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.     

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.     

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.     

IL-12 serum levels in patients with type 2 diabetes treated with sulphonylureas

Interleukin-12 (IL-12) has been identified as a pro-inflammatory cytokine which is thought to contribute to the development of atherosclerosis. However, to date, the various associations between factors related to the course of type 2 diabetes, like metabolic compensation, beta cell secretory dysfunction, insulin resistance and IL-12 serum levels, remain unclear. Our study involved 41 patients with type 2 diabetes, 19 patients with coronary artery disease (CAD), and 19 healthy controls. We measured serum levels of fasting glucose, HbA₁c, 1,5-anhydro-d-glucitol, and lipids. In addition, serum levels of C-peptide, insulin, proinsulin and IL-12 were assayed. HOMA_IR score was calculated. The serum concentrations of IL-12 were higher in diabetics than in either patients with CAD or healthy controls, and were correlated with BMI, C-peptide, insulin, HOMA_IR, proinsulin and HDL serum levels. Multiple regression analysis revealed that the IL-12 serum level in type 2 diabetics primarily is dependent upon fasting proinsulin concentration. Our results demonstrate that elevated IL-12 serum levels in type 2 diabetics treated with sulphonylureas are induced especially by peripheral insulin resistance and beta cells dysfunction, as expressed by fasting serum proinsulin levels. This finding gives us hope that treatment to decrease peripheral insulin resistance and to avoid excessive proinsulin secretion might be successful in the prevention of IL-12-induced atherosclerosis.     

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.     

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.     

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.     

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.     

Short-term effect of weight loss through restrictive bariatric surgery on serum levels of vaspin in morbidly obese subjects

The aims of this study were to evaluate the short-term effects of laparoscopic restrictive bariatric surgery (LRBS) on plasma levels of vaspin and the potential associations of changes in vaspin levels with changes in anthropometric indices, insulin-resistance and dietary intake. Thirty, severely obese subjects (21 female; mean age, 32.5 years) with a mean body mass index (BMI) of 44.1 ± 4.9 kg/m(2) underwent LRBS. Measurements of anthropometric indices, dietary intakes, physical activity and plasma vaspin concentrations were performed prior to, and six weeks after LRBS. Insulin-sensitivity was estimated using the homeostasis model assessment of insulin-resistance (HOMA-IR). Six weeks after LRBS, BMI decreased to a mean of 38.4 ± 4.9 kg/m(2). Significant reductions were also observed in waist circumference (WC), daily intakes of calorie, fat and protein, and plasma concentrations of triglyceride. No significant change was observed in fasting levels of insulin, blood sugar or HOMA-IR. Vaspin decreased significantly (0.26 ± 0.17 vs 0.36 ± 0.20, p=0.048) following surgery. While the percentage change of vaspin was not correlated with percent changes in anthropometric indices and HOMA-IR, it correlated positively with the percentage change in intake of calories, fat and protein: this correlation remained significant even after adjustment for sex and changes in WC and HOMA-IR. Our study suggests that LRBS decreases the serum vaspin concentrations in parallel with the restriction of dietary intake. Furthermore, decreased levels of vaspin early after LRBS seem more likely to result from decreased dietary intake rather than weight-loss-induced insulin sensitivity improvement.     

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.     

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.     

Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance

Visceral adipose fat has been claimed to be the link between obesity and insulin resistance through the released adipokines. This study aimed to assess the expression of vaspin as one of the recent adipokines in rats abdominal subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3 weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not in controls groups. In DIO group, visceral vaspin expression was higher than in that of subcutaneous fat and was positively correlated with body weight. Upregulation of visceral vaspin expression in DIO was concomitant with the development of insulin resistance (increase in fasting serum insulin and HOMA-IR) and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats, with significant improvements of insulin resistance parameters and serum leptin compared to DIO group was found. In conclusion, increased visceral vaspin expression in obesity was associated with insulin resistance. Further investigations into the molecular links between vaspin and obesity may unravel innovative therapeutic strategies in people affected by obesity-linked insulin resistance, metabolic syndrome, and type 2 diabetes.     

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.     

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.     

Increased Soluble Leptin Receptor Levels in Morbidly Obese Patients With Insulin Resistance and Nonalcoholic Fatty Liver Disease

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMA_IR) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.     

Change in Vascular Adhesion Protein‐1 and Metabolic Phenotypes after Vertical Banded Gastroplasty for Morbid Obesity

Objective: The association between circulating vascular adhesion protein‐1 (VAP‐1) and metabolic phenotypes has been shown to be inconsistent. The current study explored whether the changes in serum VAP‐1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery. Research Methods and Procedures: Clinical characteristics and serum VAP‐1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m²) were measured before and after vertical banded gastroplasty. Results: Before surgery, serum VAP‐1 levels correlated positively with fasting plasma glucose (γ = 0.56, p = 0.01) and negatively with insulin levels (γ = ?0.51, p = 0.021). After surgery, the changes in serum VAP‐1 levels were negatively correlated with the changes in waist circumference (γ = ?0.57, p = 0.011), diastolic blood pressure (DBP) (γ = ?0.56, p = 0.015), and mean arterial pressure (γ = ?0.46, p = 0.055). In multivariate regression, serum VAP‐1 levels were negatively correlated with waist circumference (β = ?2.36, p = 0.014) and DBP (β = ?3.02, p = 0.017) after adjusting for age and gender. The change in DBP was negatively correlated with the change in VAP‐1 levels after adjusting for age, gender, and steady‐state plasma glucose. Discussion: The results suggest that VAP‐1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects. After surgery, the changes in VAP‐1 levels were associated with changes in visceral adiposity and DBP. Serum VAP‐1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people.     

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.     

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.     

In Central Obesity,Weight Loss Restores Platelet Sensitivity to Nitric Oxide and Prostacyclin

Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors—guanosine 3′,5′‐cyclic monophosphate (cGMP) and adenosine 3′,5′‐cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet‐induced body‐weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6‐month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA_IR)); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD‐40 ligand (sCD‐40L) and soluble P‐selectin (sP‐selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8‐bromoguanosine 3′,5′‐cyclic monophosphate (8‐Br‐cGMP) and 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐Br‐cAMP) to reduce platelet aggregation in response to adenosine‐5‐diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body‐weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8‐Br‐cGMP, and 8‐Br‐cAMP to reduce ADP‐induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body‐weight target. Changes of platelet function correlated with changes of HOMA_IR. Thus, in central obesity, diet‐induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity.     

Are Elevated Aminotransferases and Decreased Bilirubin Additional Characteristics of the Metabolic Syndrome?

Abnormal liver tests, as well as morphological changes in the liver, are frequent among obese patients. Other frequent disturbances are visceral fat accumulation, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertriglyceridemia, and hypertension; these are a set of aberrations known as the metabolic syndrome. In order to investigate a possible relationship between the metabolic syndrome and impaired liver status we examined associations between liver tests, metabolic variables (insulin, glucose, and triglycerids), body composition and nutrition in 1083 men (BMI 28.8–63.8 kg/m²) and 1367 women (BMI 26.7–68.0 kg/m²) in the ongoing intervention study of Swedish Obese Subjects (SOS). Standard biochemical techniques were used to assess liver status and metabolic variables. Lean body mass (LBM) and masses of visceral and subcutaneous adipose tissue (AT) were estimated by means of computed tomography (CT) calibrated anthropometric equations. In both genders aspartate aminotransferase and alanine aminotransferase were, or tended to be, positively correlated to fasting serum insulin, visceral AT (women), and alcohol intake. In women, the aminotransferases were also correlated with fasting blood glucose. In both genders alkaline phosphatase was, or tended to be, positively associated with visceral AT, insulin (women), and glucose. Bilirubin was negatively correlated to insulin and visceral AT in men and women. Additional multivariate analyses indicated that alcohol had less explanatory power than serum insulin for the examined liver tests, especially among women. These results suggest that pathological liver tests in the obese may represent an expression of the metabolic syndrome.