From metabolic normality to cardiometabolic risk factors in subjects with obesity.

The aim of the study was to evaluate the 3 years incidence of cardiometabolic risk factors, such as impaired fasting glucose, reduced high-density lipoprotein (HDL)-cholesterol, increased plasma triglycerides or blood pressure as well as impaired glucose tolerance in overweight or obese (ow/ob) and normal body weight (nbw) subjects metabolically normal at baseline. Subjects from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study were analyzed. We analyzed 284 nbw and 152 ow/ob subjects who, at baseline, did not show any of the above-mentioned cardiometabolic risk factors. At 3 years, these parameters were re-evaluated. Intima-media thickness (IMT) of the common carotid artery (CCA) was echographically measured. At follow-up, the incidence of one or more cardiometabolic risk factors was 57.2% in ow/ob vs. 31.7% in nbw (P < 0.0001). After adjustment for age, sex, menopause status, lifestyle parameters, insulin sensitivity, and fasting insulinemia, BMI remained significantly linked to the development of one or more cardiometabolic risk factors (P = 0.02). An increased BMI at follow-up was significantly associated with the development of cardiometabolic alterations, in both nbw and ow/ob groups (P = 0.04). Ow/ob subjects who, at 3 years follow-up, remained metabolically normal, showed a less favourable cardiometabolic profile, when compared to nbw counterparts. In ow/ob metabolically normal males and females, intima-media of the common carotid at follow-up was thicker than in nbw (P = 0.03 for males, P = 0.04 for females). In conclusion, metabolically normal obese subjects show a higher incidence of cardiometabolic risk factors, in a short follow-up period. Weight gain is significantly associated with the development of these factors, in both nbw and ow/ob subjects.

Multi-factorial approach associated with a new 'on/off' Orlistat® use in a weight loss maintenance programme: 4 years follow-up.

AIM: To assess the efficacy of a specific long-term programme for weight loss maintenance using a new 'on/off' Orlistat approach in obese subjects who previously lost more than 10% of their body weight. METHODS: 50 patients were followed up during 4 years; 34 completed the study. Subjects were followed up by physicians trained in obesity management. Anthropometrical, biological and psychological parameters were measured. Insulin sensitivity was evaluated by euglycaemic insulin clamp. Orlistat was given in case of weight relapse more than 2.5%. Subjects could take Orlistat on a voluntary basis for special occasions. RESULTS: The BMI of completers remained stable (29.5 ± 0.9 vs. 30.6 ± 1.0 kg/m(2)). 73% of completers maintained 10% or more of their weight loss. Subjects from the no-regain group improved most of their parameters while the regain group did not. Insulin sensitivity was negatively linked to body weight during the follow up (p < 0.01, r(2) = 0.20). A negative relationship has been found between extent of the previous weight loss and the evolution of body weight during the 4 years follow-up (p < 0.01, r(2) = 0.26). Orlistat intake showed a body fat lowering effect (p < 0.05). CONCLUSION: 73% of subjects maintained more than 10% of their weight loss. Subject with a large weight loss amount are at high risk for weight regain. The Orlistat 'on/off' intake regarding his lowering body fat mass effect seems to be efficient.

Do obese patients after weight loss become metabolically normal?

OBJECTIVE: To compare the metabolic cardiovascular risk factors of obese patients after weight loss and 4-year weight loss maintenance afterwards against a matched control group of subjects with a stable body weight and without history of weight loss. METHOD: 50 obese non-diabetic subjects in the study group who previously lost 10% or more of their weight and afterwards entered a 4-year weight loss maintenance programme were matched by age, BMI and sex and compared to 50 weight-stable subjects without history of weight loss. The comparison between both groups was done in term of anthropometrical, metabolic and biological characteristics, early atherosclerosis and insulin sensitivity. RESULTS: Anthropometrical, metabolic and biological characteristics were similar between the weight loss group and the control matched group. However, insulin sensitivity was still significantly lower in the weight loss than in the matched control group (p = 0.02). Intima media thickness (IMT) also was similar in both groups. We found that lower atherosclerosis measured by IMT at the level of the carotid is associated with better insulin sensitivity (p < 0.05). After the 4-year weight loss maintenance programme, insulin sensitivity improved in the post-weight loss group from 7.9 ± 3.2 to 8.4 ± 3.6 mg/kg/min. CONCLUSION: All cardiometabolic parameters of obese subjects, except for insulin sensitivity, normalised completely after weight loss. The latter was improved by a weight loss maintenance programme if successfully completed.

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.

AIMS: Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. METHODS AND RESULTS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively. CONCLUSIONS: Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.

[Enlarged waist circumference and cardiovascular risk factors]. / Périmètre abdominal augmenté et facteurs de risque cardiovasculaire.

Obesity is a recognized risk factor for cardiovascular diseases. As evaluated by body mass index (BMI), obesity is associated with increased morbidity and mortality due to chronic diseases, like type 2 diabetes, coronary artery disease and stroke. It has been shown that not only the quantity of the fat mass but also the fat mass distribution is important. Furthermore, the fat tissue deposition at visceral level, as measured by waist circumference, is a risk factor for cardio-metabolic diseases. The waist circumference is easy to measure and reflect the visceral adipose tissue which is a cardio-metabolic risk factor Abdominal fat accumulation induces a less favorable cardio-metabolic profile, even in normal body weight subjects with waist circumference within the normal range.

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.