Homeostasis Model Assessment Values Research Articles

Differences in the associations of anthropometric measures with insulin resistance and type 2 diabetes mellitus between Korean and US populations: Comparisons of representative nationwide sample data

Variation among ethnic groups in the association between obesity and insulin resistance (IR)/diabetes has been suggested, but studies reported inconsistent results. We evaluated ethnic differences in the association between obesity and insulin resistance (IR)/diabetes. We conducted a cross-sectional analysis using Korea (n=18,845) and the USA (n=4657) National Health and Nutrition Examination Survey(NHANES) 2007-2010. We performed statistical comparisons of AUC-ROC (area under the curve in a receiver operating characteristic curve) values for body mass index (BMI), waist circumference (WC) and homeostasis model assessment of insulin resistance (HOMA-IR) to predict IR or diabetes among different ethnic groups. AUC-ROC values for BMI and WC for predicting IR were highest in Whites (0.8324 and 0.8468) and lowest in Koreans (0.7422 and 0.7367). Whites showed the highest AUC-ROC values for BMI (0.6869) and WC (0.7421) for predicting diabetes, while the AUC-ROC for HOMA-IR was highest in Koreans (0.8861). Linear regression showed significant interactions between ethnicity and the main effects (all P<0.0001). Increases in BMI were associated with a larger increase in HOMA-IR in Whites (β=0.0719) and WC in Hispanics (β=0.0324), while BMI was associated with a larger increase in fasting glucose in Koreans (β=0.8279) and WC in Blacks (β=0.4037). In addition, the slope for fasting glucose with increasing HOMA-IR was steeper in Koreans (β=16.5952, P<0.001) than in other groups. The ability of BMI and WC to predict IR and diabetes was highest in Whites, while the ability of HOMA-IR to predict diabetes was highest in Koreans.

Phenotype, Body Composition, and Prediction Equations (Indian Fatty Liver Index) for Non-Alcoholic Fatty Liver Disease in Non-Diabetic Asian Indians: A Case-Control Study.

ObjectiveIn this study, we have attempted comparison of detailed body composition phenotype of Asian Indians with non-alcoholic fatty liver disease (NAFLD) vs. those without, in a case controlled manner. We also aim to analyse prediction equations for NAFLD for non-diabetic Asian Indians, and compare performance of these with published prediction equations researched from other populations.MethodsIn this case-control study, 162 cases and 173 age-and sex-matched controls were recruited. Clinical, anthropometric, metabolic, and body composition profiles, and liver ultrasound were done. Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR), and serum high sensitive C-reactive protein (hs-CRP) levels were evaluated. Multivariate logistic and linear regression analyses were used to arrive at prediction equations for fatty liver [Indian fatty liver index (IFLI)].ResultsAs compared to those without fatty liver, those with fatty liver exhibited the following; Excess dorsocervical fat (‘Buffalo hump’), skin tags, xanthelasma, ‘double chin’, arcus; excess total, abdominal and subcutaneous adiposity, and high blood pressure, blood glucose, measures of insulin resistance (fasting insulin and HOMA-IR values), lipids and hs-CRP levels. Two prediction equations were developed; Clinical [Indian Fatty Liver Index-Clinical; IFLI-C]: 1(double chin) +15.5 (systolic blood pressure) +13.8 (buffalo hump); and IFLI-Clinical and Biochemical (CB): serum triglycerides+12 (insulin)+1(systolic blood pressure) +18 (buffalo hump). On ROC Curve analysis, IFLI performed better than all published prediction equations, except one.ConclusionNon-diabetic Asian Indians with NAFLD researched by us were overweight/obese, had excess abdominal and subcutaneous fat, multiple other phenotypic markers, had higher insulin resistance, glycemia, dyslipidemia and subclinical inflammation than those without. Prediction score developed by us for NAFLD; IFLI-C and IFLI-CB, should be useful for clinicians and researchers.

Hyperleptinaemia, insulin resistance and survival in peritoneal dialysis patients.

The aim of this study was to clarify the relationship between insulin resistance (IR) and glucose and lipid metabolism in peritoneal dialysis (PD) patients. The study also investigated the prognostic factors for survival in long-term peritoneal dialysis patients. Participants were recruited from July 1 to August 1, 2011, based on selection criteria. Patients were divided into two groups, high (H) and low (L) group according to the median value of homeostasis model assessment of IR (HOMA-IR). Type 2 diabetes mellitus (DM) patients were chosen as positive controls. Clinical, plasma biochemical and metabolic parameters were observed and recorded at the outset and follow-up of this study. Mortality related factors were also detected, and statistical analyses were performed. A total of 157 cases with an average age of 55 ± 15 years were included. There were 26, 66 and 65 cases in the DM, H and L groups, respectively. Younger age, lower body mass index, high sensitive C-reactive protein (hsCRP) level, higher normalized protein catabolic rate (nPCR) were found in the L group compared with the other two groups. HOMA-IR positively correlated with age, leptin and triglyceride levels, and it negatively correlated with BMI. L group had better survival rate than H and DM groups. Dialysis duration, serum leptin level, nPCR and hsCRP were statistically associated with mortality. Insulin resistance may play an important role in the pathophysiology of glucose and lipid metabolism. Dialysis duration, leptin, nPCR and hsCRP may be risk factors for mortality in PD patients.

Predictors of metabolic syndrome persistence 1 year after laparoscopic Roux-en-Y gastric bypass

BackgroundLaparoscopic Roux-en-Y gastric bypass (LRYGB) is effective in reversing the metabolic syndrome (MS) in up to 90% of patients. ObjectivesThe aim of this study was to determine predictors of MS persistence 1 year after LRYGB. SettingUniversity Hospital, France. MethodsNinety-one patients with a mean age of 44.4 years and a mean body mass index (BMI) of 43.1 kg/m² meeting the criteria for MS were enrolled in this prospective study. Anthropometric, metabolic, and inflammatory biological parameters were assessed before and 1 year after LRYGB. Patients were divided into 2 groups according to the persistence (MS nonresponders) or resolution of MS (MS responders) 1 year after LRYGB and a comparison was performed at baseline and 1 year after surgery. ResultsSixty-nine patients (75.8%) underwent remission, while 22 (24.2%) showed persistence of MS 1 year after LRYGB. At baseline the MS nonresponders group presented significantly higher values of fasting plasma glucose (7.8 versus 5.3 mmol/L, P = .004), glycosylated hemoglobin (HbA1c, 7.3% versus 5.9%, P = .0004), triglycerides (TG, 2.37 versus 1.33 mmol/L, P = .006), and homeostasis model assessment of insulin resistance (HOMA-IR, 442.5 versus 256, P = .006). The rate of diabetes was significantly higher in this group (68.2% versus 36.8%, P = .0086), as well as the number of MS components per patient. One year after LRYGB, the MS nonresponders showed a significantly lower excess BMI lost (EBMIL) (56.1% versus 82.4%, P = .00008). On multivariate analysis, baseline levels of TG, glucose metabolism markers and EBMIL were associated with the persistence of MS. ConclusionBaseline levels of TG, plasma fasting glucose, and HbA1c, as well as history of type 2 diabetes and EBMIL, represent predictors of MS persistence 1 year after LRYGB.

The threshold value of homeostasis model assessment for insulin resistance in Qazvin Metabolic Diseases Study (QMDS): assessment of metabolic syndrome.

The homeostasis model assessment of insulin resistance (HOMA-IR) is a useful model for application at large epidemiologic studies. The aim of this study was to determine the HOMA cut off values to identify insulin resistance (IR) and metabolic syndrome (MS) in Qazvin, central Iran. Overall, 480 men and 502 women aged 20-72 yr attended in this cross sectional study from September 2010 to April 2011. The diagnostic criteria proposed by national cholesterol education program third adult treatment panel (ATPIII), International Diabetes Federation (IDF) and new Joint Interim Societies (JIS); were applied to define MS. Lower limit of the top quintile of HOMA values in normal subjects was considered as the threshold of IR. The receiver operating characteristic (ROC) curves of HOMA for MS diagnosis were depicted. The optimal cut point to determine MS was assessed by maximum Youden index and the shortest distance from the point (0, 1) on the ROC curve. The threshold of HOMA for IR was 2.48. Fifty one percent of the subjects were insulin resistant. The cut point for diagnosis of JIS, IDF, ATP III and Persian IDF defined MS was 2.92, 2.91, 2.49 and 3.21, respectively. Sensitivity and specificity of ATP III defined MS to diagnose IR was 33.95% and 84.78%, of IDF defined MS was 39.13%, 81.29% and of JIS defined MS was 43.77% and 78.11% and of Persian IDF defined MS was 27.32% and 88.76%, in that order. The high prevalence of IR in the present study warns about the future burden of type 2 diabetes. Only the ATP III criteria introduced more specific cut point for putative manifestations of IR.

Insulin resistance in severe acne vulgaris.

IntroductionAcne vulgaris is a pilosebaceous gland disease that usually affects people from puberty to young adulthood. It is seen especially on the face, neck, trunk and arms. Its severity differs from patient to patient and its pathogenesis is multifactorial. The main pathogenic factors of acne are high sebaceous gland secretion, follicular hyperproliferation, high androgen effects, propionibacterium acnes colonization and inflammation. Diet is always thought a probable reason for acne and many studies are done about acne and diet.AimTo determine the effect of insulin resistance in severe acne vulgaris.Material and methodsTwo hundred and forty-three acne vulgaris patients and 156 healthy controls were enrolled into the study. The blood levels of insulin and glucose were measured. Homeostasis Model Assessment (HOMA) Index was calculated. The values were compared with the control group.ResultsAll of the patients were in the severe acne group according to their scores on the global acne scoring scale. While fasting blood glucose levels were not different between the groups (p > 0.05, 82.91 ±9.76 vs. 80.26 ±8.33), the fasting insulin levels were significantly higher in the patient group than in the control group (p < 0.001, 14.01 ±11.94 vs. 9.12 ±3.53). Additionally, there was a highly significant difference between the patient and control groups in terms of HOMA values (p < 0.001, 2.87 ±2.56 vs. 1.63 ±0.65).ConclusionsThese results suggest that insulin resistance may have a role in the pathogenesis of acne.

Abstract 14866: Hyperglycemia is an Independent Predictor of Left Ventricular Hypertrophy

Background: Diabetes mellitus (DM) is a risk factor for cardiovascular morbidity and mortality. In the current study we examine the association of hyperglycemic with left ventricular hypertrophy (LVH) independent of major correlates of LVH, such as, age, body size, blood pressure (BP) and aortic stiffness. Methods: We conducted a population-based, cross-sectional survey in 8,080 South Indians over the age of 20 years. The study included anthropometric, socioeconomic, psychosocial, BP, blood lipids, insulin, HbA1C, glucose tolerance test and carotid-femoral pulse wave velocity (PWV) assessments. Insulin resistance (IR) was defined as the 25% of the population with the highest values for homeostasis model assessment of insulin resistance (HOMA-IR). LV mass and relative wall thickness (RWT) were determined using echocardiography. LVH was defined as LV mass index (LVMI) &gt;109 g/m 2 for men and &gt;89 g/m 2 for women. Results: After the exclusion of people with hypertension, 5,841 subjects (mean age 41 years, 59% women) constituted the study sample. The mean LVMI in subjects with normoglycemia (n=3585), pre-DM (impaired fasting and/or post prandial blood sugar; n=1315) and DM (n=888) was 78.5 ± 17.5, 80.7 ± 19.4 and 87.2 ± 20.3, while mean RWT was 0.46 ± 0.09, 0.48 ± 0.09 and 0.51 ± 0.1, respectively (p&lt;0.01). After adjustments for age, sex, BMI, BP, PWV, blood lipids, history of coronary artery disease, socioeconomic and smoking status, and physical activity, when compared to persons with normoglycemia, the odds ratio (95% CI) for LVH in pre-DM and DM men was 1.12 (0.89, 1.42) and 1.37 (1.04, 1.8), respectively; the odds ratio in pre-DM and DM women was 1.07 (0.89, 1.28) and 1.4 (1.08, 1.82), respectively. Among the persons with normoglycemia those with IR the odds ratio for LVH was 1.23 (0.85, 1.78) in men and 1.01 (0.79, 1.30) in women. In the multi-linear regression models HbA1c was independently correlated with LVMI. The correlation coefficients were higher in men (β= 0.07, p &lt;0.001) compared to women (β= 0.037, p = 0.032). Conclusion: Hyperglycemia is an independent predictor of LVH in South Asian population. These findings indicate potential adverse myocardial effects of DM independent of associated risk factors, such as obesity, BP and aortic stiffness.

The Association between Sleep Duration and Metabolic Variables in Obese Children with Obstructive Sleep Apnea

Objectives: Sleep loss is problematic in adults and children. Decline in sleep duration has paralleled an increase in the prevalence of obesity and diabetes. The aim of this study was to analyze the association between sleep duration, severity of obstructive sleep apnea (OSA), and metabolic variables in obese children. Methods: In this study, patients between the ages of 2 and 12 years who had overnight polysomnography (PSG) at a tertiary care medical center were included. Patients were identified from a xenobase search of medical records. All patients had lipid levels, blood glucose, and insulin evaluated within 3 months of PSG. The demographics, laboratory data, body mass index (BMI), and blood pressure were collected from the medical records. Results: A total of 31 patients were studied. Twenty-one (67.7%) were male, and the mean age of patients was 8.5 ± 1.9 years. The mean BMI z score was 2.7 ± 0.81. All patients were obese. Patients were categorized into groups with total sleep duration &gt;6 hours and &lt;6 hours. Sixteen patients slept &lt;6 hours and 15 patients slept &gt;6 hours. There was no statistical difference in the lipid variables and blood pressure in these patients. A nonsignificant trend of decreased sleep duration with an increase in severity of OSA was observed. Blood sugar was significantly increased in patients with sleep &lt;6 hours (100.2 ± 8.1 mg/dL) when compared with patients with sleep &gt;6 hours (95 ± 4.4 mg/dL; P = .05). The homeostasis model assessment (HOMA) values were significantly higher in children with sleep &lt;6 hours (1.81 ± 0.51) when compared with patients with sleep &gt;6 hours (1.33 ± 0.55; P = .04). Conclusions: Short sleep duration is associated with insulin resistance in obese children with OSA.

The Comparison of Glycated Hemoglobin and Homeostasis Model Assessment Values to 30, 60 and 90-Min Glucose Levels During OGTT in Subjects with Normal Glucose Tolerance

Abstract Background: The subjects with impaired glucose tolerance have an increased risk for future type 2 diabetes (T2DM); however, a significant number of individuals who develop T2DM have normal glucose tolerance (NGT) at baseline. The study aims to compare glycated hemoglobin (HbA1C) and homeostasis model assessment (HOMA-IR) levels to 30, 60 and 90-min glucose levels in subjects with NGT. Methods: A 75-g oral glucose tolerance test (OGTT) at 0, 30, 60, 90 and 120-min was performed in 1118 subjects without known T2DM. Blood samples were also drawn for fasting insulin and HbA1C levels. Results: Forty percent of the subjects with NGT had increased post-challenge values above the determined optimal glucose levels (10.2, 10.3 and 8.9 mmol/L at 30, 60 and 90-min, respectively). Compared to the subjects with NGT whose glucose levels were below the determined optimal values at 30, 60 and 90-min, we found significantly elevated HbA1C and HOMA-IR levels in the subjects with NGT whose glucose levels were above the determined optimal values (p&lt;0.001). Conclusions: We conclude that the subjects with NGT have different HbA1C and HOMA-IR levels considering glucose levels measured earlier than at 2-h during OGTT. Further well-designed prospective studies are needed to define the significance of 30-min, 60-min and 90-min glucose levels in the prediction of disease in subjects with T2DM.

High prevalence of metabolic syndrome and of insulin resistance in psoriatic arthritis is associated with the severity of underlying disease.

To investigate the prevalence of metabolic syndrome (MetS) and of insulin resistance (IR) in an ethnically homogeneous cohort of established psoriatic arthritis (PsA), and to identify clinical associations of MetS and IR in patients with PsA. A cohort of 283 patients with PsA all meeting ClASsification for Psoriatic ARthritis (CASPAR) criteria was included. All underwent detailed skin and rheumatologic assessments, along with cardiovascular risk factor evaluation. IR was defined as an elevated homeostasis model assessment (HOMA-IR) value of > 2.5. Severe PsA was defined as the presence of 1 or more of the PsA-related radiographic damage features (peripheral joint erosions, osteolysis, sacroiliitis), and PsA requiring tumor necrosis factor inhibitor therapy. The demographic and clinical characteristics of the cohort were mean age 54.6 ± 12 years, 52% female, mean PsA duration 19 ± 9 years. MetS was present in 44% of the studied patients (n = 283). On multiple regression analysis, a significant association of MetS was noted with more severe PsA (OR 4.47, p < 0.001), higher smoking pack-years (OR 1.03, p = 0.02), and worse EQ-5D scores (OR 1.28, p = 0.02). Data on IR were available for 263 patients, and among them, the mean HOMA-IR was 1.43 ± 1.09. Forty-one patients (16%) had IR. On multiple regression analysis, a significant association of IR was noted with more severe PsA (OR 3.49, p = 0.03), later psoriasis age of onset (OR 1.07, p = 0.001), and higher body mass index (OR 1.22, p < 0.001). Among patients with PsA, MetS and IR are highly prevalent, and are independently associated with the severity of underlying PsA.

Williams-Beuren Syndrome Is a Genetic Disorder Associated with Impaired Glucose Tolerance and Diabetes in Childhood and Adolescence: New Insights from a Longitudinal Study

Background: In adults with Williams-Beuren syndrome (WBS), a common endocrine abnormality is type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). However, few and sporadic data are available in children, adolescents, and young adults with WBS. Aim: To evaluate the frequency of IGT and T2DM in a cohort of children and young patients with WBS. Patients and Methods: We longitudinally evaluated 27 patients (9 males and 18 females, median age at study onset 13.6 years) with WBS. The median follow-up was 3.6 years. Variables of insulin resistance and β-cell function were evaluated in all subjects using an oral glucose tolerance test. The homeostasis model assessment (HOMA) of insulin resistance and the Matsuda index of insulin sensitivity were calculated. The study of the GCK and HNF1Α genes was performed in patients with glucose metabolism abnormalities. 45 age- and sex-matched healthy subjects and 51 age-, sex- and BMI-matched subjects were recruited as two control groups. Results: Considering nutritional status, 7 (25.9%) patients were obese, 9 (33.3%) overweight, and 11 (40.8%) normal-weight. One (3.1%) patient had acanthosis nigricans. IGT was diagnosed in 7 (25.9%) WBS patients and T2DM in 3 (11.1%). Considering all WBS patients, the median value of HOMA was 5.23 (range 2.93-14.89; insulin 24.73 ± 14.67 μU/ml; glucose 104.98 ± 16.06 mg/dl). Considering BMI values, HOMA was 11.00 (range 6.53-12.56), 5.64 (range 3.54-7.95), and 4.54 (range 3.21-5.43), and insulin was 34.53 ± 6.84, 22.76 ± 8.91, and 19.47 ± 6.01 μU/ml in obese, overweight, and normal-weight WBS patients, respectively. Comparing the results with the two control groups, WBS patients showed higher insulin values than healthy controls (p < 0.001), but similar values as the BMI-matched control group (p = n.s.). However, WBS patients showed significantly higher values of glycemia (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) and HOMA (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) than the two control groups. Finally, among WBS patients there was a higher number of subjects with IGT and T2DM than among healthy controls (p < 0.0001) and the BMI-matched control group (p = 0.0002). Conclusion: Our data strongly suggest that IGT and T2DM may be frequently discovered in children, adolescents, and young adults with WBS. WBS should be included among the genetic syndromes associated with T2DM. Further studies are necessary to evaluate the etiopathogenesis of this aspect.

Non-alcoholic fatty liver disease in patients with chronic viral hepatitis

Aim. To estimate the prevalence of non-acloholic fatty liver disease in patients with chronic hepatitis B, and the association of non-acloholic fatty liver disease with the biochemical, virological and metabolic faсtors. Methods. 53 patients with chronic hepatitis B observed in the regional hospital of infective diseases, Stavropol, at 2008-2012, were included. Patients were distributed to 2 groups according to the results of liver biopsies: group I - patients with hepatosteatosis (5%) and group II - no signs of steatosis (≤5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Results. Of 53 patients, 18 (34%) liver biopsies had signs of steatosis. Patients with steatosis (group I), compared with group II, were older (43±13 vs 34.5±10.9 years, р=0.015), had higher body mass index (30±5.3 vs 22.9±4.3 kg/m 2, р=0.015), higher level of triglycerides (1.6±0.8 vs 1.06±0.7 mmol/l, р=0.014), higher level of cholesterol (5.6±0.7 vs 4.97±0.9 mmol/l, р=0.012), and higher serum insulin (13±7.9 vs 8.2±3 mkME/l, р=0.002) and leptin levels (16.2±15.6 vs 6.5±5.2 ng/ml, р=0.001). The values of HOMA (Homeostasis Model Assessment) and QUICKI (quantitative insulin sensitivity check index) indices corresponded to insulin resistance (НОМА 2.9±1.8 and 1.9±0.8, р=0.007; QUICKI 0.33±0.02 and 0.35±0.03, р=0.014). There were no differences in histological activity scores by Knodell and fibrosis scores by METAVIR scale between the groups. No reliable differences in virological parameters (viral load and HBeAg status) were obtained. Conclusion. Non-alcoholic fatty liver disease is observed in one-third of patients with hepatitis B and is associated with host metabolic factors, which correspond to the parameters of metabolic syndrome.

Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men.

AIMSEssential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters.METHODSQ192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R).RESULTSGenotype frequencies were consistent with the Hardy–Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACHAUC values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes.CONCLUSIONSQ192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men.

Insulin resistance determined by Homeostasis Model Assessment (HOMA) and associations with metabolic syndrome among Chinese children and teenagers

ObjectiveThe aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk.Methods3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS.ResultsWith the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively.ConclusionsOur data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut-off points in this cohort were developed with variation regarding puberty. HOMA-IR may be useful for early evaluating insulin resistance in children and teenagers and could have a long-term benefit of preventive and diagnostic therapeutic intervention.

Serum leptin, adiponectin, and resistin among adult patients with acanthosis nigricans: correlations with insulin resistance and risk factors for cardiovascular disease

Acanthosis nigricans (AN) is linked to obesity and insulin resistance. Major adipokines such as leptin, adiponectin, and resistin are known to be dysregulated in obesity and are key players in the pathogenesis of metabolic syndrome. This study was conducted to assess serum levels of the major adipokines leptin, adiponectin, and resistin, and to study their correlations with the state of insulin resistance and other risk factors for cardiovascular disease (CVD) among AN patients. A total of 115 adult subjects were included in the study; 52 of these had benign acquired AN, and 63 (control subjects) were without AN. Thirty-three of the control group were obese, and 30 were healthy subjects of normal weight. Body mass index (BMI), blood pressure, lipid profile, fasting blood glucose, fasting insulin, serum leptin, adiponectin, and resistin were assessed in all subjects. We found significant differences between AN patients and obese controls in serum levels of leptin (30.02±15.14ng/ml vs. 21.07±7.92ng/ml; P=0.002), adiponectin (5.55±2.89μg/l vs. 9.02±2.33μg/ml; P=0.00001), and resistin (20.88±3.97ng/ml vs. 16.82±4.36ng/ml; P=0.00003). Significant positive correlations were found between serum leptin and homeostasis model assessment (HOMA) value, insulin, glucose, BMI, cholesterol, and low-density lipoprotein. There were also significant negative correlations between adiponectin and HOMA value, insulin, BMI, cholesterol, and leptin among AN patients. Acanthosis nigricans is a likely forerunner of the finding of metabolic syndrome. High serum leptin and resistin and low serum adiponectin may increase the risk for CVD among AN patients.

Independent associations of low 25 hydroxy vitamin D and high parathyroid hormonal levels with nonalcoholic fatty liver disease in Asian Indians residing in north India

ObjectiveWe analysed the associations of 25 hydroxy vitamin D [25(OH) D] and parathyroid hormone (PTH) levels with clinical, anthropometric, biochemical and body composition parameters in Asian Indians with nonalcoholic fatty liver disease (NAFLD). MethodsIn this case–control study, 162 cases and 173 age and sex matched controls were recruited. Clinical, anthropometric, biochemical parameters and liver ultrasound were done. Percentage body fat (%BF), lean body mass and bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DXA). Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR), serum 25(OH) D, calcium and PTH levels were measured. ResultsSubjects with NAFLD had lower serum 25(OH) D (19.4 ± 8.5 vs. 27.8 ± 9.4 ng/ml, p = 0.0001) and higher serum PTH (54.9 ± 19.5 vs.41.5 ± 18.3 pg/ml, p = 0.0001) levels as compared to controls. We observed significantly high values of systolic blood pressure (p = 0.002), waist circumference (p = 0.05), serum triglycerides (p = 0.002), total cholesterol (p = 0.002), alanine transaminase (p = 0.05), fasting insulin (p = 0.02) and HOMA-IR (p = 0.03) in the lowest 25(OH) D quartile. Multivariable-logistic regression showed that low serum 25(OH) D [OR (95%CI): 4.46 (2.58–7.72), p = 0.0001] and high PTH [OR (95%CI): 2.21 (1.50–3.30), p = 0.0001] level were independently associated with NAFLD. ConclusionLow serum 25(OH) D and high PTH levels were independently associated with the presence of NAFLD in Asian Indians residing in north India.

Two-hour insulinemia after oral glucose overload and women at risk of pregnancy-induced hypertensive disorders

Objective: Pregnant women with impaired insulin sensitivity are at risk for developing pregnancy-induced hypertensive disorders (PIHD). We analyzed glucose and insulin circulating levels throughout a 2-h oral 75 g glucose tolerance test in pregnant women, and related the 2-h insulinemias to PIHD prevalence. Methods: Pregnant women (gestational week 24–28) were submitted to a glucose overload, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolite levels, the homeostasis model assessment (HOMA) values and the glucose to insulin ratio (G:Ir) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Results: Women with normal fasting glycemia, insulinemia and HOMA values, G:Ir and 2 h-glycemia but whose 2 h-insulinemia was higher than 215.25 pM were at greater risk for developing late pregnancy hypertension and preeclampsia compared to women of similar characteristics but whose 2 h-insulinemias were lower than 215.25 pM. Conclusion: 2-h insulinemias higher than 215.25 pM after a 75 g glucose overload could be highly indicative of women at increased risk of developing PIHD.

Impairment of pancreatic β‐cell function by chronic intermittent hypoxia

What is the central question of this study? Periodic decreases in arterial blood O2 or chronic intermittent hypoxia (CIH) is a hallmark feature of sleep apnoea patients. Despite a large body of clinical evidence linking sleep disordered breathing with apnoeas to diabetes, the causal relationships between CIH and β-cell function and the underlying molecular mechanisms have not been established. What is the main finding and its importance? In a rodent model, we show that mitochondrial oxidative stress generated by CIH leads to pancreatic β-cell dysfunction manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing and impaired glucose-stimulated insulin secretion. The results of the present study provide evidence for direct effects of CIH on β-cell function, which may be an underlying molecular mechanism contributing to the development of type 2 diabetes among sleep apnoea patients. Breathing disorders with recurrent apnoea produce periodic decreases in arterial blood O2, i.e. chronic intermittent hypoxia (CIH). Recurrent apnoea patients and CIH-exposed rodents exhibit several co-morbidities, including diabetes. However, the effects of CIH on pancreatic β-cell function are not known. In the present study, we investigated pancreatic β-cell function in C57BL6 mice exposed to 30 days of CIH. Compared with control animals, the CIH-exposed mice exhibited elevated levels of fasting plasma insulin but comparable glucose levels and higher homeostasis model assessment, indicating insulin resistance. Pancreatic β-cell morphology was unaltered in CIH-exposed mice. Insulin content was decreased in CIH-exposed β-cells, and this effect was associated with increased proinsulin levels. The mRNA and protein levels of the enzyme prohormone convertase 1, which converts proinsulin to insulin, were downregulated in CIH-treated islets. More importantly, glucose-stimulated insulin secretion was impaired in CIH-exposed mice and in isolated islets. Mitochondrial levels of reactive oxygen species (ROS) were elevated in CIH-exposed pancreatic islets. Treatment of mice with mito-tempol, a scavenger of mitochondrial ROS, during exposure to CIH prevented the augmented insulin secretion and restored the proinsulin and homeostasis model assessment values to control levels. These results demonstrate that CIH leads to pancreatic β-cell dysfunction, manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing, impaired glucose-stimulated insulin secretion and increased mitochondrial ROS, which mediate the effects of CIH on pancreatic β-cell function.

Genetic Variation in the Patatin-Like Phospholipase Domain-Containing Protein-3 (PNPLA-3) Gene in Asian Indians with Nonalcoholic Fatty Liver Disease

The association of the rs738409 polymorphism of patatin-like phospholipase-3 (PNPLA3) with nonalcoholic fatty liver disease (NAFLD) has been suggested in other populations, but not in Asian Indians. We investigated the association of the rs738409 polymorphism of PNPLA3 with clinical, anthropometric, and biochemical profiles in Asian Indians with NAFLD. In this case-control study, 162 cases and 173 controls were recruited. Abdominal ultrasound, clinical, anthropometry, and biochemical profiles were determined. Fasting insulin levels and values for homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Polymerase chain reaction and restriction fragment length polymorphism of the PNPLA3 gene were performed. The associations of this polymorphism with clinical, anthropometric, and biochemical profiles were investigated. A higher frequency of C/G and G/G genotypes of the rs738409 polymorphism was obtained in cases as compared to controls (P=0.04), and as a consequence the frequency of the minor allele G was significantly higher in cases (P=0.003). In this study, the G allele was associated with significantly higher fasting insulin (P=0.002), HOMA-IR (P=0.05), alanine transaminase (P=0.003), and aspartate transaminase (P=0.04) values only in cases, but not in the controls. The values of serum triglycerides and total cholesterol were slightly higher in cases with G/C+G/G genotypes but statistically not significant (P>0.05). Using a multivariate logistic regression model after adjusting for age, sex, body mass index, and fasting insulin, subjects with the G/G genotype showed higher risk of NAFLD [odds ratio (OR), 1.98, 95% confidence interval (CI) 1.43-2.73, P=0.04). The relationships of the rs738409 polymorphism with the metabolic parameters were not significant after adjustment for multiple comparisons. Asian Indians in north India carrying the allele rs738490 of PNPLA3 is predispose to develop NAFLD.

Vitamin D and Insulin Resistance in Non-Diabetic Women's Interagency HIV Study Participants

We explored the relationship between vitamin D levels and insulin resistance (IR) among 1082 nondiabetic (754 HIV-infected) women enrolled in the Women's Interagency HIV study (WIHS), a large and well-established cohort of HIV infected and uninfected women in the US. Vitamin D levels 20-29 ng/mL were considered insufficient and <20 ng/mL deficient. IR was estimated using the homeostasis model assessment (HOMA) and a clinically significant cut-off ≥2.6 was used for HOMA-IR. In the unadjusted analysis, women who were vitamin D insufficient or deficient were 1.62 (95% CI: 1.01-2.61, p=0.05) and 1.70 (95% CI: 1.11-2.60, p=0.02) times more likely to have HOMA values≥2.6 compared to women with sufficient vitamin D. The association did not remain significant after adjustment for factors associated with IR. Among the 754 HIV-infected women, current PI use (OR 1.61, 95% CI: 1.13-2.28, p=0.008) remained independently associated with HOMA ≥2.6 while vitamin D insufficiency (OR 1.80, 95% CI: 0.99-3.27, p=0.05) was marginally associated with HOMA ≥2.6 after adjustment. Ethnicity, body mass index, smoking status, and hepatitis C status were independently associated with insulin resistance in HIV-infected and uninfected women. We found a marginally significant association between vitamin D insufficiency and insulin resistance among nondiabetic HIV-infected WIHS women.