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 is the Best Predictor of the Metabolic Syndrome in Subjects With a First‐Degree Relative With Type 2 Diabetes

Although obesity is associated with insulin resistance and the metabolic syndrome (MetS), some obese individuals are metabolically healthy. Conversely, some lean individuals are insulin resistant (IR) and at increased cardiometabolic risk. To determine the relative importance of insulin sensitivity, BMI and waist circumference (WC) in predicting MetS, we studied these two extreme groups in a high‐risk population. One thousand seven hundred and sixty six subjects with a first‐degree relative with type 2 diabetes were stratified by BMI and homeostasis model assessment of insulin resistance (HOMA_IR) into groups. IR groups had higher triglycerides, fasting glucose, and more diabetes than their BMI‐group insulin sensitive (IS) counterparts. Within both IS and IR groups, obesity was associated with higher HOMA_IR and diastolic blood pressure (BP), but no difference in other metabolic variables. MetS (Adult Treatment Panel III (ATPIII)) prevalence was higher in IR groups (P < 0.001) and more subjects met each MetS criterion (P < 0.001). Within each BMI category, HOMA_IR independently predicted MetS (P < 0.001) whereas WC did not. Within IS and IR groups, age and WC, but not BMI, were independent determinants of MetS (P < 0.001). WC was a less meaningful predictor of MetS at higher values of HOMA_IR. HOMA_IR was a better predictor of MetS than WC or BMI (receiver operating characteristic (ROC) area under the curve 0.76 vs. 0.65 vs. 0.59, P < 0.001). In conclusion, insulin sensitivity rather than obesity is the major predictor of MetS and is better than WC at identifying obese individuals with a healthier metabolic profile. Further, as many lean individuals with a first‐degree relative with type 2 diabetes are IR and metabolically unhealthy, they may all benefit from metabolic testing.     

Sphingolipid Content of Human Adipose Tissue: Relationship to Adiponectin and Insulin Resistance

Ceramides (Cer) are implicated in obesity‐associated skeletal muscle and perhaps adipocyte insulin resistance. We examined whether the sphingolipid content of human subcutaneous adipose tissue and plasma varies by obesity and sex as well as the relationship between ceramide content and metabolic indices. Abdominal subcutaneous adipose biopsies were performed on 12 lean adults (males = 6), 12 obese adults (males = 6) for measurement of sphingolipid content and activity of the main ceramide metabolism enzymes. Blood was sampled for glucose, insulin (to calculate homeostasis model assessment‐estimated insulin resistance (HOMA_IR)) adiponectin, and interleukin‐6 (IL‐6) concentrations. Compared to lean controls, total ceramide content (pg/adipocyte) was increased by 31% (P < 0.05) and 34% (P < 0.05) in obese females and males, respectively. In adipocytes from obese adults sphingosine, sphinganine, sphingosine‐1‐phosphate, C14‐Cer, C16‐Cer, and C24‐Cer were all increased. C18:1‐Cer was increased in obese males and C24:1‐Cer in obese females. For women only, there was a negative correlation between C16‐Cer ceramide and plasma adiponectin (r = ?0.77, P = 0.003) and a positive correlation between total ceramide content and HOMA_IR (r = 0.74, P = 0.006). For men only there were significant (at least P < 0.05), positive correlations between adipocyte Cer‐containing saturated fatty acid and plasma IL‐6 concentration. We conclude that the sexual dimorphism in adipose tissue behavior in humans extends to adipose tissue sphingolipid content its association with adiponectin, IL‐6 and insulin resistance.     

Fasting Plasma Glucose (FPG) and the Risk of Impaired Glucose Tolerance in Obese Children and Adolescents

A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity. The oral glucose tolerance test (OGTT), the gold standard to diagnose this condition, may not be realistically performed in all patients due to discomfort, labor, and cost. The aim of this study was to assess whether one or more biochemical indexes measured in fasting conditions could be used to identify obese children at risk of IGT. A cohort of 563 white obese children and adolescents (M/F: 315/248; aged 4–17 years) was recruited and underwent anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of insulin resistance (HOMA_IR) were tested in pursuit of a possible threshold to be used as a predictor of IGT. Thirty‐seven children (6.9%) had IGT and one child (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA_IR were all significantly higher in children with IGT than in children without IGT. Receiver‐operating characteristic (ROC) curve analyses run for gender and puberty‐adjusted FPG, FSI, and HOMA_IR were all significant: area under the curve (95% confidence interval) equaled 0.68 (0.59–0.76), 0.66 (0.56–0.76), and 0.68 (0.59–0.78), respectively. The three parameters did not show significantly different sensitivity/specificity in the pooled population or in the gender/puberty subgroups. Thresholds varied among gender/puberty subgroups for FSI and HOMA_IR, but not for FPG, which showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG may be considered a screening tool to narrow clinical indication to OGTT in obese white children and adolescents.     

Variants in the Adiponectin Gene and Serum Adiponectin: The Coronary Artery Development in Young Adults (CARDIA) Study

Circulating adiponectin is involved in the atherosclerotic process and has been associated with cardiovascular disease as well as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The adiponectin gene (ADIPOQ) encodes the circulating protein adiponectin and affects its expression. Only a small proportion of all known ADIPOQ polymorphisms have been investigated in relation to circulating adiponectin concentrations. Using data from 3,355 African‐American and white men and women aged 33–45 at the year 15 examination from the Coronary Artery Development in Young Adults (CARDIA) Study the association between 10 single‐nucleotide polymorphisms (SNPs) within ADIPOQ and serum adiponectin was examined using linear regression. SNPs were chosen based on a tagSNP approach. Models were stratified by self‐reported race to control for population stratification, and Bonferroni corrected for multiple comparisons. ADIPOQ SNPs rs17300539 (P < 0.0001), rs182052 (P = 0.0013), rs822393 (P = 0.0005), rs9882205 (P = 0.0001), and rs3774261 (P = 0.0001) were strongly associated with serum adiponectin concentrations in whites. In general, there was a dose‐response relationship of adjusted mean adiponectin concentrations across genotypes. Only one SNP, rs17300539 was marginally associated with serum adiponectin concentrations (P = 0.0087) in African Americans. Significant interactions were found between waist and rs182052 (P = 0.0029) and between rs9882505 and smoking (P = 0.001) in whites. Many ADIPOQ SNPs have not yet been examined, and additional studies are needed to determine whether these may be functional variants.     

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.     

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.     

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: Family-based study

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value = 0.001), waist circumference (p-value = 0.037), BMI (p-value = 0.015) and percentage of total body fat (p-value = 0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.     

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.     

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.     

Decreased Liver Fatty Acid Δ‐6 and Δ‐5 Desaturase Activity in Obese Patients

Steatosis in obese nonalcoholic fatty liver disease (NAFLD) patients is a clinicopathological condition associated with depletion of n‐3 polyunsaturated fatty acids (PUFA), a feature that may be related to PUFA desaturation. Liver Δ‐6 and Δ‐5 desaturase (Δ‐6D and Δ‐5D) activities, homeostasis model assessment of insulin resistance (HOMA_IR), and ferric reducing ability of plasma (FRAP) were evaluated in 13 obese patients who underwent subtotal gastrectomy with gastro‐jejunal anastomosis in Roux‐en‐Y and 15 nonobese patients who underwent laparoscopic cholecystectomy (controls). Liver Δ‐6D and Δ‐5D activities in obese patients were 87% and 66% lower than controls (P < 0.001), respectively, with a 62% diminution in the Δ‐6D/Δ‐5D activity ratio (P < 0.02). Δ‐6D inversely correlated with both HOMA_IR (r = ?0.70, P < 0.0001) and oxidative stress assessed as the reciprocal value of FRAP (r = ?0.40, P < 0.05). Δ‐5D negatively correlated with HOMA_IR (r = ?0.48, P < 0.01) but not with FRAP^?1 (r = ?0.13, not significant). In conclusion, liver PUFA desaturation is diminished in obese NAFLD patients, in association with underlying insulin resistance and oxidative stress, which may play a role in altering lipid metabolism favoring fatty infiltration.     

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.     

ADIPOQ Polymorphisms,Monounsaturated Fatty Acids,and Obesity Risk: The GOLDN Study

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single‐nucleotide polymorphisms (SNPs), ?11377C>G and ?11391G>A, on metabolic‐related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the ?11391A allele (P = 0.001) but lower for the ?11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the ?11391G>A SNP. Carriers of the ?11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the ?11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P‐interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (≥13% of energy intake), ?11391A carriers had lower BMI (27.1 kg/m² for GA+AA vs. 29.1 kg/m² for GG, P = 0.002) and decreased obesity risk (odds ratio for ?11391A = 0.52, 95% confidence interval (CI); 0.28–0.96; P = 0.031). However, we did not detect genotype‐related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the ?11391G>A SNPs and obesity‐related traits and the potential to moderate such effects using dietary modification.     

Association of RBP4 Gene Variants and Serum HDL Cholesterol Levels in the Newfoundland Population

Retinol‐binding protein 4 (RBP4) is a novel adipokine that likely contributes to systemic insulin resistance and dyslipidemia. The role of genetic variations in RBP4 on phenotypes of glucose and lipid metabolism is not clear in humans. The purpose of this study was to examine five single‐nucleotide polymorphisms (SNPs) in the RBP4 gene to determine their relationship with markers of insulin resistance and serum lipids in the CODING Study. The CODING Study consists of 1,836 subjects recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA_IR), HOMA for β cell function (HOMA_β), total cholesterol (Chol), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and triglycerides were determined after a 12‐h fast. Five SNPs within RBP4 (rs3758539, G/A 5′ flanking region; rs61461737, A/G intron; rs10882280, C/A intron; rs11187545, A/G intron; and rs12265684, C/G intron) were genotyped using TaqMan validated or functionally tested SNP genotyping assays. After correcting for multiple testing, we observed a significant association between the minor allele of two noncoding SNPs (rs10882280 and rs11187545) and higher serum HDL‐C (P = 0.043 and 0.042, respectively). No significant associations were observed with any other parameter related to lipid metabolism. We also found no significant association between any variant sites and markers of insulin resistance. Our results suggest that genetic variations in RBP4 may play a role in the differences in serum HDL‐C levels in the NL population.     

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.     

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.     

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.     

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.     

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.     

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.