting ghrelin levels independently of weight loss. Methods: Fasting ghrelin levels were measured in 115 stable body weight females, classified as normal body weight (NW; body mass index (BMI) 50kg/m2). Results: Each obese subgroup showed significantly lower ghrelin levels as compared to both NW (p < 0.0001) and OW subjects (p < 0.05 or 0.005); however, no significant differences were observed within the three obese subgroups. Forty-nine obese patients underwent a GBP. Plasma ghrelin, measured at 3, 6, and 12months after GBP, significantly increased from the sixth month on (p < 0.0001). When patients were classified, at each postoperative time point, according to their actual BMI, ghrelin was significantly (p = 0.0002) related to postoperative BMI and not significantly different from ghrelin measured in stable body weight conditions. Conclusions: Fasting ghrelin displays an inversely significant correlation with BMI in both stable body weight conditions and after GBP. No evidence was found that GBP had an effect on fasting ghrelin levels, independent of weight los

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene ( PGC1A ) during weight loss is related to insulin sensitivity but not to energy expenditure

Aims/hypothesis: We investigated whether skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1A; also known as PPARGC1A) and its target mitofusin-2 (MFN2), as well as carnitine palmitoyltransferase-1 (CPT1; also known as carnitine palmitoyltransferase 1A [liver] [CPT1A]) and uncoupling protein (UCP)3, are involved in the improvement of insulin resistance and/or in the modification of energy expenditure during surgically induced massive weight loss. Materials and methods: Seventeen morbidly obese women (mean BMI: 45.9 ± 4kg/m2) were investigated before, and 3 and 12months after, Roux-en-Y gastric bypass (RYGB). We evaluated insulin sensitivity by the euglycaemic-hyperinsulinaemic clamp, energy expenditure and substrate oxidation by indirect calorimetry, and muscle mRNA expression by PCR. Results: Post-operatively, PGC1A was enhanced at 3 (p = 0.02) and 12months (p = 0.03) as was MFN2 (p = 0.008 and p = 0.03 at 3 and 12months respectively), whereas UCP3 was reduced (p = 0.03) at 12months. CPT1 did not change. The expression of PGC1A and MFN2 were strongly (p < 0.0001) related. Insulin sensitivity, which increased after surgery (p = 0.002 at 3, p = 0.003 at 12months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3months post-operatively (p = 0.001 vs before RYGB), remaining unchanged thereafter until 12months. CPT1 and UCP3 were not significantly related to the modifications of energy expenditure or of lipid oxidation rate. Conclusions/interpretation: Weight loss upregulates PGC1A, which in turn stimulates MFN2 expression. MFN2 expression significantly and independently contributes to the improvement of insulin sensitivity. UCP3 and CPT1 do not seem to influence energy expenditure after RYG

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass

Aims/hypothesis: The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. Methods: A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (%Δ L: H). Results: Preoperative %Δ L: H showed a significant (p=0.0009, r 2=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r 2=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, %Δ L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account. Conclusions/interpretation: The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reductio

Troglitazone in combination with sulphonylurea improves glycaemic control in Type 2 diabetic patients inadequately controlled by sulphonylurea therapy alone. Troglitazone Study Group.

AIM: The aim of this study was to investigate the effectiveness of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist developed primarily for the treatment of Type 2 diabetes mellitus (DM)), 100 or 200mg/day, in terms of glycaemic control, lipid profile and tolerability, when given in addition to existing sulphonylurea therapy. METHODS: A 16-week, randomized, parallel-group placebo-controlled trial in 259 Type 2 diabetic patients already on sulphonylurea therapy. RESULTS: At week 16, adjusted geometric mean HbA1c with troglitazone 100mg (7.7%; P=0.023) and 200mg (7.4%; P<0.001) was lower with sulphonylurea alone (8.2%). At all weeks, adjusted geometric mean fasting serum glucose levels were lower in both troglitazone groups, compared with sulphonylurea alone (P=0.007 to P<0.001). At week 16, both troglitazone groups showed reductions in immune reactive insulin compared with sulphonylurea alone (200mg, 13%; P=0.032: 100mg, 5%; NS). Troglitazone reduced serum levels of nonesterified fatty acids at week 16 (100 g, 12%; P=0.042) and at all weeks (200mg, 17-24%; P=0.014 to P<0.001). The incidence of drug-related adverse events was similar in all groups (23-24% of patients). There was no apparent association between hypoglycaemia and the addition of troglitazone to sulphonylurea therapy. CONCLUSIONS: Troglitazone 100 or 200 mg added to usual sulphonylurea therapy in patients with Type 2 DM is associated with a significant improvement in glycaemic control, without altering the adverse-event profile of the sulphonylurea