Associations of leukocyte telomere length with body anthropometric indices and weight change in chinese women

Objective: This study evaluated associations of telomere length with various anthropometric indices of general and abdominal obesity, as well as weight change. Design and Methods: The study included 2,912 Chinese women aged 40‐70 years. Monochrome multiplex quantitative polymerase chain reaction was applied to measure relative telomere length. Results: Telomere length was inversely associated with body mass index (BMI), waist circumference, waist‐to‐height ratio, weight, and hip circumference (P_trend = 0.005, 0.004, 0.004, 0.010, and 0.026, respectively), but not waist‐to‐hip ratio (P_trend = 0.116) or height (P_trend = 0.675). Weight change since age 50 was further evaluated among women over age 55. Women who maintained their weight within ±5% since age 50, particularly within a normal range (BMI = 18.5‐24.9 kg/m²), or reduced their weight from overweight (BMI = 25‐29.9 kg/m²) or obesity (BMI ≥30 kg/m²) to normal range, had a longer mean of current telomere length than women who gained weight since age 50 (P_trend = 0.025), particularly those who stayed in obesity or gained weight from normal range or overweight to obesity (P = 0.023). Conclusion: Our findings show that telomere shortening is associated with obesity and that maintaining body weight within a normal range helps maintain telomere length.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

Fat Depot‐specific Impact of Visceral Obesity on Adipocyte Adiponectin Release in Women

Our objective was to examine omental and subcutaneous adipocyte adiponectin release in women. We tested the hypothesis that adiponectin release would be reduced to a greater extent in omental than in subcutaneous adipocytes of women with visceral obesity. Omental and subcutaneous adipose tissue samples were obtained from 52 women undergoing abdominal hysterectomies (age: 47.1 ± 4.8 years; BMI: 26.7 ± 4.7 kg/m²). Adipocytes were isolated and their adiponectin release in the medium was measured over 2 h. Measures of body fat accumulation and distribution were obtained using dual‐energy X‐ray absorptiometry and computed tomography, respectively. Adiponectin release by omental and subcutaneous adipocytes was similar in lean individuals; however, in subsamples of obese or visceral obese women, adiponectin release by omental adipocytes was significantly reduced while that of subcutaneous adipocytes was not affected. Omental adipocyte adiponectin release was significantly and negatively correlated with total body fat mass (r = ?0.47, P < 0.01), visceral adipose tissue area (r = ?0.50, P < 0.01), omental adipocyte diameter (r = ?0.43, P < 0.01), triglyceride levels (r = ?0.32, P ≤ 0.05), cholesterol/high‐density lipoprotein (HDL)‐cholesterol (r = ?0.31, P ≤ 0.05), fasting glucose (r = ?0.39, P ≤ 0.01), fasting insulin (r = ?0.36, P ≤ 0.05), homeostasis model assessment index (r = ?0.39, P ≤ 0.01), and positively associated with HDL‐cholesterol concentrations (r = 0.33, P ≤ 0.05). Adiponectin release from subcutaneous cells was not associated with any measure of adiposity, lipid profile, or glucose homeostasis. In conclusion, compared to subcutaneous adipocyte adiponectin release, omental adipocyte adiponectin release is reduced to a greater extent in visceral obese women and better predicts obesity‐associated metabolic abnormalities.     

Improvements in Coronary Heart Disease Risk Indicators by Alternate‐Day Fasting Involve Adipose Tissue Modulations

The ability of alternate‐day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10‐week trial with three consecutive dietary intervention phases: (i) 2‐week baseline control phase, (ii) 4‐week ADF controlled feeding phase, and (iii) 4‐week ADF self‐selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat‐free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low‐density lipoprotein cholesterol (LDL‐C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High‐density lipoprotein cholesterol (HDL‐C), C‐reactive protein, and homocysteine concentrations did not change. Decreases in LDL‐C were related to increased adiponectin (r = ?0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = ?0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post‐treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.     

Influence of age on the association of retinol-binding protein 4 with metabolic syndrome

Objective: The relationships of retinol‐binding protein 4 (RBP4) with insulin sensitivity and body fat distribution have been investigated in a few recent studies with conflicting results. This may have been due to differences in ages of the subjects in the different studies. The aim of this study was to investigate whether the association of RBP4 and insulin sensitivity and percent trunk fat are influenced by age. Methods and Procedures: Cross‐sectional analyses of 48 young subjects and 55 elderly subjects. Insulin sensitivity was determined by a hyperinsulinemic–euglycemic clamp. Body fat distribution was determined by a dual‐energy X‐ray absorptiometry (DXA). Results: In the young subjects, RBP4 levels were associated with insulin sensitivity (r = ?0.30, P = 0.04), percent trunk fat (r = 0.54, P < 0.001), triglycerides (r = 0.44, P = 0.003), low‐density lipoprotein (r = 0.38, P = 0.01). In contrast, in the elderly subjects there was no correlation between RBP4 levels and insulin sensitivity (r = ?0.18, P = 0.20), percent trunk fat (r = 0.00, P = 0.10), triglycerides (r = 0.25, P = 0.10), and low‐density lipoprotein (r = ?0.11, P = 0.47). Discussion: The associations of RBP4 with insulin sensitivity, percent trunk fat, and lipid levels are influenced by age.     

Impacts of Visceral Adipose Tissue and Subcutaneous Adipose Tissue on Metabolic Risk Factors in Middle‐aged Japanese

Regional fat distribution rather than overall fat volume has been considered to be important to understanding the link between obesity and metabolic disorders. We aimed to evaluate the independent associations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with metabolic risk factors in apparently healthy middle‐aged Japanese. Participants were 1,119 men and 854 women aged 38–60 years who were not taking medications for diabetes, hypertension, or dyslipidemia. VAT and SAT were measured by use of computed tomography (CT) scanning. VAT and SAT were significantly and positively correlated with each other in men (r = 0.531, P < 0.001) and women (r = 0.589, P < 0.001). In multiple regression analyses, either measure of abdominal adiposity (VAT or SAT) was positively associated with blood pressure, fasting plasma glucose, and log triglyceride (P < 0.001) and inversely with high‐density lipoprotein (HDL)‐cholesterol (P < 0.001). When VAT and SAT were simultaneously included in the model, the association of VAT with triglycerides was maintained (P < 0.001) but that of SAT was lost. The same was true for HDL‐cholesterol in women. For fasting plasma glucose, the association with VAT was strong (P < 0.001) and the borderline association with SAT was maintained (P = 0.060 in men and P = 0.020 in women). Both VAT and SAT were independently associated with blood pressure (P < 0.001). Further adjustment for anthropometric indices resulted in the independent association only with VAT for all risk factors. In conclusion, impacts of VAT and SAT differed among risk factors. VAT showed dominant impacts on triglyceride concentrations in both genders and on HDL‐cholesterol in women, while SAT also had an independent association with blood pressure.     

The Macrophage‐Specific Serum Marker,Soluble CD163, Is Increased in Obesity and Reduced After Dietary‐Induced Weight Loss

Objective: Soluble CD163 (sCD163) is a new macrophage‐specific serum marker elevated in inflammatory conditions. sCD163 is elevated in obesity and found to be a strong predictor of the development of type 2 diabetes. We investigated whether dietary intervention and moderate exercise was related to changes in sCD163 and how sCD163 is associated to insulin resistance in obesity. Design and Methods: Ninety‐six obese subjects were enrolled: 62 followed a very low energy diet (VLED) program for 8 weeks followed by 3‐4 weeks of weight stabilization, 20 followed a moderate exercise program for 12 weeks, and 14 were included without any intervention. Fasting blood samples and anthropometric measures were taken at baseline and after intervention. Thirty‐six lean subjects were included in a control group. Results: sCD163 was significantly higher in obese subjects (2.3 ± 1.0 mg/l) compared with lean (1.6 ± 0.4 mg/l, P < 0.001). Weight loss (11%) induced by VLED resulted in a reduction and partial normalization of sCD163 to 2.0 ± 0.9 mg/l (P < 0.001). Exercise for 12 weeks had no effect on sCD163. At baseline, sCD163 was significantly correlated with BMI (r = 0.46), waist circumference (r = 0.40), insulin resistance measured by the homeostasis model assessment (HOMA‐IR; r = 0.41; all P < 0.001), and the leptin‐to‐adiponectin ratio (r = 0.28, P < 0.05). In a multivariate linear regression analysis with various inflammatory markers, sCD163 (β = 0.25), adiponectin (β = ?0.24), and high sensitivity C‐reactive protein (hs‐CRP; β = 0.20) remained independently and significantly associated to HOMA‐IR (all P < 0.05). After further adjustment for waist circumference, only sCD163 was associated with HOMA‐IR (P < 0.05). Conclusion: The macrophage‐specific serum marker sCD163 is increased in obesity and partially normalized by dietary‐induced weight loss but not by moderate exercise. Furthermore, we confirm that sCD163 is a good marker for obesity‐related insulin resistance.     

25‐Hydroxyvitamin D Concentration Correlates With Insulin‐Sensitivity and BMI in Obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25‐hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin‐sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin‐sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin‐sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50 nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low‐density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin‐sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = ?0.58; P = 0.01), PTH (r = ?0.44; P < 0.01), insulin‐sensitivity (r = 0.43; P < 0.01), total (r = ?0.34; P = 0.030) and LDL (r = ?0.40; P = 0.023) (but not high‐density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin‐sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = ?0.52; P < 0.01), whereas insulin‐sensitivity was not significant. Our study suggested that there is no cause–effect relationship between vitamin D and insulin‐sensitivity. In obesity, both low 25(OH)D concentration and insulin‐resistance appear to be dependent on the increased body size.     

BMI and Rates of Suicide in the United States: An Ecological Analysis

BMI has been inversely associated with risk of completed suicide in several cohort studies, but putative mechanisms for this association and its generalizability throughout the United States are uncertain. We ascertained recent population‐based, state‐level data on rates of obesity, completed suicide (by method), firearm ownership, smoking, major depression, income, education, white race, and nonmetropolitan residence, compiled from federal agencies and surveys, and determined the adjusted population‐weighted correlations of statewide obesity rates with measures of completed and attempted suicide. Statewide prevalence of obesity was strongly inversely correlated with age adjusted suicide rate (multivariable‐adjusted r = ?0.66; P < 0.001). The correlation was somewhat stronger for rates of nonfirearm‐related (r = ?0.75; P < 0.001) than firearm‐related suicides (r = ?0.53; P < 0.001), and was of similar magnitude as the positive correlations of firearm prevalence with suicide rate (r = 0.75; P < 0.001) or of obesity with prevalence of diabetes (r = 0.41; P = 0.006). In analyses of fatal and nonfatal suicidal acts, obesity rates were inversely correlated with rates of suicidal acts using firearms (r = ?0.53; P = 0.02) and suffocation (r = ?0.76; P < 0.001) but not other methods. Obesity rates were also inversely correlated with the case–fatality ratios of acts using poisoning (r = ?0.51; P = 0.01). Thus, statewide rates of obesity are strongly inversely correlated with rates of completed suicide in multivariable analyses, a finding that appears to relate to fewer attempts by suffocation and a lower case–fatality ratio for poisonings, although the mechanism for the inverse correlation with firearm‐related suicides requires further elucidation.     

Defining Health‐Related Obesity in Prepubertal Children

Objective: The purpose of this study was to develop percentage of fat and waist circumference cut‐points in prepubertal children with the intention of defining obesity associated with cardiovascular disease (CVD) risk. Research Methods and Procedures: A cross‐sectional analysis of 87 prepubertal children aged 4 to 11 years was used. Percentage of body fat was determined by DXA. Waist circumference was measured to the nearest millimeter. Receiver Operating Characteristic analyses of percentage of fat and waist circumference were used to develop cut‐points for individuals with adverse levels of CVD risk factors. Results: The risk factors selected for analyses (i.e., fasting insulin, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, and total cholesterol/high‐density lipoprotein cholesterol) were significantly related to percentage of body fat and waist circumference. Likelihood ratios were used to identify percentage of fat and waist circumference cut‐points associated with adverse cardiovascular risk profiles. Two cut‐points, an upper cut‐point of 33% body fat and a lower cut‐point of 20% body fat, were derived. Waist circumference cut‐points indicative of adverse and normal risk‐factor profiles were 71 cm and 61 cm, respectively. Discussion: The data indicate that children with ≥33% body fat and children with a waist circumference ≥71 cm were more likely to possess an adverse CVD risk‐factor profile than a normal risk‐factor profile. The likelihood of children with <20% body fat or a waist circumference <61 cm possessing an adverse CVD risk‐factor profile as opposed to a normal risk‐factor profile was small. The cut‐points describe an adequate health‐related definition of childhood obesity.     

Calcium and Magnesium ATPase Activities in Women with Varying BMIs

Objective: Intracellular calcium (Ca) is increased in obese humans, and magnesium (Mg)‐ATPase activity is increased in monosodium glutamate‐induced obese rats. The aims of this study were to test the hypotheses that Ca‐ATPase activity is negatively correlated with BMI, and that Mg‐ATPase activity is positively correlated with BMI and Ca‐ATPase activity in obese women. Research Methods and Procedures: Thirty healthy adult women, with BMIs of 20 to 40, donated a single sample of whole blood and were interviewed as to medical history and family history of obesity. Erythrocyte membranes were isolated and assayed for Ca‐ATPase and Mg‐ATPase. Weight and height were self‐reported. Regression analysis was used to determine relationship between BMI and enzyme activity. Family history of obesity served as a covariant. Results: Ca‐ATPase was negatively correlated with increasing BMI (r = ? 0.38, p = 0.02). The relationship between BMI and Ca‐ATPase remained valid after controlling for family history of obesity (r = ?0.36, p = 0.03). There was a positive correlation between Mg‐ATPase activity and Ca‐ATPase (r = 0.42, p = 0.024), and this relationship remained valid after controlling for BMI and family history of obesity (r = 0.41, p = 0.03). Discussion: Ca‐ATPase activity decreases as BMI increases. Decreased ATPase activity may contribute to increased intracellular calcium, previously reported in obese persons. Further studies are needed to determine whether a drop in Ca‐ATPase activity can serve as a marker for the development of obesity.     

The Gene Expression of the Main Lipogenic Enzymes is Downregulated in Visceral Adipose Tissue of Obese Subjects

Contradictory findings regarding the gene expression of the main lipogenic enzymes in human adipose tissue depots have been reported. In this cross‐sectional study, we aimed to evaluate the mRNA expression of fatty acid synthase (FAS) and acetyl‐CoA carboxilase (ACC) in omental and subcutaneous (SC) fat depots from subjects who varied widely in terms of body fat mass. FAS and ACC gene expression were evaluated by real time‐PCR in 188 samples of visceral adipose tissue which were obtained during elective surgical procedures in 119 women and 69 men. Decreased sex‐adjusted FAS (?59%) and ACC (?49%) mRNA were found in visceral adipose tissue from obese subjects, with and without diabetes mellitus type 2 (DM‐2), compared with lean subjects (both P < 0.0001). FAS mRNA was also decreased (?40%) in fat depots from overweight subjects (P < 0.05). Indeed, FAS mRNA was significantly and positively associated with ACC gene expression (r = 0.316, P < 0.0001) and negatively with BMI (r = ?0.274), waist circumference (r = ?0.437), systolic blood pressure (r = ?0.310), serum glucose (r = ?0.277), and fasting triglycerides (r = ?0.226), among others (all P < 0.0001). Similar associations were observed for ACC gene expression levels. In a representative subgroup of nonobese (n = 4) and obese women (n = 6), relative FAS gene expression levels significantly correlated (r = 0.657, P = 0.034; n = 10) with FAS protein values. FAS protein levels were also inversely correlated with blood glucose (r = ?0.640, P = 0.046) and fasting triglycerides (r = ?0.832, P = 0.010). In conclusion, the gene expression of the main lipogenic enzymes is downregulated in visceral adipose tissue from obese subjects.     

The Lipid Accumulation Product and All‐cause Mortality in Patients at High Cardiovascular Risk: A PreCIS Database Study

The BMI is the most frequently used marker to evaluate obesity‐associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC ? 65) × TG (men) and (WC ? 58) × TG (women). We evaluated LAP and BMI as predictors of mortality in a high‐risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty‐eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low‐density lipoprotein‐cholesterol (LDL‐C) and high‐density lipoprotein‐cholesterol (HDL‐C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P < 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity.     

Leptin and Altitude in the Cardiovascular Diseases

Objective: The lower mortality from coronary ischemic disease in populations living at high altitude has been related to an increase of high‐density lipoprotein (HDL)‐cholesterol at altitude. Leptin has been proposed as a cardiovascular risk factor. We investigated whether leptin varies according to the altitude at which people live. Research Methods and Procedures: This was a cross‐sectional study of the first 889 people enrolled in a cohort study in the Canary Islands, Spain. The relationship among serum leptin, altitude, obesity, and other cardiovascular risk factors was analyzed by bivariate and multivariate tests. Results: Leptin levels showed an inverse correlation to altitude expressed in meters (r = ?0.10). Obese subjects had this leptin‐altitude association (r = ?0.19), but they also had a direct correlation of leptin to HDL‐cholesterol (r = 0.27) and an inverse correlation of leptin to the total cholesterol‐to‐HDL‐cholesterol ratio (r = ?0.34), triglycerides (r = ?0.29), apolipoprotein B (r = ?0.21), and glycemia (r = ?0.19). Nonobese subjects had only the leptin‐altitude association (r = ?0.11). The final regression model included altitude as predictor. Other associated variables were gender, physical activity, BMI, age, smoking (reducing leptin independently of BMI), alcohol, heart rate, and income. Discussion: Serum leptin level decreases when altitude increases, and this association could help to explain the lower cardiovascular mortality rate at high altitude. However, because in obese subjects there is a direct association of leptin with HDL‐cholesterol and an inverse association with the lipid atherogenic fractions, we suggest the hypothesis of different roles for bound and free leptin, with free leptin being a cardiovascular protective factor in obese people.     

Severe Obesity Is Associated With Impaired Arterial Smooth Muscle Function in Young Adults

The degree of arterial dilatation induced by exogenous nitrates (nitrate‐mediated dilatation, NMD) has been similar in obese and normal‐weight adults after single high‐dose glyceryl trinitrate (GTN). We examined whether NMD is impaired in obesity by performing a GTN dose‐response study, as this is a potentially more sensitive measure of arterial smooth muscle function. In this cross‐sectional study, subjects were 19 obese (age 31.0 ± 1.2 years, 10 male, BMI 44.1 ± 2.1) and 19 age‐ and sex‐matched normal‐weight (BMI 22.4 ± 0.4) young adults. Blood pressure (BP), triglycerides, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL)‐cholesterol, glucose, insulin, high‐sensitivity C‐reactive protein (hs‐CRP), carotid intima‐media thickness (CIMT), and flow‐mediated dilatation (FMD) were measured. After incremental doses of GTN, brachial artery maximal percent dilatation (maximal NMD) and the area under the dose‐response curve (NMD AUC) were calculated. Maximal NMD (13.4 ± 0.9% vs. 18.3 ± 1.1%, P = 0.002) and NMD AUC (54,316 ± 362 vs. 55,613 ± 375, P = 0.018) were lower in obese subjects. The obese had significantly higher hs‐CRP, insulin, and CIMT and lower HDL‐cholesterol. Significant bivariate associations existed between maximal NMD or NMD AUC and BMI‐group (r = ?0.492, P = 0.001 or r = ?0.383, P = 0.009), hs‐CRP (r = ?0.419, P = 0.004 or r = ?0.351, P = 0.015), and HDL‐cholesterol (r = 0.374, P = 0.01 or r = 0.270, P = 0.05). On multivariate analysis, higher BMI‐group remained as the only significant determinant of maximal NMD (r² = 0.242, β = ?0.492, P = 0.002) and NMD AUC (r² = 0.147, β = ?0.383, P = 0.023). In conclusion, arterial smooth muscle function is significantly impaired in the obese. This may be important in their increased cardiovascular risk.     

Minimal versus umbilical waist circumference measures as indicators of cardiovascular disease risk

Objective: Measures of central obesity are strongly correlated with cardiovascular disease (CVD) risk. Although waist circumference (WC) is a commonly used measure of central obesity, there is no standard measurement location. We examined two WC locations to determine which was more highly correlated with CVD risk factors and metabolic syndrome (MS). Research Methods and Procedures: WC measures were taken on 266 sedentary, overweight men and women 45 to 60 years old. Intravenous glucose tolerance tests, fasting plasma lipid analysis, and computed tomography scans were conducted. Correlational analyses followed by the Test for Equal Correlations determined whether one WC measure better correlated with the cardiovascular risk factors. Results: In women, minimal waist had higher correlation coefficients than umbilical waist for all eight variables presented. High‐density lipoprotein‐cholesterol, low‐density lipoprotein particle size, and MS score were significantly correlated with minimal waist, but not umbilical waist. For high‐density lipoprotein size and insulin sensitivity, minimal waist was a better correlate, although the difference between waist measures only approached statistical significance (p < 0.06). In men, minimal waist had a higher correlation coefficient than umbilical waist for insulin sensitivity, fasting insulin, and visceral adipose tissue. Additionally, minimal waist was significantly correlated with MS in men and umbilical waist was not. For both genders, minimal waist was more highly correlated with visceral adipose tissue than umbilical waist. Discussion: For every metabolic variable presented, minimal WC was more highly correlated with CVD risk than was umbilical WC in women. The data for women indicate that WC location is important when determining CVD risk. In men, minimal waist was better, although the data were less compelling.     

Plasma stearoyl‐CoA desaturase indices: Association with lifestyle,diet, and body composition

Objective:

Stearoyl‐coenzyme A desaturase‐1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity‐related diseases. We examined the relations of two plasma SCD activity indices (16:1n‐7/16:0, 18:1n‐9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.

Design and Methods:

This population‐based, cross‐sectional study of 2021 elderly (71–74 y) men and women from the Hordaland Health Study in Western Norway was conducted using a validated food frequency questionnaire, body composition measurements by dual‐energy X‐ray absorptiometry and determination of the plasma fatty acid profile.

Results:

In multivariate regression analyses, plasma SCD indices were positively associated with BMI and body fat (P < 0.001 for both). From the 2.5th to 97.5th percentiles of plasma SCD‐16 and SCD‐18 indices, fat mass differed by about 8 kg and 5 kg, respectively. Intake of polyunsaturated fatty acids were negatively associated with SCD‐16 (partial r = ?0.30) and SCD‐18 (partial r = ?0.24) (P < 0.001 for both). Alcohol intake was positively associated with SCD‐16 (partial r = 0.26) and SCD‐18 (partial r = 0.16) (P < 0.001 for both), whereas coffee consumption and physical activity were inversely associated with SCD‐16 (P = 0.026 and P = 0.006, respectively) and SCD‐18 (P = 0.001 and P = 0.022, respectively).

Conclusions:

In this elderly population, plasma markers of SCD1 activity are associated with increased adiposity. Furthermore, modifiable dietary habits and lifestyle are associated with plasma SCD indices. These results suggest that SCD1 activity may be a promising target for weight control.

     

Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA Study

Objective: Epidemiological studies showing an association between the melanocortin‐4‐receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators. Methods and Procedures: We analyzed this polymorphism in 7,888 adults of a population‐based cross‐sectional study applying regression‐based statistical models. Results: Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (–1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA_1c) (–0.09%, P = 0.040), and increased HDL‐cholesterol (HDL‐C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA_1c and HDL‐C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness. Discussion: Our representative study of well‐phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient‐related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.     

Lipoprotein Subpopulation Distributions in Lean,Obese, and Type 2 Diabetic Women: A Comparison of African and White Americans

Objective: Abnormal subpopulation distributions of plasma lipoproteins have been reported in white American (WA) women with obesity and type 2 diabetes that explain part of the elevated rate of cardiovascular disease in these patients. This study examined if these perturbations also occur in obese and diabetic African American (AA) women and compared the lipoprotein profiles with WA counterparts. Research Methods and Procedures: We determined the lipoprotein subpopulation distribution in the plasma of 51 lean women (29 WA, 22 AA, body mass index [BMI] < 30), 50 obese women (27 WA, 23 AA, BMI > 30), and 43 obese women with type 2 diabetes (27 WA, 16 AA), by nuclear magnetic resonance spectroscopy. Results: AA diabetic women, like WA diabetic women, had a larger average very low density lipoprotein (VLDL) size, elevated levels of small low density lipoprotein cholesterol (LDL‐C), and lower levels of small high density lipoprotein cholesterol (HDL‐C), when compared to lean controls (p < 0.05). These differences were accompanied by higher VLDL‐triglycerides (TG) and LDL‐C in WA (p < 0.05), but not in AA. Although the effects of obesity and diabetes on lipoprotein subpopulation were fairly similar for AA and WA, some racial differences, particularly with respect to HDL, were observed. Discussion: The atherogenic perturbations in lipoprotein profiles of obese AA women, particularly those with diabetes, were relatively similar to those found in WA women and may be contributing to the increased rate of cardiovascular disease (CVD) in AA with obesity and diabetes. The parameters of subpopulation distribution may provide better markers for CVD than lipid concentrations alone, particularly in AA women. Furthermore, subtle racial differences in lipoprotein profiles suggest that race‐specific criteria may be needed to screen patients for CVD.