Higher Risk Of Insulin Resistance Research Articles

Serum 25-hydroxyvitamin D and insulin resistance in apparently healthy adolescents.

PurposeVitamin D deficiency is a common condition that is associated with diabetes and insulin resistance. However, the association between vitamin D and insulin resistance has not been fully studied, especially in the general adolescent population. Therefore, we assessed the association between serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance among apparently healthy Korean adolescents.MethodsA total of 260 (135 male and 125 female) adolescents in a rural high school were assessed for serum 25(OH)D, fasting plasma glucose, and insulin. All of the participants were aged 15 to 16 years old, and without known hypertension or diabetes. Serum 25(OH)D was analyzed both as a continuous and categorical variable in association with insulin resistance. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Increased insulin resistance was operationally defined as a HOMA-IR value higher than the sex-specific 75th percentile.ResultsIn male adolescents, every 10 ng/ml decrease in 25(OH)D level was associated with a 0.25 unit increase in HOMA-IR (p = 0.003) after adjusting for age and BMI. Compared to those in the highest quartile, male adolescents in the lowest 25(OH)D quartile were at significantly higher risk for insulin resistance: unadjusted odds ratio 4.06 (95% CI, 1.26 to 13.07); age and BMI adjusted odds ratio 3.59 (95% CI, 1.03 to 12.57). However, 25(OH)D level, either in continuous or categorical measure, was not significantly associated with insulin resistance among female adolescents.ConclusionsThis study suggests that serum 25(OH)D level may be inversely associated with insulin resistance in healthy male adolescents.

The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults.

ObjectiveObesity is associated with a high risk of insulin resistance (IR) and its metabolic complications. It is still debated that distributions of adipose tissue relate to an excess risk of IR and chronic inflammation in different race. This study was designed to examine the relation between insulin sensitivity, chronic inflammation and central fat distribution in non-diabetic volunteers in Taiwanese.MethodsThere were 328 volunteers without family history of diabetes mellitus and with normal oral glucose tolerance test enrolled. Total body fat and abdominal fat were measured. Abdominal fat was categorized into intraperitoneal (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin, tumor necrosing factor-α (TNF-α), resistin and high sensitive CRP (hs-CRP) were measured.ResultsIR was related to IP fat (r = 0.23, p < 0.001), but not RP fat, SC fat or total body fat. After correcting for age and sex, IP fat was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p < 0.001; total body fat: r = 0.61, p < 0.001). The hs-CRP and adiponectin were closely related both to IP (r = 0.29, p = 0.004; r = -0.20, p = 0.046, respectively) and total body fat (r = 0.29, p = 0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-α and resistin were not correlated to any fat compartment. After correcting for age and sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly explained by IP fat (40% and 49% respectively).ConclusionsIP fat is better predictors of IR and subclinical chronic inflammation in Taiwanese adults. A disproportionate accumulation of abdominal fat is associated with increased risk of cardiovascular diseases.

Small-Molecule Inhibitors of PKR Improve Glucose Homeostasis in Obese Diabetic Mice

Obesity and metabolic diseases appear as clusters, often featuring high risk for insulin resistance and type 2 diabetes, and constitute a major global health problem with limited treatment options. Previous studies have shown that double-stranded RNA–dependent kinase, PKR, plays an important role in the nutrient/pathogen-sensing interface, and acts as a key modulator of chronic metabolic inflammation, insulin sensitivity, and glucose homeostasis in obesity. Recently, pathological PKR activation was also demonstrated in obese humans, strengthening its prospects as a potential drug target. Here, we investigate the use of two structurally distinct small-molecule inhibitors of PKR in the treatment of insulin resistance and type 2 diabetes in cells and in a mouse model of severe obesity and insulin resistance. Inhibition of PKR reduced stress-induced Jun NH2-terminal kinase activation and insulin receptor substrate 1 serine phosphorylation in vitro and in vivo. In addition, treatment with both PKR inhibitors reduced adipose tissue inflammation, improved insulin sensitivity, and improved glucose intolerance in mice after the establishment of obesity and insulin resistance. Our findings suggest that pharmacologically targeting PKR may be an effective therapeutic strategy for the treatment of insulin resistance and type 2 diabetes.

Dietary patterns and breakfast consumption in relation to insulin resistance in children. The Healthy Growth Study.

Insulin resistance is a significant cross-point for the manifestation of several chronic diseases in children and adults. The aim of the present study was to investigate the possible relationship of certain dietary patterns and breakfast consumption habits with insulin resistance in children. A representative sample of 1912 schoolchildren (aged 9-13 years) participated in a cross-sectional epidemiological study, the Healthy Growth Study, which was initiated in May 2007 and completed in June 2009. It was conducted in seventy-seven primary schools in four large regions in Greece. Dietary intake, breakfast consumption, anthropometric and physical examination data, biochemical indices and socio-economic information collected from parents were assessed in all children. Principal components analysis was used to identify dietary patterns. A dietary pattern of increased consumption of margarine, sweets (candies, lollipops, jellies, traditional fruit in heavy syrup) and savoury snacks (chips, cheese puffs and not home-made popcorn) was associated with homeostasis model assessment of insulin resistance index (HOMA-IR; β = 0·08, P < 0·001) in multivariate models. Children in the third tertile of this dietary pattern had a 2·51 (95 % CI 1·30, 4·90) times higher risk of insulin resistance (HOMA-IR > 3·16) than those in the first tertile. Breakfast consumption had an inverse correlation with insulin resistance, but the correlation lost its significance after adjustments for waist circumference, birth weight, parental BMI and socio-economic status. Increased consumption of margarine, sweets and savoury snacks, which is a common dietary pattern in childhood, was positively associated with insulin resistance, while breakfast consumption had an inverse association with HOMA-IR, in schoolchildren (aged 9-13 years). Identification of dietary behaviours that might affect insulin resistance in children offers valuable advice in cardiometabolic risk prevention strategies.

Correlation between serum adiponectin and clinical characteristics, biochemical parameters in Indian women with polycystic ovary syndrome.

Background:Polycystic ovary syndrome (PCOS) is a common disorder. PCOS women are at a high risk for insulin resistance and metabolic syndrome (MS). Adiponectin is positively related to insulin sensitivity. It has a preventive role in atherogenesis and MS. The present work was conducted to study the correlation between serum adiponectin levels and clinical characteristics and biochemical parameters in PCOS patients.Materials and Methods:A prospective study in 49 newly diagnosed (as per Rotterdam criteria) Indian PCOS women was conducted. PCOS women were clinically examined and investigated for biochemical parameters.Results:The mean serum adiponectin was 12 ± 9.4 μg/mL (range 0.47-45). Hypoadiponectinemia (serum adiponectin <4 μg/mL) was present in 22% patients. Age and adiponectin correlated significantly and inversely (r = −0.42, P = 0.027). Overweight/obese patients had lower mean adiponectin levels than normal weight (11.62 ± 9.5 vs 13.58 ± 9.5, P = 0.56). It was significantly lower in patients with acanthosis nigricans (AN) as compared with those without AN (8.4 ± 5.9 vs 15 ± 11, P = 0.038). Hirsute patients showed lower mean adiponectin levels than nonhirsute (10 ± 7.3 vs 13 ± 10, P = 0.57). A positive, insignificant correlation was observed between serum adiponectin and cholesterol, low-density lipoprotein, follicle stimulating hormone (FSH), thyroid stimulating hormone, levels. A negative insignificant correlation existed between serum adiponectin and luteinizing hormone (LH), LH: FSH ratio, prolactin, dehydroepiandrosterone, testosterone, triglyceride, high-density lipoprotein, fasting blood glucose, fasting insulin, and Homeostasis Model Assessment.Conclusion:Hypoadiponectinemia is present in one-fifth of women with PCOS. Adiponectin levels decrease as age advances. Low levels of adiponectin possibly contributes to the development of dermal manifestation (AN) of insulin resistance.

Excessive refined carbohydrates and scarce micronutrients intakes increase inflammatory mediators and insulin resistance in prepubertal and pubertal obese children independently of obesity.

Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient (P < 0.01). Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity.

Hepatobiliary Quiz-7 (2013)

1.Regarding the molecular virology of hepatitis E virus (HEV) the following are TRUE:1.HEV genome consists of three open reading frames (ORF)2.ORF1 codes for structural proteins3.The 5′ untranslated region is important for viral encapsidation4.The 3′ untranslated region is important for initiation of viral replication5.Unlike other positive strand ribonucleic acid (RNA) viruses, replication of HEV does not require a negative sense RNA intermediary2.Regarding the immunology of HEV the following are TRUE:1.First sign of infection is the detection of IgM antibodies2.Shedding of virus in feces commonly persists after onset of clinical disease3.IgG antibodies persist for years after infection and may protect from future infection4.Liver damage is immune mediated rather than due to direct cytotoxic effect of HEV5.Antibody mediated liver injury is more important than cellular mechanisms3.Regarding chronic HEV infection the following are TRUE:1.Chronic HEV infection is exclusively seen with genotype 3 in immunocompromised individuals2.HEV RNA positivity in solid organ transplant recipients is about 30%3.HEV infection in immunocompromised patients is severe with higher bilirubin and aminotransferase levels4.Chronic HEV infection can progress to cirrhosis5.Risk factors for chronic HEV infection include use of tacrolimus, higher degree of immunosuppression and large heterogeneity of quasispecies of HEV4.Regarding immunosuppressive agents used after liver transplantation the following are TRUE EXCEPT:1.Tacrolimus is more likely to cause diabetes than cyclosporine2.Gingival hyperplasia and hypertrichosis are common with tacrolimus3.Main advantage of using mycophenolate is absence of haematological side effects4.Sirolimus is has additional anti-tumour effects making it useful in cases of transplantation for hepatocellular carcinoma5.Basiliximab and daclizumab are IL-2receptor blocking antibodies5.Regarding involvement of the liver in sarcoidosis the following are TRUE EXCEPT:1.Majority of patients of sarcoidosis will have liver involvement on investigation2.Symptomatic liver disease is common in sarcoidosis3.Pulmonary involvement is absent in about 25% of hepatic sarcoidosis4.Portal hypertension is a common finding in hepatic sarcoidosis5.Sarcoidosis is not a cause for cirrhosis of the liver6.Regarding non-alcoholic fatty liver disease (NAFLD) in Asia the following are TRUE:1.South Asians like Indians are at a higher risk of insulin resistance than their Western counterparts2.India has a low prevalence of NAFLD3.Prevalence of NAFLD is increasing in Asian countries4.PNPLA3 gene polymorphisms are not associated with NAFLD in Asians5.APO C3 gene polymorphisms are associated with NAFLD predominantly in Caucasians7.Regarding liver transplantation for cirrhosis due to non-alcoholic steatohepatitis (NASH) the following are TRUE EXCEPT:1.Recurrence of NAFLD is very common2.Overall survival after transplantation is poorer compared to other etiologies of cirrhosis3.Renal dysfunction after transplantation is less common compared to other etiologies of cirrhosis4.Cardiovascular events are a more common cause of death after transplantation in NASH patients5.Pre-transplant diagnosis of NASH related cirrhosis is an independent predictor of development of metabolic syndrome after transplantation8.Regarding nutritional management of patients with cirrhosis the following are TRUE:1.Resting energy expenditure is lower in patients with cirrhosis2.Late evening snack of complex carbohydrates may improve quality of life and survival3.Protein restriction is not advisable even in patients with hepatic encephalopathy4.Animal protein is preferred to vegetable protein5.Branched chain amino acids improve event free survival9.Regarding management of ascites in cirrhosis the following are TRUE:1.Mean arterial pressure is a predictor of survival in patients of cirrhosis with ascites2.Angiotensin converting enzyme inhibitors are good anti-hypertensive drugs in patients with ascites3.Standard medical therapy consisting of sodium restriction and diuretics is successful in controlling ascites in 90% of cases4.Midodrine is a treatment option for patients with refractory ascites5.Peritoneovenous shunts are a favoured treatment option for refractory ascites10.Regarding spontaneous bacterial peritonitis (SBP) the following are TRUE:1.Culture-negative neutrocytic ascites has better outcome than culture positive SBP2.Monomicrobial non-neutrocytic bacterascites frequently resolves spontaneously3.Albumin infusions decrease mortality in patients with SBP4.Primary prophylaxis for SBP is indicated if Child score is ≥9 and serum bilirubin is ≥3 mg/dl5.Short-term prophylaxis for SBP in patients with gastrointestinal bleeding reduces infection rate but does not affect mortality

Indices of Insulin Resistance and Dyslipidemia Are Correlated with Lymphocyte Proneness to Apoptosis in Obese or Overweight Low Birth Weight Children

Aims: Our aim was to study the relationship between markers of cell proneness to apoptosis and indices of insulin resistance and dyslipidemia in children born with low birth weight (LBW). Methods: The study comprised 177 prepubertal children stratified by birth weight and their nutritional status into LBW (n = 138) and normal birth weight (NBW; n = 39) groups. We analyzed DNA from peripheral blood lymphocytes, separated by pulsed-field gel electrophoresis (PFGE), as well as the serum levels of cholesterol, HDL-cholesterol, triglycerides, fasting insulin and glucose, caspase 3, and BCL2. Results: LBW children with a BMI SDS >1.55 demonstrated increased content of the large fragments of the lymphocyte DNA [300-500 kb (DNA_{300-500 kb})] in electrophoretic slides (a marker of decreased chromatin stability and susceptibility of cells to apoptosis) compared to the NBW group. In these children the level of DNA_{300-500 kb} exhibited a strong negative correlation with the serum level of antiapoptotic protein of BCL2 (r = -0.901). DNA_{300-500 kb} significantly correlated with calculated indices of insulin resistance: HOMA-IR and QUICKI as well as with the indices of lipid homeostasis (Castelli and AIP). Conclusions: Increased susceptibility of lymphocytes to apoptosis correlated with a higher risk of insulin resistance and lipid disturbance in overweight or obese LBW children. A comprehensive study of the proneness of cells to apoptosis should be implemented to further investigate the pathomechanism of the metabolic syndrome in these children.

Role of Vitamin D in the Development of Insulin Resistance and Type 2 Diabetes

Vitamin D deficiency is mainly a consequence of insufficient sunlight induced vitamin D production in the skin and has been associated with various chronic diseases including type 2 diabetes. Experimental data have shown that vitamin D is important for glucose induced insulin secretion, improves insulin resistance, and exerts anti-inflammatory actions. Epidemiological studies have largely documented that a poor vitamin D status is associated with higher risk of insulin resistance and type 2 diabetes. The majority of randomized controlled trials (RCTs) in healthy or prediabetic individuals have, however, failed to demonstrate relevant vitamin D effects on insulin resistance or diabetes incidence. In patients with type 2 diabetes, a few RCTs reported some moderate effects of vitamin D on glycemic control and insulin resistance. While these findings warrant further in-depth studies, the current evidence is insufficient to recommend vitamin D supplementation for the prevention or treatment of type 2 diabetes.

Gender Difference in Association Between Appendicular Skeletal Muscle Mass and Cardiometabolic Abnormalities in Normal-Weight and Obese Adults

The objective of this study was to investigate whether the relationships of appendicular muscle mass (ASM) with insulin resistance (IR) and metabolic syndrome (MS) vary by gender or obesity. Data of 10 146 normal-weight and obese men and women aged 19 to 93 years from the Korea National Health and Nutrition Examination Survey in 2009 and 2010 were analyzed. In normal-weight men and women, unadjusted odds ratio (OR) of being MS and IR significantly increased with lower ASM/wt. After adjusting for lifestyle factors, these ORs were still significant in normal-weight men but not in women. After controlling for other covariates, lower ASM/wt was related to higher risk for IR but not to MS in obese men. In obese women, relationship of lower ASM/wt with higher risk for MS disappeared after adjusting for covariates. Association between skeletal muscle mass and cardiometabolic abnormalities is dependent on gender and obesity in Korean adults.

Cardiometabolic Aspects of the Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction, and finally cardiovascular disease and mortality. Further alterations in PCOS include an increased prevalence of sleep apnea, as well as various changes in the secretion and/or function of adipokines, adipose tissue-derived proinflammatory factors and gut hormones, all of them with direct or indirect influences on the complex signaling network that regulates metabolism, insulin sensitivity, and energy homeostasis. Reviews on the cardiometabolic aspects of PCOS are rare, and our knowledge from recent studies is expanding rapidly. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge, focusing on the alterations of cardiometabolic factors in women with PCOS. Further insight into this network of factors may facilitate finding therapeutic targets that should ameliorate not only ovarian dysfunction but also the various cardiometabolic alterations related to the syndrome.

UCP3 gene polymorphism and insulin resistance in obese female adolescents

Background A previous study on obese female adolescents inYogyakarta done in the year 2007 suggests that genetic factorsmight influence insulin resistance. One genetic factor that hasbeen associated \\lith insulin resistance in other populations isthe 􀁐55C;T polymorphism in the uncoupling protein 3 (UCP3)gene.Objective To investigate an association between the 􀁐55C;Tpolymorphism in the UCP3 gene and insulin resistance in obesefemale adolescents in Yogyakarta.Methods A total of79 obese female adolescents were enrolled inthis cross􀁐sectional study. Genotyping of the 􀁐 5 SC/T polymorphismin the UCP3 gene was performed by polymerase chain reaction􀁐restriction fragment length polymorphism (PCR􀁐RFLP).Results The TiT homozygous individuals had a higher risk ofinsulin resistance (OR 2.3; 95% CI 0.4 to 14.1), as well as higherfasting insulin concentration and homeostatic model assessmentfor insulin resistance (HOMA􀁐IR) compared to individuals v.ithother genotypes. The T allele carriers also had a higher risk ofinsulin resistance (OR 1.3; 95% CI 0.7 to 2.5), as well as higherfasting insulin concentration and HOMA􀁐 IR compared to Callele carriers. However, none of these results were statisticallysignificant (P &gt; 0.05).Conclusion The TiT genotype and T allele of the UCP3 gene􀁐55CiT polymorphism was not significantly associated increasedrisk of insulin resistance in obese female adolescents in Yogyakarta.[Paediatr lndanes. 2012;52:152-6].

Higher Metabolic Risk with National Institutes of Health Versus Rotterdam Diagnostic Criteria for Polycystic Ovarian Syndrome in Turkish Women

Polycystic ovary syndrome (PCOS) is a heterogeneous disease with well-established metabolic abnormalities in women of reproductive age. There are various diagnostic criteria to define and establish PCOS. However, data conflict regarding the optimal diagnostic criteria for PCOS and its metabolic consequences. We have evaluated the clinical, endocrine, and metabolic features between main PCOS phenotypes according to different diagnostic criteria. In this prospective, case-control study, 175 consecutive women with PCOS, 41 ovulatory women with idiopathic hirsutism, and 109 healthy, nonhirsute, ovulatory controls were enrolled. The following diagnostic criteria were assessed: Hirsutism; ovulatory function; ovarian sonography; gonadotropin, testosterone, dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone, fasting insulin, and lipid levels; oral glucose tolerance test; homeostasis model assessment for insulin resistance (HOMA-IR); body mass index (BMI); waist circumference; and the presence of metabolic syndrome. Of the 175 women meeting the Rotterdam criteria for PCOS, 121 (69%) had both androgen excess and ovulatory dysfunction, thus also meeting the National Institutes of Health (NIH) criteria. The other 54 (31%) had either androgen excess or ovulatory dysfunction. Women meeting the NIH criteria had the largest mean BMI, waist circumference, and HOMA-IR score; the highest mean testosterone, DHEA, triglyceride, and fasting insulin levels; the lowest mean progesterone level; and the greatest prevalence of insulin resistance (HOMA-IR score >3) among the groups. The NIH criteria identify women at high risk for insulin resistance and metabolic syndrome. The Rotterdam criteria include women who have less severe metabolic implications.

Fasting Plasma Glucose and Clustering of Cardiometabolic Risk Factors in Normoglycemic Outpatient Children and Adolescents

OBJECTIVETo evaluate whether fasting plasma glucose (FPG) within a normoglycemic range is associated with cardiometabolic risk factors (CMRF) among children and adolescents in an outpatient setting.RESEARCH DESIGN AND METHODSSubjects (780; age 6–16 years) with FPG <100 mg/dL were divided into tertiles of FPG.RESULTSBMI, waist circumference, homeostasis model assessment-insulin resistance, systolic blood pressure, and white blood cell (WBC) count (P < 0.0001) increased across tertiles of FPG. Subjects with high-normal FPG (89–99 mg/dL) showed a higher risk of insulin resistance, hypertension, and high WBC count compared with subjects with low-normal FPG, independent of BMI z score.CONCLUSIONSIn outpatient children and adolescents, higher FPG within the normal range is associated with several CMRF, independent of obesity. Thus the simple measurement of FPG may help identify subjects who warrant some monitoring in relation to cardiovascular risk.

Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: Risk reduction in a chronic inflammatory disease

To perform a systematic literature review of the potential association among molecular markers of inflammation, alterations in body composition, and insulin resistance (IR), a precursor to type 2 diabetes mellitus (DM), in rheumatoid arthritis (RA) patients. To determine the impact of tumor necrosis factor α (TNFα) as a pivotal proinflammatory cytokine in the pathophysiology of type 2 DM and RA, and the effect of antirheumatic drugs on glycemic control. We performed a search of PubMed to identify articles on IR and body habitus in patients with RA. Patients with RA had characteristics placing them at high risk for IR and type 2 DM. The incidence and prevalence of type 2 DM in RA was not clearly increased compared with the general population; however, studies suggested that patients with RA are likely to have IR and have increased risk of cardiovascular disease (CVD). The prevalence of type 2 DM and IR could be estimated from reports of risk factors for CVD in RA patients. The TNFα antagonists provided rapid and effective control of RA-related inflammation. Evidence indicated that extended use of TNFα antagonists in RA may provide the additional benefit of improving insulin sensitivity. These treatment-related changes may contribute to an overall reduction in the risk of type 2 DM and CVD in RA patients. Controlling inflammation may improve insulin sensitivity and subsequently reduce the risk of developing type 2 DM in RA patients. This may also reduce the risk of CVD in this high-risk group. Future studies are required to elucidate the relationships between inflammation, body composition, IR, TNFα antagonist use, and the risk of developing type 2 DM in RA patients.

Defining prediabetes in polycystic ovarian syndrome

Objective: The article will review the associations between Prediabetes (PD) and Polycystic Ovarian Syndrome (PCOS) and present factors that decrease the progression of PD into type 2 diabetes mellitus (T2DM).Metformin will also be examined for its role in ovulation induction, pregnancy and ameliorating the metabolic syndrome. Study Design: Medline search. Methods of study: Keyword search: Prediabetes (PD), Polycystic Ovarian Syndrome (PCOS), Metformin, Glucose Tolerance Test (GTT), Type 2 Diabetes Mellitus. Results: As the most common endocrinopathy during the reproductive years, PCOS has a genetic multifactorial inheritance and is associated with a high risk of insulin resistance. The use of metformin has shown mixed results in this patient population as a therapy to improve ovulation function and the metabolic syndrome and showed no definitive reduction in the rate of miscarriage. PCOS patients are significantly predisposed to PD and T2DM. Conclusion: Lifestyle changes such as weight loss and physical activity reduce the progression of PD into T2DM in PCOS patients. The new AACE and ADA guidelines establish simplified methods of screening and treating PD. The role of metformin remains undefined in the infertile PCOS patient.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Hypovitaminosis D and insulin resistance in peritoneal dialysis patients

An association between hypovitaminosis D and insulin resistance has been highlighted. Effects of vitamin D are not only mediated via the vitamin D receptors by active vitamin D metabolites, but 25(OH)D(3) also acts through VDR-independent pathways directly. It was reported that acute and chronic intravenous 1,25-dihydroxycholecalciferol therapy corrects insulin resistance in dialysis patients. There are no studies in patients on dialysis which evaluated relationship between 25(OH)D levels and insulin resistance. The aim of this study was to evaluate relationship between serum 25 (OH) D levels and insulin resistance in nondiabetic patients on peritoneal dialysis (PD). We studied 53 nondiabetic patients on PD and in 25 age-, gender- and body mass index-matched healthy controls. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels. Vitamin D deficiency was defined if 25(OH)D(3) levels are equal to or less to 15 ng/ml. Mean HOMA-IR index in patients on PD (3.1 ± 3.3) was significantly higher than those of controls (1.7 ± 1.9) (P < 0.05). The mean 25 (OH)D level in PD patients was (21.1 ± 19.0 ng/ml) lower than those of controls (27.5 ± 9.3 ng/ml) (P < 0.05). Twenty-five (47.2%) PD patients had vitamin D deficiency [mean 25(OH)D: 7.2 ± 3.2 ng/ml], and in 28 of them (52.8%) 25 (OH)D levels were more than 15 ng/ml (mean 33.5 ± 18.7 ng/ml). In PD patients with vitamin D deficiency, mean HOMA-IR index (4.2 ± 3.8) was significantly higher than that of PD patients whose 25 (OH)D levels were more than 15 ng/ml (2.2 ± 2.4) (P < 0.05). Twenty-one (84.0%) of PD patients with vitamin D deficiency, and 22 (78.6%) PD patients whose 25 (OH)D levels were more than 15 ng/mL have been receiving active vitamin D compounds for parathyroid hormone (PTH) control (P > 0.05). There was no significant difference between two PD groups according to mean duration of PD, age, gender, PTH, serum calcium, phosphorus, percentage of fat, and body mass index. There was a negative correlation between HOMA-IR index and 25 (OH)D levels in PD patients (r: -0,368, P < 0,05). In multiple regression analyses, the independent predictors of HOMA-IR index were 25(OH)D3 levels, duration of dialysis, and percentage of fat (measured by bioelectrical impedance) in PD patients. Our findings show a negative correlation of 25(OH)D levels with insulin resistance in PD patients. PD patients with hypovitaminosis D are at higher risk of insulin resistance even if they are on treatment with active vitamin D for PTH control. Further studies are required to explore the relation between vitamin D deficiency and insulin resistance in PD patients.

Reference curves and cut-off values for anthropometric indices of adiposity of affluent Asian Indian children aged 3–18 years

Background: Asian Indians as an ethnic group are at particularly high risk of insulin resistance and central obesity. It is now emerging convincingly that these disorders begin in childhood. No satisfactory reference curves and cut-off points for overall or central adiposity exist for Indian children.Aim: To present reference curves and age- and sex-specific cut-off points for the body mass index (BMI) and waist circumference (WC) of affluent Asian Indian children.Subjects and methods: Cole's LMS method was applied to longitudinal data on a cohort of 320 affluent, physically active children representing the five major geographical regions of India to derive smoothed BMI and WC centile curves. Age- and sex-specific cut-off points for overall and central adiposity were derived by identifying centiles analogous to adult Asian Indian cut-off values.Results: Adult BMI cut-offs for overweight/obesity corresponded to the 87th/96th and the 82nd/93rd centiles in boys and girls, respectively. Adult WC cut-offs for men and women corresponded to the 95th and 96th centiles in boys and girls, respectively. Age- and sex-specific BMI and WC cut-off points for Asian Indian children aged 3–18 years are described for the first time.Conclusions: These reference data could be used to identify affluent Asian Indian children with an elevated risk of developing obesity-related disorders and provide a baseline for future studies.

The Role of the Flushing Response in the Relationship Between Alcohol Consumption and Insulin Resistance

Facial flushing responses to drinking, because of intolerance to alcohol, are observed in some people, especially Asians. This study examined the role of flushing responses in the relationship between alcohol consumption and insulin resistance (IR). Participants in this cross-sectional analysis included 624 Korean men (80 nondrinkers, 306 nonflushing drinkers, and 238 flushing drinkers) who were free of cardiovascular disease and diabetes. Data on the flushing response to drinking and alcohol consumption were collected from medical records. IR was estimated using the Homeostasis Model Assessment (HOMA(IR) ). On the basis of comparisons with nondrinkers, the risk of IR according to the quantity of alcohol consumed per week was analyzed among nonflushers and flushers. After adjusting for age, exercise status, smoking status, BMI, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triglycerides using a logistic regression model, we found a low risk of IR among nonflushers who consumed ≤4 drinks (1 drink = 14 g of alcohol) per week (OR = 0.3). In contrast, a higher risk of IR was associated with nonflushers who consumed >20 drinks per week (OR = 3.5). On the other hand, only a higher risk of IR was associated with flushers who consumed >12 drinks per week (>12 to 20 drinks: OR = 4.7; >20 drinks: OR = 3.5). The amount of drinking associated with the development of IR in flushers was lower than in nonflushers. Additionally, no positive effect of moderate drinking on IR was observed in flushers. The findings support acetaldehyde-derived mechanisms in the development of alcohol-related IR.