OBJECTIVELow-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population.RESEARCH DESIGN AND METHODSThe Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation.RESULTSWBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference.CONCLUSIONSThis study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.
Objective: The gastric bypass-induced quantitative and qualitative modifications of energy intake (En In, kcal=day) and their impact on body weight (bw) loss were evaluated. The factors influencing energy intake and body weight loss were also investigated. Design: Longitudinal study. Setting: University Hospital of Geneva. Subjects: Fifty obese women undergoing a Roux-en-Y gastric bypass. Results: The reduction of EnIn was significantly related to bw loss expressed either in kg or as percentage correction of excess bw (P < 0.01 for both), whereas the post-operative modifications of diet composition did not play a role. Age and initial bw significantly influenced bw loss (P < 0.0001 and P < 0.001, respectively), as shown by multiple regression analysis. Patients were divided into four sub-groups according to their age (under or over 35 y) and initial bw (under or over 120 kg). ANOVA showed that under 35-y-old subjects reduced their EnIn significantly more than their older counterparts having similar bw (P < 0.02 and P < 0.05); consequently, bw loss, expressed in kg, was significantly (P < 0.0001 and P < 0.0005) larger in younger patients. Subjects with an initial bw over 120 kg lost significantly (P < 0.001 and P < 0.02) more weight as compared to patients with a smaller degree of obesity (under 120 kg) and similar age. Conclusions: Gastric bypass-induced body weight loss is mainly due to the reduction of EnIn, whereas the qualitative modifications of the diet do not play a role. Younger subjects have a greater capacity to reduce EnIn and, therefore, lose more weight. Pre-operative high degree of obesity leads to a larger weight reduction, probably because of a greater energy deficit.
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±4 kg/m 2 ) were investigated before, and 3 and 12 months 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 12 months ( p=0.03) as was MFN2 ( p=0.008 and p=0.03 at 3 and 12 months respectively), whereas UCP3 was reduced ( p=0.03) at 12 months. 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 12 months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3 months postoperatively ( p=0.001 vs before RYGB), remaining unchanged thereafter until 12 months. 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 RYGB.
Morbidly obese, normoglycaemic and normotensive young women have increased HR and low HRV, indicating an abnormal cardiac autonomic function and representing a risk factor for adverse cardiovascular events. A decrease of HRV parameters is associated with a progressive increase of body FM. Other metabolic and hormonal factors, characterising obesity, do not show an independent influence on these HRV alterations.
Objectives: The objective of this study was to define metabolic normality and to investigate the cardiometabolic profile of metabolically normal obese. Design: Cross-sectional study conducted at 21 research centers in Europe. Subjects: Normal body weight (nbw, n ¼ 382) and overweight or obese (ow/ob, n ¼ 185) subjects free from metabolic syndrome and with normal glucose tolerance, were selected among the Relationship between Insulin Sensitivity and Cardiovascular Disease study participants. Main outcome measures: Insulin sensitivity was assessed by the clamp technique. On the basis of quartiles in nbw subjects, the limits of normal insulin sensitivity and of normal fasting insulinemia were established. Subjects with normal insulin sensitivity and fasting insulin were defined as metabolically normal. Results: Among ow/ob subjects, 11% were metabolically normal vs 37% among nbw, Po0.0001. Ow/ob subjects showed increased fasting insulin (P ¼ 0.0009), low-density lipoprotein cholesterol (LDL-cholesterol) (P ¼ 0.004), systolic (P ¼ 0.0007) and diastolic (P ¼ 0.001) blood pressure, as compared with nbw. When evaluating the contribution of body mass index (BMI), hyperinsulinemia and insulin resistance, BMI showed an isolated effect on high-density lipoprotein (P ¼ 0.007), high-sensitivity C-reactive protein (Po0.0001), systolic (P ¼ 0.002) and diastolic (P ¼ 0.008) blood pressures. BMI shared its influence with insulinemia on total cholesterol (P ¼ 0.04 and 0.003, respectively), LDL-cholesterol (P ¼ 0.003 and 0.006, respectively) and triglycerides (P ¼ 0.02 and 0.001, respectively). Conclusion: In obese subjects, fasting insulin should be taken into account in the definition of metabolic normality. Even when metabolically normal, obese subjects could be at increased risk for cardiometabolic diseases. Increased BMI, alone or with fasting insulin, is the major responsible for the less favorable cardio-metabolic profile.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.