Association of Long‐term Change in Waist Circumference With Insulin Resistance

Recent studies have shown that fat accumulation is associated with insulin resistance; however, the risks associated with long‐term changes and fluctuations in central fatness are less clear. This study examined the longitudinal relationship between waist circumference (WC) and insulin resistance using three dimensions of WC: baseline WC, slope of linear changes in WC, and fluctuation of WC around the slope during 20 years of follow‐up. Anthropometry, insulin resistance (homeostasis model assessment (HOMA_IR)), and lifestyle factors were obtained in a population‐based, prospective observational study (Coronary Artery Risk Development in Young Adults (CARDIA)) during 1985–2006, excluding participants who had been diagnosed with diabetes at any examination. After adjusting for socio‐demographic and lifestyle factors, the evolution of HOMA_IR from CARDIA year 15 to 20 was 6.9% higher per standard deviation of year 0 WC (P trend <0.0001) and 6.3% higher per standard deviation increase in the change in WC over the long term (P trend <0.0001). However, WC fluctuations around the linear change were not associated with insulin resistance or its evolution. The level of HOMA_IR increased substantially with steeper linear WC slope among initially thinner participants at baseline, whereas this association tended to be weaker in those with higher initial WC (P interaction <0.0001). We conclude that year 0 WC and long‐term increment in WC are associated with worsening insulin resistance. However, the association of HOMA_IR with slope of WC change may vary across the range of initial WC.     

Adipokines,Ghrelin and Obesity‐Associated Insulin Resistance in Nondiabetic Patients with Acute Coronary Syndrome

Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity‐related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA_IR)‐insulin resistance index, plasma adiponectin, leptin, total (T‐Ghrelin), acylated (Acyl‐Ghrelin), and desacylated ghrelin (Desacyl‐Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non‐ACS, ACS patients had similar HOMA_IR and plasma adipokines, but lower T‐ and Desacyl‐Ghrelin and higher Acyl‐Ghrelin. Obesity (BMI > 30) was associated with higher HOMA_IR, lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non‐ACS subjects. In ACS (n = 60) HOMA_IR remained associated negatively with adiponectin and positively with leptin independently of BMI and c‐reactive protein (CRP) (P < 0.05). On the other hand, low T‐ and Desacyl‐Ghrelin with high Acyl‐Ghrelin characterized both obese and non‐obese ACS patients and were not associated with HOMA_IR. In conclusion, in ACS patients, obesity and obesity‐related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.     

Insulin Resistance and Oxidative Stress Influence Colony‐Forming Unit‐Endothelial Cells Capacity in Obese Patients

The aim of this study was to investigate the relationship between a sub‐population of endothelial progenitor cells (EPC), namely colony‐forming unit‐endothelial cells (CFU‐EC), their colony‐forming capacity and variable clinical parameters, including insulin resistance and oxidative stress, in obese individuals. Thirty‐eight obese adults (aged 42.5 ± 12.7), with BMI 32.3 ± 4.0 and 13 normal‐weight controls (aged 48.2 ± 12.9; BMI 23.2 ± 2.3) were studied. CFU‐EC colony‐forming capacity was impaired in the group of obese individuals compared to the normal‐weight controls (P = 0.001). The inverse correlation between homeostasis model assessment‐insulin resistance (HOMA_IR) index and CFU‐EC number (r = ?0.558, P < 0.0001) as well as positive total antioxidant status of plasma (TAS)/CFU‐EC relation were noticed during the study. Additionally, correlations between the concentration of triglycerides (TG), high‐density lipoproteins (HDLs), and body composition parameters in the obese participants were established. Our results demonstrate that insulin resistance and oxidative stress have a significant impact on the CFU‐EC colony formation in obesity. Moreover, in multivariate regression analysis, in both studied groups, the HOMA_IR index and HDL concentration were independent predictors of the number of CFU‐EC. Endothelium dysfunction, which can be present in obesity, may in part be caused by EPC function impairment in this condition.     

Independent Associations Between Cardiorespiratory Fitness and Abdominal Obesity With Metabolic Risk in Adolescents and Adults

Our objective was to examine the independent association between abdominal obesity (waist circumference (WC)) and cardiorespiratory fitness (CRF) with metabolic syndrome (MetS) in 2,197 adults (ages 20–49 years) and 3,223 adolescents (ages 12–19 years). Individuals were stratified by CRF and WC using sex‐ and age‐specific MetS criteria for adolescents and adults. Adolescents had a lower prevalence rate of MetS (5.4% vs. 12.8%) and high WC (15.5% vs. 35.7%), but a higher prevalence rate of low CRF (37.6% vs. 15.9%) than adults. As compared to adolescents and adults with low WC, those with a high WC (odds ratio (OR) = 5.5–16.5, P < 0.001) were more likely to have a clustering of MetS factors than those with low WC (OR = 1.2–3.8, P = 0.3 to <0.001), regardless of fitness level. Conversely, the beneficial effects of having moderate/high CRF on MetS were only observed in individuals with low WC, and not high WC. Thus, in conclusion, both high WC and low CRF are associated with increased odds of MetS in adolescents and adults. However, increased abdominal obesity is more strongly associated with MetS in adolescents and adults.     

Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin Resistance in the Framingham Heart Study

Insulin resistance is associated with central obesity and an increased risk of cardiovascular disease. Our objective is to examine the association between abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to determine which fat depot is a stronger correlate of insulin resistance, and to assess whether there was an interaction between SAT, VAT, and age, sex, or BMI. Participants without diabetes from the Framingham Heart Study (FHS), who underwent multidetector computed tomography to assess SAT and VAT (n = 3,093; 48% women; mean age 50.4 years; mean BMI 27.6 kg/m²), were evaluated. Insulin resistance was measured using the homeostasis model and defined as HOMA_IR ≥75th percentile. Logistic regression models, adjusted for age, sex, smoking, alcohol, menopausal status, and hormone replacement therapy use, were used to assess the association between fat measures and insulin resistance. The odds ratio (OR) for insulin resistance per standard deviation increase in SAT was 2.5 (95% confidence interval (CI): 2.2–2.7; P < 0.0001), whereas the OR for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI: 3.1–3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI: 1.9–2.5; P < 0.0001). We observed an interaction between VAT and BMI for insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and HOMA_IR (P interaction = 0.003), where VAT had a stronger association in obese individuals. In conclusion, SAT and VAT are both correlates of insulin resistance; however, VAT is a stronger correlate of insulin resistance than SAT.     

Appetite‐Regulating Hormone Changes in Patients With Craniopharyngioma

Patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, often suffer from uncontrolled eating and severe obesity. We aimed to compare peripherally secreted hormones involved in controlling food intake in normal weight and obese children and adolescents with CP vs. controls. Plasma insulin, glucose, total ghrelin, and peptide‐YY (PYY) levels were assessed under fasting conditions as well as 60 min after liquid mixed meal in four groups: Normal weight (n = 12) and obese (n = 15) CP patients, and 12 normal weight and 15 obese otherwise healthy BMI‐, gender‐ and age‐matched controls. Homeostasis model assessment of insulin resistance (HOMA_IR), as well as quantitative insulin sensitivity check index (QUICKI) were calculated. Obese CP subjects had significantly higher HOMA_IR, higher baseline and postmeal insulin but lower ghrelin levels, weaker postmeal changes for PYY, and lower QUICKI compared to obese controls. QUICKI data from all CP patients correlated positively with ghrelin and PYY % postmeal changes (ghrelin: r = 0.38, P = 0.023; PYY r = 0.40, P = 0.017) and negatively with standard deviation score‐BMI (SDS‐BMI: r = ?0.49, P = 0.002). Tumor growth of 87% obese and 58% of normal weight CP patients affected the hypothalamic area which was associated with higher SDS‐BMI and weaker % postmeal ghrelin changes (P = 0.014) compared to CP patients without hypothalamic tumor involvement. Blunted postmeal ghrelin and PYY responses in obese CP subjects are likely due to their higher degree of insulin resistance and lower insulin sensitivity compared to matched obese controls. Thus, insulin resistance in CP patients seems to affect eating behavior by affecting meal responses of gut peptides.     

Early Detrimental Metabolic Outcomes of rs17300539‐A Allele of ADIPOQ Gene Despite Higher Adiponectinemia

Minor allele A of single‐nucleotide polymorphism (SNP) 11391 G/A of ADIPOQ gene (rs17300539) has been consistently associated with higher adiponectin levels in adults and children. The aim of this study was to investigate the metabolic role of this variant in a large cohort of children of European origin. A total of 1,852 children from two general populations in Verona and in Fleurbaix–Laventie and from the Lille childhood obesity cohort, were genotyped and pooled together after checking for the absence of genetic heterogeneity for rs17300539 between Italian and French children. The genotype of rs17300539 was studied in relation to circulating adiponectin levels, BMI, fasting plasma glucose, fasting serum insulin (FSI), insulin resistance index (homeostasis model assessment of insulin resistance (HOMA_IR)), high‐density lipoprotein cholesterol, and triglycerides. After adjustment for known confounders, rs17300539 GA+AA carriers had 1.6 µg/ml higher adiponectin levels (P = 6 × 10^?8) than GG carriers. They also showed higher BMI (B = 0.97, P = 0.015) and higher prevalence of obesity (OR = 1.35 (1.06–1.85), P = 0.015) than GG carriers. Before adjusting for obesity status, GA+AA carriers had higher FSI (B = 1.10, P = 0.040) and higher HOMA_IR (B = 0.31, P = 0.020) than GG carriers. After adjustment for obesity status, they did not differ from GG carriers for any metabolic parameter, either among obese or nonobese children. The rs17300539‐A variant, though consistently associated with higher adiponectin levels, does not exert any appreciable protective metabolic effect in children, either in the presence or absence of obesity. In contrast, this SNP may increase the risk for childhood obesity and related insulin resistance.     

Effects of Weight Reduction on Serum Vaspin Concentrations in Obese Subjects: Modification by Insulin Resistance

Visceral adipose tissue‐derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12‐week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMA_IR). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMA_IR group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMA_IR group was positively correlated with change in BMI and negatively correlated with initial HOMA_IR level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMA_IR group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.     

Relationships Among Obesity,Inflammation, and Insulin Resistance in African Americans and West Africans

Several research studies in different populations indicate that inflammation may be the link between obesity and insulin resistance (IR). However, this relationship has not been adequately explored among African Americans, an ethnic group with disproportionately high rates of obesity and IR. In this study, we conducted a comparative study of the relationship among adiposity, inflammation, and IR in African Americans and West Africans, the ancestral source population for African Americans. The associations between obesity markers (BMI and waist‐to‐hip ratio (WHR)), inflammatory markers (high‐sensitivity C‐reactive protein (hsCRP), haptoglobin, interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α), and IR (homeostasis model assessment of insulin resistance (HOMA_IR)) were evaluated in 247 West Africans and 315 African Americans. In average, African Americans were heavier than the West Africans (by an average of 1.6 BMI units for women and 3 BMI units for men). Plasma hsCRP, haptoglobin, and IL‐6 (but not TNF‐α level) were higher in African Americans than in West Africans. In both populations, BMI was associated with markers of inflammation and with HOMA_IR, and these associations remained significant after adjusting for sex and age. However, the pattern of associations between measured inflammatory markers and IR was different between the two groups. In West Africans, hsCRP was the only inflammatory marker associated with IR. In contrast, hsCRP, haptoglobin, and IL‐6 were all associated with IR in African Americans. Interestingly, none of the associations between markers of inflammation and IR remained significant after adjusting for BMI. This finding suggests that in African Americans, the relationship between inflammatory markers and IR is mediated by adiposity.     

Association of Pericardial Fat With Liver Fat and Insulin Sensitivity After Diet‐Induced Weight Loss in Overweight Women

Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity‐related insulin resistance. Because PAT is a well‐known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2–46.8 kg/m², 22–41 years) followed a 14.2 ± 4‐weeks low‐calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual‐energy X‐ray absorptiometry and intrahepatocellular lipids (IHCL) by (¹)H‐magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA_IR) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA_IR (r = 0.46), and M value (r = ?0.40; all P < 0.05). During intervention, body weight decreased by ?8.5%, accompanied by decreases of ?12% PAT, ?13% VAT, ?44% IHCL, ?10% HOMA2‐%B, and +24% as well as +15% increases in HOMA2‐%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = ?0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA_IR and HOMA2‐%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross‐sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.     

Consequences of obstructive sleep apnea on metabolic profile: A Population‐Based Survey

Objective:

Epidemiologic studies that control for potential confounders are needed to assess the independent associations of obstructive sleep apnea (OSA) with metabolic abnormalities. The aim of our study was to evaluate the associations of OSA with metabolic abnormalities among the adult population of Sao Paulo, Brazil.

Design and Methods:

Questionnaires were applied face‐to‐face, full night polysomnography (PSG) was performed, and blood samples were collected in a population‐based survey in Sao Paulo, Brazil, adopting a probabilistic three‐stage cluster sample method. The metabolic profile included fasting glucose, insulin, and lipid levels. The hepatic insulin resistance index was assessed by the homeostasis model assessment‐estimated insulin resistance (HOMA_IR).

Results:

A total of 1,042 volunteers underwent PSG. Mild OSA and moderate to severe OSA comprised 21.2% and 16.7% of the population, respectively. Subjects with severe to moderate OSA were older, more obese, had higher fasting glucose, HOMA_IR, and triglycerides (TG) levels than did the mild and non‐OSA group (P < 0.001). Multivariate regression analyses showed that an apnea‐hypopnea index (AHI) ≥15 and a time of oxy‐hemoglobin saturation <90% were independently associated with impaired fasting glucose, elevated TG, and HOMA_IR.

Conclusions:

The results of this large cross‐sectional epidemiological study showed that the associations of OSA and metabolic abnormalities were independent of other risk factors.     

BMI and Metabolic Profile in Patients With Prolactinoma Before and After Treatment With Dopamine Agonists

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty‐two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low‐density lipoprotein (LDL)‐cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA_IR) index, glucose, LDL‐cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.     

Obesity and Persistent Organic Pollutants: Possible Obesogenic Effect of Organochlorine Pesticides and Polychlorinated Biphenyls

Persistent organic pollutants (POPs) are endocrine‐disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross‐sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro‐diphenyl‐dichloroethylene (pp‐DDE), and β‐hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMA_IR). βHCH correlated significantly positively with HOMA_IR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMA_IR, whereas serum PCB levels were inversely correlated with BMI and HOMA_IR. Combined, these results suggest that the diabetogenic effect of low‐dose exposure to POPs might be more complicated than a simple obesogenic effect.     

Common PCSK1 Haplotypes Are Associated With Obesity in the Chinese Population

Prohormone convertase subtilisin/kexin type 1 (PCSK1) genetic polymorphisms have recently been associated with obesity in European populations. This study aimed to examine whether common PCSK1 genetic variation is associated with obesity and related metabolic phenotypes in the Chinese population. We genotyped nine common tag single‐nucleotide polymorphisms (tagSNP) of the PCSK1 gene in 1,094 subjects of Chinese origin from the Stanford Asia‐Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. One SNP in the PCSK1 gene (rs155971) were nominally associated with risk of obesity in the SAPPHIRe cohort (P = 0.01). A common protective haplotype was associated with reduced risk of obesity (23.79% vs. 32.89%, P = 0.01) and smaller waist circumference (81.71 ± 10.22 vs. 84.75 ± 10.48 cm, P = 0.02). Another common haplotype was significantly associated with increased risk of obesity (37.07% vs. 23.84%, P = 0.005). The global P value for haplotype association with obesity was 0.02. We also identified a suggestive association of another PCSK1 SNP (rs3811951) with fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA_IR), triglycerides, and high‐density lipoprotein cholesterol (P = 0.05, 0.003, 0.001, 0.04, and 0.04, respectively). These data indicate common PCSK1 genetic variants are associated with obesity in the Chinese population.     

Obesity and body fat classification in the metabolic syndrome: Impact on cardiometabolic risk metabotype

Objective:

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study).

Design and Methods:

Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n‐3 polyunsaturated fatty acids (LC n‐3 PUFAs)).

Results:

About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥30 kg/m²) and BF% (≥25% (men) and ≥35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor‐1 (PAI‐1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA‐IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor‐α (TNF‐α) concentrations were lower post‐intervention in NOO individuals compared with OO subjects (P < 0.001).

Conclusions:

In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.     

Evaluation of Oxidative Stress in Overweight Subjects With or Without Metabolic Syndrome

Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross‐sectional study. The control group included 50 healthy individuals with a BMI between 20 and 24.9 kg/m² and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m². Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation‐xylenol orange assay compared to overweight subjects without MetS (P < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (P < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.     

Effect of Family History of Type 2 Diabetes on White Blood Cell Count in Adult Women

Objective: To evaluate the effect of a first‐degree family history of type 2 diabetes on white blood cell (WBC) count, a risk factor for atherosclerotic vascular disease, in glucose‐tolerant adult women Research Methods and Procedures: WBC count was measured in 174 normal weight, overweight, and obese female offspring of type 2 diabetic patients (FH⁺) and 174 age‐ and BMI‐matched female controls with no family history of type 2 diabetes (FH^?). Other measurements included fat mass (FM), measured by body impedance analysis; central fat accumulation, evaluated by waist circumference; insulin resistance, estimated by homeostatic model assessment for insulin resistance (HOMA_IR); systolic and diastolic blood pressure; and fasting concentrations of glucose, insulin, and lipids. Results: WBC count, waist circumference, systolic blood pressure, and fasting levels of glucose, insulin, and triglycerides were significantly higher in FH⁺ than in FH^? subjects. In FH⁺ individuals, WBC count was positively associated with BMI, FM, waist circumference, HOMA_IR, and triglyceride and insulin concentrations, and negatively correlated with age and high‐density lipoprotein‐cholesterol. In FH^? subjects, WBC count was directly associated with BMI, FM, waist circumference, and triglyceride and insulin concentrations, and inversely correlated with age and high‐density lipoprotein‐cholesterol. After multivariate analyses, WBC count maintained a significant association with age, systolic blood pressure, and HOMA_IR in FH⁺ subjects and with age, BMI, FM, and triglycerides in FH^? individuals. Discussion: This study indicates that WBC count is increased in adult women with genetic predisposition to type 2 diabetes, and its main correlates are insulin resistance in FH⁺ and adiposity in FH^? individuals.     

Effect of Glucose Tolerance Status on PAI‐1 Plasma Levels in Overweight and Obese Subjects

Objective: The aim of our study was to examine whether plasminogen activator inhibitor‐1 (PAI‐1) plasma levels varied as a function of differences in glucose tolerance status independently of body fatness, body‐fat distribution, and insulin sensitivity. Research Methods and Procedures: Plasma PAI‐1 antigen levels, along with insulin resistance [measured by homeostatic model assessment (HOMA_IR)], central fat accumulation, body composition, blood pressure, and fasting concentrations of glucose, insulin, and lipids, were measured in 229 overweight and obese [body mass index (BMI) ≥25 kg/m²) subjects with normal glucose tolerance (NGT) and in 44 age‐ and BMI‐matched subjects with impaired glucose tolerance (IGT). Results: Plasma PAI‐1 antigen levels were significantly higher in IGT than in NGT subjects. Log PAI‐1 was positively correlated with BMI, HOMA_IR, and log insulin, and inversely associated with high‐density lipoprotein‐cholesterol both in IGT and in NGT individuals. On the other hand, log PAI‐1 was positively correlated with waist circumference, fat mass (FM), fat‐free mass, systolic and diastolic blood pressure, and log triglycerides only in the NGT group. After multivariate analyses, the strongest determinants of PAI‐1 levels were BMI, FM, waist circumference, and high‐density lipoprotein cholesterol in the NGT group and only HOMA_IR in the IGT cohort. Discussion: This study demonstrates that PAI‐1 concentrations are higher in IGT than in NGT subjects. Furthermore, we suggest that the influences of total adiposity, central fat, and insulin resistance, main determinants of PAI‐1 concentrations, are different according to the degree of glucose tolerance.     

Clinical Utility of Waist Circumference in Predicting All‐cause Mortality in a Preventive Cardiology Clinic Population: A PreCIS Database Study

Although obesity is a risk factor for mortality, it is unclear whether waist circumference (WC) is a better predictor of mortality than BMI in a clinical setting of patients at high risk for coronary artery disease (CAD). Thus, we compared the association between WC and BMI with all‐cause mortality in relation to traditional CAD risk factors in a high‐risk cohort. Study population included 5,453 consecutive new patients seen between 1996 and 2005 for management of CAD risk factors in a preventive cardiology clinic. Mortality was determined from the Social Security Death Index. There were 359 deaths over a median follow‐up of 5.2 years. Mortality was greater in high (>102 cm in men and >88 cm in women) vs. normal WC in both genders (P < 0.01). The unadjusted Cox proportional hazard ratio (HR) for continuous WC (per cm) was 1.02 (P < 0.001) in both genders and remained significant after adjustment for CAD risk factors (HR = 1.01 in men, HR = 1.03 in women, both P < 0.05). BMI did not associate statistically with mortality. WC associated with diabetes mellitus (DM) and CAD prevalence (P < 0.001). BMI associated only with DM (P < 0.001) and this association disappeared when WC was added to the model. We conclude that WC is an independent predictor of all‐cause mortality in a preventive cardiology population. These data affirm the clinical importance of WC measurements for mortality, DM, and CAD risk prediction and suggest that obesity‐specific interventions targeting WC in addition to traditional risk factor management may favorably impact these outcomes.     

Metabolic syndrome is not a risk factor for kidney dysfunction in obese non-diabetic subjects

Objective: To investigate whether insulin resistance (IR) and the metabolic syndrome (MS) are associated with kidney dysfunction in obese non‐diabetic (OND) subjects. Methods and Procedures: Three‐hundred and eighty (113M/267F; age = 41 ± 14 years) OND subjects (BMI ≥ 30 kg/m²; range = 43 ± 8 kg/m²) were studied. Anthropometric measures, blood pressure, fasting glucose, insulin, lipid profile, and serum creatinine were evaluated. Glomerular filtration rate (GFR) was estimated (e‐GFR) with the Modification of Diet in Renal Disease equation. Chronic kidney disease (CKD) was defined as e‐GFR <60 ml/min/1.73 m². Results: e‐GFR was associated with gender (being lower in women) (P = 0.001) and age (P < 0.0001). CKD was present in 32 subjects (8.4%), who were older (P < 0.0001) and more frequently affected by hypertension (P = 0.04) as compared to subjects without CKD. MS was present in 212 (55.8%) subjects. They were older (P< 0.001), had lower e‐GFR (P = 0.02) and were more frequently affected by CKD (odds ratio (OR), 95% confidence interval (CI) = 2.3, 1.1–5.1) than those without MS. However, differences in e‐GFR values and in the risk of CKD were no longer statistically significant after adjusting for age (P = 0.99 for e‐GFR and OR, 95% CI = 1.2, 0.5–2.8 for the risk of CKD, respectively). Homeostasis model assessment of IR (HOMA_IR) index was neither higher in subject with CKD (P = 0.1) nor inversely correlated with e‐GFR (r = 0.1, P = 0.1). Discussion: In OND individuals the risk of CKD is independent of the MS and related abnormalities. This suggests that these individuals are not susceptible to a further deleterious role on kidney function on the top of that played by obesity itself.