Non-obese Age Research Articles

Nonalcoholic Fatty Liver Disease and Associated Risk Factors in Obese Nigerians: A Cross-Sectional Study.

Nonalcoholic fatty liver disease (NAFLD) is now adjudged the most common liver disease in the world, contributing to the rising incidence of hepatocellular carcinoma worldwide. However, the true prevalence of nonalcoholic fatty liver disease among obese individuals and its contribution to the burden of liver disease in Nigeria is unknown. To determine the prevalence of nonalcoholic fatty liver disease and associated risk factors in obese subjects. This was a cross-sectional analytical study of 280 obese subjects and 280 nonobese age and sex-matched controls seen at our health facility. Data collection was done using an interviewer-administered questionnaire and anthropometric parameters were obtained. Fasting blood samples were collected for blood glucose, lipid profile, and liver biochemistry. Abdominal ultrasound was used to screen for NAFLD. The results were subjected to relevant statistical analysis using SPSS version 20. A higher prevalence of NAFLD was found in obese subjects, compared with nonobese controls (36.4% versus 0.4% P < 0.001). The degree of obesity, transaminases, total cholesterol, diastolic hypertension, fasting blood glucose, and waist circumference was significantly associated with a higher prevalence of NAFLD. However, using multivariate logistic regression analysis, diabetes mellitus and hypertension were significant associations for NAFLD. Individuals with NAFLD had a significantly higher prevalence of metabolic syndrome 65.9%, compared with 34.1% in obese individuals without NAFLD (P < 0.001). The prevalence of NAFLD in obese subjects was significant. NAFLD in obese subjects was associated with degree of obesity, hyperlipidemia, hypertension, and diabetes mellitus.

Assessment of urinary podocalyxin as a marker of glomerular injury in obesity-related kidney disease in children and adolescents with obesity compared to urinary albumin creatinine ratio.

Obesity increases the risk of chronic kidney disease in children. Our aim was to assess urinary podocalyxin (PCX) in children and adolescents with obesity as a potential marker of obesity-related kidney disease (ORKD). The current case-control study included 128 children with obesity compared to 60 non-obese age and sex matched controls. Study population were subjected to full history taking as well as thorough physical examination. Urine samples for albumin creatinine ratio (uACR) and PCX were collected from the study population as well as blood samples for assessment of serum creatinine and fasting lipid profile. A statistically significant difference was found between cases and controls regarding urinary PCX (P < .001) and uACR (P=.021). A statistically significant positive correlation was found between uACR and weight SD score (SDS), body mass index SDS, waist circumference, estimated glomerular filtration rate, triglycerides (TG) as well as urinary PCX, whilst urinary PCX correlated significantly with obesity duration and uACR. Cases with microalbuminuria had a statistically significant higher waist circumference, waist-hip ratio, fat percentage, TG and urinary PCX compared to those with normal uACR (P=.042, .034, .05, .018 and .036 respectively). Urinary PCX showed 83.3% sensitivity and 74% specificity in detection of albuminuria. Urinary PCX was increased significantly in children with obesity making it a potential sensitive marker of ORKD in children.

SAT-047 Adoption of an Age Adjusted Testosterone Reference Range Reduces Referrals to Endocrine Clinic and New Prescriptions of Testosterone

Testosterone levels decline with age. However, until recently well defined harmonised age and/or obesity (BMI <30kg/m2) adjusted reference ranges did not exist.1 There is also a lack of international consensus on whether an age adjusted reference range (RR) should be used to define the syndrome of hypogonadism in men. Our local referral guideline suggests referral to endocrinology is appropriate if morning testosterone is <9.4nmol/L similar to the Endocrine Society Clinical Practice Guideline.2 In mid 2018 our laboratory adopted the published all men age adjusted RR1. We sought to; i) investigate clinic referrals before and after adoption of the all men age adjusted RR and, ii) to model the impact on referrals and prescription of testosterone replacement therapy (TRT) had we adopted either the lower limit of either all men or non-obese age adjusted RR as our referral criteria. Despite similar numbers of testosterone levels being measured in the laboratory, referrals to endocrine clinic for investigation of male hypogonadism fell by 52% (n=101 vs 48) in the one year following the introduction of the new age adjusted RR, with a corresponding reduction in prescriptions for testosterone. Mean testosterone concentration (6.7±2.5 vs 6.4±3.9nmol/L [mean±SD], NS), and age (51±13.9 vs 50±17.9 years, NS) of individuals referred were similar before and after the change of RR. Of the 101 patients referred for investigation of hypogonadism prior to the new RR mean testosterone concentrations were 8.5±4.5, 7.3±4.1, 6.8±3.6, 6.7±2.1 & 6.6±1.6nmol/L, with 39, 71, 39, 40 & 17% of the 87 patients seen in clinic being prescribed TRT in age groups 19-39 (n=28), 40-49 (n=7), 50-59 (n=33), 60-69 (n=20) &70-79 (n=6) respectively, excluding those with a history of anabolic steroid use or Klinefelter’s syndrome. Mean BMI was 30.9±4.4kg/m2, which was similar between age groups. Had the lower limit of normal of the all men testosterone RR been employed as our referral criteria in the preceding year, 23.8% (24/101) of referrals would not have met referral criteria, and 26.2% (n=11/42) of those receiving a prescription would potentially not have received a trial of TRT. In contrast, had the non-obese age adjusted RR had been adopted for all men 13.9% (14/101) of referrals would not have met referral criteria and, of those prescribed testosterone, 2.4% (n= 1/42) would not have received a trial of TRT. In conclusion, adoption of the all men age adjusted RR for testosterone has been associated with a significant fall in referrals for investigation of male hypogonadism. However, modelling of historical clinic data would suggest that some non-obese individuals miss out on a therapeutic trial of TRT, especially if the all men, rather than non-obese, age adjusted RR is adopted. Reference: (1) Travison et al, J Clin Endocrinol Metab, 2017,102(4):1161-1173, (2) Bhasin S et al,. J Clin Endocrinol Metab. March 2018;103(5):1715-1744.

Bone Health in Relation to Vitamin-D Status and Serum Adipokines in Obese Egyptian Children

Childhood obesity has been linked to an increase in fracture risk, so the impact of obesity on bone metabolism is becoming a focus of attention to identify factors that may affect bone health in obese children. Therefore, this study aimed to examine the association between serum 25-Hydroxy vitamin D [25(OH) D], adipokines and bone status in obese children. This case control study was executed in the Child Health Clinic in Medical and Scientific Centre of Excellence, National Research Centre (NRC), 100 obese and 80 non-obese age- and sex-matched children were enrolled in our study with mean age of (10.12±2.34 &amp; 9.62±1.67 years) respectively. Anthropometric measurements, femoral neck bone mineral density (BMD) and its Z-score, bone mineral content (BMC) were measured using dual-energy X-ray absorptiometry (DXA) in relation to body weight (kg), we also determined serum 25(OH) D, adiponectin, leptin and lipid profile. HOMA-IR was calculated to assess insulin resistance. It was found that BMC and BMD Z-score adjusted for weight were significantly lower in obese children as compared to controls (all p&lt;0.05). Obese children had lower levels of 25(OH) D and adiponectin (P&lt;0.01), while higher levels of leptin, total cholesterol (TC) and triglycerides (TG) compared to controls (P&lt;0.01). Both BMC and BMD Z-score showed positive association with 25(OH) D and adiponectin (P&lt;0.01) and negative association with HOMA-IR, TG and TC (P&lt;0.05). Linear regression analysis showed that 25(OH) D was the most effective factor predicting BMD Z-score and BMC in obese children. It is concluded that, obesity is negatively related to bone health in childhood. Those obese children are at increased risk for vitamin D insufficiency, which shows an obvious relationship to lower bone mass, raising the question of supplementation to prevent the deleterious effect of its deficiency on bones and reducing future risk of fracture and osteoporosis.

Habitual Physical Activity is Associated with Relative Apelin Gene Expression in Adipose Tissues Among Non-Diabetic Adults

The objective of the present study was to investigate the association between the apelin gene expression and habitual physical activity among morbid obese and non-obese subjects. Visceral and subcutaneous adipose tissues were obtained from 32 morbidly obese and 32 non-obese age- and sex-matched subjects, who underwent open abdominal surgery. Physical activity was collected using a valid and reliable International Physical Activity Questionnaire (IPAQ)-long form, and the metabolic equivalent of task (MET) was calculated. The mRNA expressions of apelin gene in visceral and subcutaneous adipose tissues were analyzed by Real-Time PCR. The mean age was 39.6 years for both groups and body mass index for morbidly obese and non-obese subjects were 45.3 and 25.7 kg/m2, respectively. Apelin gene expression was more increased in morbid obese than non-obese subjects in subcutaneous (2.82 vs. 0.70,P < 0.05) adipose tissues. After controlling for potential cofounders, apelin expression in subcutaneous adipose tissue was associated with total MET in both non-obese (β = 0.589, p value = 0.001) and morbid obese participants (β = 0.395, p value = 0.038). Among non-obese participants, apelin mRNA levels in visceral fat depots were associated with the total physical activity (β = 0.487, p value = 0.010). Moreover, occupational physical activity was associated with apelin gene expression in the subcutaneous adipose tissue of non-obese and morbid obese participants. Total MET was associated with apelin gene expression in visceral and subcutaneous adipose tissue in non-obese participants and was associated with only mRNA levels in subcutaneous fat depots in morbid obese participants.

Carotid intima-media thickness and cardiovascular risk factors in childhood and adolescent obesity

Background: Childhood obesity is a significant health problem that has reached epidemic proportions around the world and it is a risk factor for atherosclerosis. The study aimed to investigate carotid intima-media thickness (CIMT) in obese children and evaluate the relationship of CIMT to various cardiovascular risk factors.Methods: This was achieved through including 40 obese children aged 5-16 years who were referred to Alexandria University Children's Hospital (AUCH) and 20 non-obese age and sex-matched children as the control group. All obese children in this study were subjected to thorough history taking, thorough clinical examination stressing on anthropometric measurement, blood pressure measurement and laboratory investigations including lipid profile, liver function tests, fasting glucose and fasting insulin and ultrasonographic study for the liver and carotid intima-media thickness measurement.Results: compared to the control, the obese children demonstrated a significantly thicker carotid intima-media (p&lt;0.001). Univariate correlation analysis revealed that CIMT was significantly correlated with the body mass index (BMI), waist circumference measurement, diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDLC), fasting insulin, homeostasis model assessment- insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI) and fatty liver. In multiple linear regression analysis, CIMT correlated significantly with DBP in the obese group.Conclusions: Atherosclerosis begins in obese children and adolescents and CIMT measurement is a noninvasive, feasible, reliable and inexpensive method to detect subclinical atherosclerosis.

Obesity-induced changes in baseline immune responses to pre-clinical breast cancer

Abstract Obesity is known to increase morbidity and mortality in breast cancer patients; however, the immunological mechanisms behind these changes remain unclear. The long-term goal of our study is to investigate the broad impact of obesity on anti-tumor immunity, with a particular focus on better understanding immune alterations that may influence the use of immunotherapeutics in breast cancer patients. We began by utilizing the leptin-deficient ob/ob mouse model of obesity and non-obese age matched C57BL/6 controls, in combination with the syngeneic E0771 mammary carcinoma cell line. Tumor outgrowth was quantified by means of caliper measurements, endpoint tumor weight, and bioluminescent imaging (BLI) via luciferase-expressing E0771 (E0771-fLUC) cells; immune cell populations were evaluated via multi-parameter flow cytometry. Primary and metastatic tumor growth were not significantly different between lean and ob/ob mice. In primary tumors, we found that obesity caused significant decreases in the frequencies of tumor-infiltrating granulocytic myeloid derived suppressor cells (G-MDSCs) and CD19+ B cells, and trending decreases in the frequencies of T (CD3+, CD4+, and CD8+) cells. In spleens, we found that both obesity and breast cancer induced a significant decrease in the frequency of dendritic and natural killer (NK) cell populations. Additionally, obesity induced a significant increase in the frequency of splenic monocytic myeloid-derived suppressor cells (M-MDSCs). Our findings suggest several cellular candidates for future mechanistic investigations into obesity-induced dysfunctions in breast cancer immunity.

Associations between serum apelin-12 levels and obesity-related markers in Chinese children.

ObjectiveTo investigate possible correlations between apelin-12 levels and obesity in children in China and associations between apelin-12 and obesity-related markers, including lipids, insulin sensitivity and insulin resistance index (HOMA-IR).MethodsForty-eight obese and forty non-obese age- and gender-matched Chinese children were enrolled between June 2008 and June 2009. Mean age was 10.42±2.03 and 10.86±2.23 years in obesity and control groups, respectively. Main outcome measures were apelin-12, BMI, lipids, glucose and insulin. HOMA-IR was calculated for all subjects.ResultsAll obesity group subjects had significantly higher total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), insulin levels and HOMA-IR (all P<0.05). In separate analyses, obese girls had significantly higher LDL-C, insulin and HOMA-IR than controls, and obese boys had significantly higher TC, TG, insulin and HOMA-IR than controls (all P<0.05). Apelin-12 levels were significantly higher in obese girls compared to controls (P = 0.024), and correlated positively with TG in all obese subjects. Among obese girls, apelin-12 levels correlated positively with TG, insulin and HOMA-IR after adjusting for age and BMI. In all boys (obese and controls) apelin-12 was positively associated with fasting plasma glucose (FPG). No significant correlations were found in either group between apelin-12 levels and other characteristics after adjusting for age, sex, and BMI.ConclusionsApelin-12 levels are significantly higher in obese vs. non-obese girls in China and correlate significantly with obesity-related markers insulin, HOMA-IR, and TG. Increased apelin-12 levels may be involved in the pathological mechanism of childhood obesity.

Body Weight Loss by Very-Low-Calorie Diet Program Improves Small Artery Reactive Hyperemia in Severely Obese Patients

Endothelial dysfunction is a major underlying mechanism for the elevated cardiovascular risk associated with increased body weight. We aimed to assess the impact of weight loss induced by an intensive very-low-calorie diet (VLCD) on arterial wall function in severely obese patients (SOP). Thirty-four SOP were admitted to the metabolic ward of the hospital for a 3-week period. A VLCD characterized by a liquid diet providing 800 kcal/day was administered. The small artery reactivity to postischemic hyperemia index (saRHI), a surrogate marker of endothelial function, was assessed before and 1 week after hospital discharge. Anthropometry and biochemical parameters were also measured. Obese and non-obese age- and gender-matched groups were recruited for baseline comparisons. SOP had significantly lower saRHI compared with obese and non-obese individuals. SaRHI significantly increased after the intervention in SOP (1.595 ± 0.236 vs. 1.737 ± 0.417, p = 0.015). A significant improvement in glucose (p = 0.026), systolic blood pressure (p = 0.049), LDLc (p < 0.001), and inflammatory parameters was observed. Body weight loss was associated with a higher saRHI (r = -0.385, p = 0.033), and it was the main determinant of saRHI variation independently of confounders (β -0.049, IC 95 % -0.091-0.008, p = 0.021). Weight loss induced by a VLCD in SOP improved small artery reactivity, and it was associated with the amelioration of metabolic and inflammation markers. Endothelial dysfunction may be softened by body weight loss interventions and useful in the management of cardiovascular risk factors in SOP.

Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians

Glucocorticoids and its receptor are known to be involved in the dysregulation of hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and lipid levels in Northern Indians obese. A total of 435 obese and non-obese age matched subjects were included in the case-control study. Lipid and hormonal levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene polymorphism was done using PCR-RFLP. The frequencies of GR Bcl1, C>G genotypes and alleles did not differ significantly (P>0.05) between obese and non-obese. The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin and glucose levels than non-carriers in obese subjects while diastolic blood pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not associate with obesity. However, the GG genotype may modulate blood pressure, blood glucose and hormonal levels in northern Indians.

In VitroHyperresponsiveness to Tumor Necrosis Factor-α Contributes to Adipokine Dysregulation in Omental Adipocytes of Obese Subjects

Context: In obesity, adipocyte hypertrophy and macrophage infiltration lead to overproduction of proinflammatory adipokines, which play a crucial role in the metabolic syndrome. The molecular mechanisms underlying this overproduction are still unsettled. The role of TNF-alpha also remains controversial in human obesity. Objective: We revisited the contribution of TNF-alpha to adipokine dysregulation in central obesity. We more particularly assessed the involvement of TNF-alpha vs. other stromal-vascular cell (SVC)-secreted factors and searched for potential differential responses to TNF-alpha between adipocytes of lean and obese individuals. Design and participants: Primary cultures of omental adipocytes from obese and non-obese age- and sex-matched subjects were used. For some experiments, we generated media previously conditioned by SVC, which mimic adipocyte microenvironment. Results: Adipocytes of obese subjects mainly overexpressed adipokines, in comparison to those of lean ones, when cultured SVC-conditioned media. This was abrogated by immunoneutralization of TNF-alpha, indicating that among the numerous factors secreted by SVC, TNF-alpha is a crucial contributor to adipokine dysregulation. Accordingly, adipocytes of obese subjects overproduced adipokines in response to direct exposure of TNF-alpha. This hyper-responsiveness was mediated by TNF-alpha-receptor-1 and hyper-activation of the NF-kappaB pathway. Correspondingly, NF-kappaB activity was increased in adipocytes of obese subjects and correlated with adipocyte size, adipokine expression and in vivo insulin resistance. Eventually, adipokine overexpression in adipocytes of obese subjects was prevented by NF-kappaB inhibitors. Conclusions: In obesity, TNF-alpha that is, over other SVC-secreted factors, a crucial determinant of adipokine dysregulation acts on enlarged adipocytes, which are hyper-responsive to this triggering signal. This ultimately exacerbates adipokine production, inflammation and the metabolic syndrome.

In VitroHyperresponsiveness to Tumor Necrosis Factor-α Contributes to Adipokine Dysregulation in Omental Adipocytes of Obese Subjects

In obesity, adipocyte hypertrophy and macrophage infiltration lead to overproduction of proinflammatory adipokines, which play a crucial role in the metabolic syndrome. The molecular mechanisms underlying this overproduction are still unsettled. The role of TNF-alpha also remains controversial in human obesity. We revisited the contribution of TNF-alpha to adipokine dysregulation in central obesity. We more particularly assessed the involvement of TNF-alpha vs. other stromal-vascular cell (SVC)-secreted factors and searched for potential differential responses to TNF-alpha between adipocytes of lean and obese individuals. Primary cultures of omental adipocytes from obese and nonobese age- and sex-matched subjects were used. For some experiments, we generated media previously conditioned by SVCs, which mimic adipocyte microenvironment. Adipocytes of obese subjects mainly overexpressed adipokines, in comparison with those of lean ones, when cultured in SVC-conditioned media. This was abrogated by immunoneutralization of TNF-alpha, indicating that among the numerous factors secreted by SVCs, TNF-alpha is a crucial contributor to adipokine dysregulation. Accordingly, adipocytes of obese subjects overproduced adipokines in response to direct exposure of TNF-alpha. This hyperresponsiveness was mediated by TNF-alpha receptor 1 and hyperactivation of the nuclear factor-kappaB (NF-kappaB) pathway. Correspondingly, NF-kappaB activity was increased in adipocytes of obese subjects and correlated with adipocyte size, adipokine expression, and in vivo insulin resistance. Eventually adipokine overexpression in adipocytes of obese subjects was prevented by NF-kappaB inhibitors. In obesity, TNF-alpha that is [corrected] over other SVC-secreted factors, a crucial determinant of adipokine dysregulation acts on enlarged adipocytes, which are hyperresponsive to this triggering signal [corrected]

β-Cell Function in Morbidly Obese Subjects During Free Living

Insulin hypersecretion and insulin resistance are physiologically linked features of obesity. We tested whether extreme hypersecretion impairs beta-cell function under free-living conditions and whether major weight loss modifies insulin hypersecretion, insulin sensitivity, and beta-cell function. Plasma glucose, C-peptide, and free fatty acid concentrations were measured at hourly intervals during 24 h of normal life (including calorie-standardized meals) in 20 morbidly obese nondiabetic patients (BMI 48.4 +/- 1.7 kg/m2) and 7 nonobese age- and sex-matched control subjects; 8 of the obese patients were restudied 6 months and 2 years following biliopancreatic diversion. Insulin secretion was reconstructed from C-peptide levels by deconvolution and related to concurrent glucose levels through a mathematical model incorporating key features of beta-cell function: rate sensitivity, beta-cell glucose sensitivity, and potentiation. Insulin sensitivity (by the euglycemic insulin clamp technique) was reduced by 50% in obese subjects (23.1 +/- 2.5 of obese subjects vs. 52.9 +/- 4.9 micromol.min(-1) . kg(FFM)(-1) of control subjects, means +/- SE, P = 0.0004) as was mean 24-h insulin clearance (median 809 [interquartile range 451] vs. 1,553 [520] ml.min(-1) . m(-2), P < 0.001) due to a 50% reduction in hepatic insulin extraction (P < 0.01). Over 24 h, insulin secretion was doubled in obese subjects (468 nmol [202] in obese subjects vs. 235 [85] of control subjects, P=0.0002). Despite the hypersecretion, beta-cell glucose sensitivity, rate sensitivity, and potentiation were similar in obese and control subjects. Six months postoperatively (weight loss = 33 +/- 3 kg), both insulin hypersecretion (282 nmol [213]) and insulin sensitivity (51.6 +/- 3.7 micromol.min(-1).kg(FFM)(-1)) were normalized. At 2 years (weight loss = 50 +/- 8 kg), insulin sensitivity was supernormal (68.7 +/- 3.3 micromol.min(-1).kg(FFM)(-1)) and insulin secretion was lower than normal (167 nmol [37]) (both P < 0.05 vs. control subjects). In conclusion, severe uncomplicated obesity is characterized by gross insulin hypersecretion and insulin resistance, but the dynamic aspects of beta-cell function are intact. Malabsorptive bariatric surgery corrects both the insulin hypersecretion and the insulin resistance at a time when BMI is still high. With continued weight loss over a 2-year period, moderately obese subjects become supersensitive to insulin and, correspondingly, insulin hyposecretors.

The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults.

Several previous reports of small cohorts have found significantly higher serum 1,25-dihydroxy vitamin D (1,25-vit D) in obese compared with nonobese whites. Based on these reports and on recent in vitro studies of adipocytes which suggest that administration of 1,25-vit D can stimulate lipogenesis and inhibit lipolysis, some investigators have proposed that high 1,25-vit D may play a role in promoting or maintaining adipocyte triglyceride stores in obese adults. To test the hypothesis that obesity is commonly associated with increased 1,25-vit D, we examined the relationships between calciotropic hormones and body adiposity in a large cohort of healthy adults. Serum intact PTH, 25-hydroxy vitamin D, and 1,25-vit D were measured in the postabsorptive state in 302 healthy adults who were Caucasian (n = 190; 71% female), African-American (n = 84; 89% female), and of other race/ethnicity (n = 28; 61% female). Results from the 154 obese subjects [body mass index (BMI) 37.3 +/- 5.8 kg/m(2); range, 30.1-58.2 kg/m(2)] were compared with those from 148 nonobese (BMI 25.6 +/- 2.9 kg/m(2); range, 18.0-29.9 kg/m(2)) age-, race-, and sex-matched participants. Body composition was measured by dual energy x-ray absorptiometry. Serum intact PTH was positively correlated with both BMI (r = 0.42; P < 0.0001) and body fat mass (r = 0.37; P < 0.0001). Serum 25-hydroxy vitamin D was negatively correlated with BMI (r = -0.4; P < 0.0001) and body fat mass (r = -0.41; P < 0.0001). Serum 1,25-vit D was also negatively correlated with BMI (r = -0.26; P < 0.0001) and body fat mass (r = -0.25; P = 0.0001). Serum 1,25-vit D was significantly lower in obese than nonobese subjects (105.7 +/- 41.1 vs. 124.8 +/- 36.7 pmol/liter; P < 0.0001) in both Caucasian and African-American adults. We conclude that, because 1,25-vit D concentrations fall with increasing adiposity, it appears unlikely that elevation in 1,25-vit D is an important hormonal mechanism causing or maintaining obesity in adults.

Variants of uncoupling protein-2 gene and obesity: interaction with peroxisome proliferator-activated receptorgamma2.

To analyse the association of the UCP2 gene, alone or in combination with the PPARgamma2 gene, with obesity. Cross-sectional, case-control study. From a working population of 4500 Italian Caucasian employees of the Italian telephone company participating in a firm-sponsored health screening programme, we selected all those with obesity [n = 122; body mass index (BMI) > or = 30 kg/m2]. For each case, three nonobese age- and sex-matched individuals were selected as controls from the same population (n = 374). Included in the study were also 76 severely obese (BMI > or = 40 kg/m2) patients consecutively admitted to the obesity clinic of the department. Diabetic individuals were excluded. The -866G/A UCP2 and the Pro12Ala PPARgamma2 polymorphisms were determined on genomic DNA of the studied individuals. Several metabolic and anthropometric measures were also obtained, like plasma glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol and BMI. BMI, plasma glucose, insulin, triglycerides, total and HDL cholesterol were not significantly different in carriers and noncarriers of the -866G/A variant. No significant association was observed between the -866G/A UCP2 gene polymorphism and moderate or severe obesity. This was also observed when the UCP2 polymorphism was analysed in combination with the PPARgamma2 polymorphisms. The -866G/A variants of the UCP2 gene are not associated with either obesity or other features of the metabolic syndrome in the studied groups of the Italian population. This negative finding is not modified after a combined analysis of the UCP2 polymorphism and the Pro12Ala polymorphism of PPARgamma2.

A model for assessing insulin secretion and its control under free-living conditions.

A model for assessing insulin secretion and its control under free-living conditions.

FAD-Linked Glycerophosphate Dehydrogenase Activity in Islets, Liver, and Splenocytes of NOD Mice

The activity of FAD-linked glycerophosphate dehydrogenase (m-GDH), as well as that of glutamate dehydrogenase and both glutamate-oxalacetate and glutamate-pyruvate transaminases, were measured in islet, liver, and splenocyte homogenates from 6- to 7-week-old female nonobese diabetic mice (NOD) and age- and sex-matched control mice. Despite incipient insulitis and euglycemia, the NOD mice displayed both high islet insulin content and elevated insulinemia. The activity of m-GDH, expressed relative to protein content, was not decreased in islets of NOD mice, despite the fact that such a specific activity is lower in splenic lymphocytes than islet cells. In liver homogenates, the activity of m-GDH was even higher in NOD than control mice. It is proposed, therefore, that in this model of insulin-dependent diabetes no primary decrease in islet m-GDH activity occurs, at variance with the situation recently documented in several animal models of non-insulin-dependent diabetes.

Obesity Does Not Modulate Insulin Secretion in Indian Patients with Non-insulin-dependent Diabetes in the Young

The insulin response to a 100-g oral glucose load was studied in 40 obese (percent desirable weight greater than or equal to 120%) and 40 nonobese (less than 120%) age- and sex-matched Indian patients with non-insulin-dependent diabetes in the young. There were no significant differences between the obese and nonobese patients with respect to their insulin and glucose responses. Thus, it appears that obesity does not exert a significant modulating effect on insulin secretion in patients with fasting hyperglycemia.