Marie-Ève Piché

Regional body fat distribution and metabolic profile in postmenopausal women

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

The transcriptome of human epicardial, mediastinal and subcutaneous adipose tissues in men with coronary artery disease.

Background The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. Methods and Results Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects. Conclusions Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD.

Changes in predicted cardiovascular disease risk after biliopancreatic diversion surgery in severely obese patients

OBJECTIVE To determine the impact of biliopancreatic diversion with duodenal switch (BPD-DS) surgery on cardiovascular risk profile and predicted cardiovascular risk in severely obese patients. MATERIALS/METHODS We compared 1-year follow-up anthropometric and metabolic profiles in severely obese who underwent BPD-DS (n = 73) with controls (severely obese without surgery) (n =3 3). The 10-year predicted risk for coronary heart disease (CHD) was estimated using the Framingham risk-tool. We assigned 10-year and lifetime predicted risks to stratify subjects into 3 groups: 1) high short-term predicted risk (≥ 10% 10-year risk or diagnosed diabetes), 2) low short-term (<10% 10-year risk)/low lifetime predicted risk or 3) low short-term/high lifetime predicted risk. RESULTS During the follow-up period, body weight and body mass index decreased markedly in the surgical group (-52.1 ± 1.9 kg and -19.0 ± 0.6 kg/m(2) respectively, p<0.001) vs. (-0.7 ± 1.0 kg and -0.3 ± 0.4 kg/m(2), p = 0.51). Weight loss in the surgical group was associated with a reduction in HbA1C (6.2% vs. 5.1%), HOMA-IR (61.5 vs. 9.3), all lipoprotein levels, as well as blood pressure (p<0.001). The 10-year CHD predicted risk decreased by 43% in women and 33% in men, whereas the estimated CHD risk in the non surgical group did not change. Before surgery, none of the women and only 18% of men showed low short-term/low lifetime predicted risk, whereas a significant proportion of subjects had high short-term predicted risk (36% in women and 12% in men). Following surgery, 52% of women and 55% of men have a low short-term/low lifetime predicted risk. CONCLUSIONS These results highlight the cardiovascular benefits of BPD-DS and suggest a positive impact on predicted CHD risk in severely obese patients. Long-term studies are needed to confirm our results and to ascertain the effects on CHD risk estimates after BPD-DS surgery.

The Contribution of Visceral Adiposity and Mid-Thigh Fat-Rich Muscle to the Metabolic Profile in Postmenopausal Women

This study explored the relationship between muscle fat infiltration derived from mid‐thigh computed tomography (CT) scan, central fat distribution and insulin sensitivity in postmenopausal women. Mid‐thigh CT scans were used to measure low attenuation muscle surface (LAMS) (0–34 Hounsfield units (HU)), which represented a specific component of fat‐rich muscle. Whole‐body insulin sensitivity (M/I) was evaluated by an euglycemic‐hyperinsulinemic clamp. A group of 103 women aged 57.0 ± 4.4 years was studied. Women with higher levels of LAMS presented higher metabolic risk features, particularly elevated fasting, 2‐h plasma glucose (2hPG) concentrations and diminished M/I (P < 0.05). To further study the contribution of muscle fat infiltration and central adiposity on metabolic parameters, we divided the whole group based on the median of LAMS and visceral adipose tissue (VAT). As expected, the best metabolic profile was found in the Low‐LAMS/Low‐VAT group and the worst in the High‐LAMS/High‐VAT group. Women with Low‐LAMS/High‐VAT presented similar metabolic risks to those with High‐LAMS/High‐VAT. There was no difference between High‐LAMS/Low‐VAT and Low‐LAMS/Low‐VAT, which presents the most healthy metabolic and glycemic profiles as reflected by the lowest levels of cardiovascular disease risk variables. This suggests that High‐LAMS/Low‐VAT is also at low risk of metabolic deteriorations and that High‐LAMS, only in the presence of High‐VAT seems associated with deteriorated risks. Although increased mid‐thigh fat‐rich muscle was related to a deteriorated metabolic profile, VAT appears as a more important contributor to alterations in the metabolic profile in postmenopausal women.

The WHO and NCEP/ATPIII Definitions of the Metabolic Syndrome in Postmenopausal Women: Are They So Different?

BACKGROUND The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). METHODS One hundred and eight postmenopausal women (56.9 +/- 4.2 years; 28.5 +/- 5.9 kg/m(2)) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers. RESULTS The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO. CONCLUSIONS These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.

Relationship between eating behaviours and food and drink consumption in healthy postmenopausal women in a real-life context

Associations between eating behaviours and dietary variables have not been thoroughly investigated in healthy postmenopausal women in a real life uncontrolled context. To investigate how eating behaviours (cognitive dietary restraint, disinhibition and susceptibility to hunger) were associated with food and drink consumption, energy density and meal pattern in 112 healthy postmenopausal women (age 56.8 (SD 4.4) years) not on.hormonal therapy. Women completed a 3 d weighed food record and filled out the Three-Factor Eating Questionnaire. The sample was divided according to the median of the distribution of cognitive dietary restraint and disinhibition (9 and 6 respectively). Both subgroups of women with high restraint level (presenting either high or low disinhibition) consumed a diet with a lower energy density than subgroups of women with lower restraint level. Women with high restraint-low disinhibition had a lower consumption of red meat and processed meat and a lower consumption of diet soft drinks than women with low restraint-high disinhibition. They were also characterised by a higher intake of whole grains than women with high restraint-high disinhibition and than women with lower restraint level (with either high or low disinhibition). Women with high restraint-high disinhibition levels showed differences in dietary variables when compared with subgroups of women with lower restraint level, namely for refined grains and diet soft drinks. We conclude that in healthy postmenopausal women, dietary consumption of specific food and drink may be related to particular eating behaviours. Women with high restraint and low disinhibition levels generally showed the most healthy dietary pattern.

Impaired fasting glucose vs. glucose intolerance in pre-menopausal women: distinct metabolic entities and cardiovascular disease risk?

Background  Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT.

Plasma adiponectin concentration is strongly associated with VLDL-TG catabolism in postmenopausal women

BACKGROUND AND AIMS To investigate associations between plasma adiponectin concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women. METHODS AND RESULTS This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[²H₅] glycerol values obtained following the administration of a ²H₅-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r=-0.50; p=0.005) and positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR. CONCLUSIONS Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism.

Associations between circulating free fatty acids, visceral adipose tissue accumulation, and insulin sensitivity in postmenopausal women.

The aims of the study were to evaluate the contribution of visceral adipose tissue (AT) accumulation and insulin sensitivity to the determination of circulating free fatty acid (FFA) concentrations measured during a 2-hour euglycemic-hyperinsulinemic clamp and to verify whether elevated FFAs are associated with other components of the metabolic syndrome in postmenopausal women. This cross-sectional study included 115 postmenopausal women (46-68 years old). Visceral AT was estimated by computed tomography. Insulin sensitivity was assessed by a 2-hour euglycemic-hyperinsulinemic clamp. Free fatty acid concentration was measured in the fasting state and every 30 minutes during the clamp. Fasting plasma glucose and 2-hour plasma glucose were measured by an oral glucose tolerance test. Visceral AT was associated positively and insulin sensitivity negatively with FFA area under the curve (AUC) measured during the clamp. Women with high visceral AT accumulation and low insulin sensitivity had higher FFA AUC than women with high visceral AT accumulation and high insulin sensitivity or women with low visceral AT combined with either low or high insulin sensitivity. Free fatty acid AUC was positively associated with triglyceride (r = 0.25, P < .05), fasting plasma glucose (r = 0.26, P < .01), 2-hour plasma glucose (r = 0.27, P < .01), and diastolic blood pressure (r = 0.21, P < .05) independently of visceral AT and insulin sensitivity. In postmenopausal women, the presence of both high visceral AT and low insulin sensitivity is needed to observe an elevated FFA AUC. Moreover, FFA AUC is associated with some components of the metabolic syndrome, independently of visceral AT and insulin sensitivity.

Visceral adipose tissue accumulation and cardiovascular disease risk profile in postmenopausal women with impaired glucose tolerance or type 2 diabetes.

Objective  Women with impaired glucose tolerance (IGT) and type 2 diabetes (T2D) are more at risk of cardiovascular disease. The aim of this study was to test the hypothesis that increased visceral adipose tissue (VAT) could explain to a large extent alterations in the cardiovascular disease risk profile of postmenopausal women with IGT or T2D.