Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.

OBJECTIVE -The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. The prevalence of glucose intolerance and its determinants and the relation of cardiovascular risk factors with levels of glycemia and degree of obesity were studied in grossly obese children of European origin. RESEARCH DESIGN AND METHODS-A total of 710 grossly obese Italian children (SD score [SDS] of BMI 3.8 Ϯ 0.7) aged 6 -18 years, including 345 male subjects, underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and uric acid were measured. The 2-h postload glucose and degree of obesity, calculated as the SDS of weight/height 2 , were used as dependent variables.RESULTS -The prevalence of glucose intolerance was 4.5%. Insulin resistance (P Ͻ 0.0001), impaired insulin secretion (P Ͻ 0.0001), and diastolic blood pressure (BP) (P Ͻ 0.05) were significantly and independently related to 2-h postload glucose values. The degree of obesity did not relate to insulin resistance but was independently correlated with inflammatory proteins, uric acid, and systolic BP, variables that were often abnormal in this population.CONCLUSIONS -In these grossly obese children, both insulin resistance and impaired insulin secretion contribute to the elevation of glycemia, and the degree of obesity is related to cardiovascular risk factors independently of insulin resistance.

OBJECTIVE: The aim of this study was to evaluate liver steatosis in prepubertal and pubertal obese and the correlations with the lipid pro®le, the serum levels of hepatic parameters and the glycemic and insulinemic responses to an oral glucose tolerance test. SUBJECTS: 375 obese, 205 males and 170 females, Tanner pubertal stage I (n 82), stages II ± III (n 80) and stages IV ± V (n 213). MEASUREMENTS: Body mass index (BMI), waist ± hip ratio (WHR), total cholesterol and high density lipoprotein (HDL), cholesterolaHDL ratio, low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides (TGL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gGT, glycemia (G), insulinemia (IRI), fasting IRIaG ratio (FIGR), glycemic (mean blood glucose, MBG) and insulinemic (mean serum insulin, MSI) responses during a 120 min oral glucose tolerance test (OGTT), expressed as area under the curve (AUC)a120 min, pancreatic insulinemic response to glucose (IRG), and liver ultrasound scanning for assessing the degree of steatosis (moderate, severe). RESULTS: Liver steatosis was found in 33% of subjects in Tanner pubertal stage I, 36% in stage II ± III and 47% in stages IV ± V. BMI and transaminases were correlated with the degree of steatosis in all pubertal stages. AST, ALT and gGT were higher in the presence of steatosis, while elevated TGL was present in late puberty only; however the increase of ALT is speci®c for steatosis. CONCLUSION: Juvenile obesity involves a high risk of liver steatosis associated with alterations of transaminases and lipid but not glucose metabolism. These changes are apparent even to the prepubertal stage.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

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ContextThe last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance.ObjectivesTo assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism.SettingTertiary care centre.Patients524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender.ResultsThe prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = −0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as independent variables, showed that vitamin D was capable of predicting HbA1c levels (β = −0.101, p < 0.05).ConclusionsGiven the inherent effect of obesity on vitamin D and glucose homeostasis, current data suggest a potential independent role for vitamin D in the regulation of glucose metabolism in a setting of obese patients previously unknown to harbour glucose metabolism abnormalities.

Abdominal visceral tissue (VAT) and subcutaneous adipose tissue (SAT), comprised of superficial-SAT (sSAT) and deep-SAT (dSAT), are metabolically distinct. The antidiabetic agents thiazolidinediones (TZDs), in addition to their insulin-sensitizing effects, redistribute SAT suggesting that TZD action involves adipose tissue depot-specific regulation. We investigated the expression of proteins key to adipocyte metabolism on differentiated first passage (P1) preadipocytes treated with rosiglitazone, to establish a role for the diverse depots of abdominal adipose tissue in the insulin-sensitizing effects of TZDs. Adipocytes and preadipocytes were isolated from sSAT, dSAT, and VAT samples obtained from eight normal subjects. Preadipocytes (P1) left untreated (U) or treated with a classic differentiation cocktail (DI) including rosiglitazone (DIR) for 9 days were evaluated for strata-specific differences in differentiation including peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipoprotein lipase (LPL) expression, insulin sensitivity via adiponectin and glucose transport-4 (GLUT4), glucocorticoid metabolism with 11β-hydroxysteroid dehydrogenase type-1 (11βHSD1), and alterations in the adipokine leptin. While depot-specific differences were absent with the classic differentiation cocktail, with rosiglitazone sSAT had the most potent response followed by dSAT, whereas VAT was resistant to differentiation. With rosiglitazone, universal strata effects were observed for PPAR-γ, LPL, and leptin, with VAT in all cases expressing significantly lower basal expression levels. Clear dSAT-specific changes were observed with decreased intracellular GLUT4. Specific sSAT alterations included decreased 11βHSD1 whereas secreted adiponectin was potently upregulated in sSAT with respect to dSAT and VAT. Overall, the subcompartments of SAT, sSAT, and dSAT, appear to participate in the metabolic changes that arise with rosiglitazone administration.

Objective: To compare the predictive role of abdominal fat distribution by computed tomography (CT) with that of total abdominal fat by sagittal abdominal diameter (SAD) on cardiovascular risk in severe obesity.