A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

Platelet count can predict metabolic syndrome in older women.

Platelet count (PC) has been found to be related to the metabolic syndrome (MetS). However, the role of PC on MetS remained unclear. In order to evaluate the relationship between PC and MetS components cross-sectionally and determine the optimal cutoff PCs for predicting the subsequent risk of MetS development with sex specificity, two stages included cross-sectional (stage 1) and prospective (stage 2) cohort study were conducted. Stage 1 involved 10 579 subjects aged ≥60 years, of which 7718 subjects advanced to stage 2 with a mean 3.8 year follow-up were enrolled. The MetS components and PC were determined. The PC cutoffs for higher chances of developing MetS in stage 1 were calculated using receiver operating characteristic (ROC) curve analyses. In stage 2, non-MetS subjects were classified into high-PC (HPC) and low-PC (LPC) groups according to the cutoff values from stage 1. We examined the difference of future MetS incidence and calculated the odds ratio (OR) between these two groups. In stage 1, multiple regression showed that age and triglyceride (both sexes) and waist circumstance and high-density lipoprotein cholesterol (only women) were independently correlated with PC. There was significant difference in the area under the ROC curve (AUC) only of HPC women, which exceeded the standard curve (AUC = 0.542, p < 0.001), with a cutoff PC of 223 × 10(3)/µl. HPC women had an OR of 1.287 (95% confidence interval: 1.135-1.461) of developing MetS after 3.8 years. The Kaplan-Meier curve demonstrated a higher incidence of MetS development in HPC women. In conclusion, our results suggest that PC was associated with MetS with sex effects. Most of the MetS components were independent factors for increasing PC, and the risk for subsequent development of MetS was noted when PC >223 × 10(3)/µl in elderly women.

Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study.

BACKGROUND: Metabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families. METHODS: Non-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components. RESULTS: Among the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16). CONCLUSION: In Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. ( TRIAL REGISTRATION: NCT00260910, ClinicalTrials.gov).

Chinese metabolic syndrome risk score.

BACKGROUND: The metabolic syndrome (MetS) was first proposed to predict the occurrence of cardiovascular disease and type 2 diabetes. However, it is difficult to identify subjects with MetS early. No previous studies designed to develop a predictive model for MetS in the Chinese population exists; this study was designed to fill that gap. METHODS: A middle-aged Chinese cohort of 198 men and 154 women were followed for two years. The binary logistic regression and receiver operation characteristic (ROC) curve were used to develop a predictive model for the future development of MetS. RESULTS: Over two years of follow up, 30 of the 352 subjects (8.52%) without MetS at baseline subsequently developed MetS. Triglycerides (TG) had the highest area under the curve (AUC), while diastolic blood pressure had the lowest. In order to increase the prediction power, MetS components were arranged in the ROC model according to their AUC. After adding waist circumference (WC) to TG (model 1), the AUC was significantly higher than for TG alone. Adding other components into the model did not increase the AUC significantly. A risk score cutoff (0.078) was selected for the best predictive power of model 1 (sensitivity of 76.7%, specificity of 63.4%, with AUC of 76.8%). CONCLUSIONS: These results imply that WC and TG are related to the pathophysiologies of MetS, and model 1 could also be used clinically for screening subjects at high risks for MetS.

Factor analysis of metabolic syndrome using direct measurement of insulin resistance in Chinese with different degrees of glucose tolerance.

BACKGROUND & OBJECTIVE: With the increasing prevalence of type 2 diabetes and cardiovascular disease in Taiwan, the understanding of metabolic syndrome (MetS) becomes more important. The purpose of this study was to investigate the clustering patterns of the risk variables of the MetS with factor analysis (FacAn). METHODS: A total of 564 Chinese individuals with normal glucose tolerance (N, n=345), impaired glucose tolerance (IGT, n=164) or diabetes mellitus (DM, n=55) were enrolled. Insulin resistance was measured by insulin suppression test (IST). The components of MetS such as waist hip ratio (WHR), fasting plasma glucose (FPG), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high density lipoprotein cholesterol (HDLC) and steady state plasma glucose (SSPG) from IST were put into the model of exploratory FacAn. RESULTS: In spite of the minor different loading patterns, three dimensions were identified in the three subgroups; a "blood pressure" dimension, loading with mainly SBP and DBP, an "insulin resistance" dimension, loading mainly with SSPG, and an "adiposity/glucose" dimension loading with TG, WHR or FPG. INTERPRETATION & CONCLUSION: Our results were consistent with different ethnic groups in earlier reports that more than two dimensions were identified and that the MetS is not unified by a single underlying aetiology, i.e., insulin resistance. Longitudinal analysis in this and other populations will be required to validate our findings and to test their generalisability.

Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.

The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis. A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19 ± 0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2296966, rs17849148, and rs3193970 were genotyped and examined. To deal with correlated data of subjects within the same families, the generalized estimating equations approach was applied throughout all association analyses. The GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test. These two SNPs revealed independent associations with age of diabetes onset as well as risk of diabetes at baseline. These findings supported that SORBS1 gene participates in the pathogenesis of diabetes.

Abdominal pain and multi-organ dysfunction syndrome in a young woman.

Thyroid storm is a rare but life-threatening condition caused by exaggerated thyrotoxic manifestations. Untreated thyroid storm is fatal, and the case fatality rate is 21% to 30%. The most important clinical management in thyroid storm is early recognition and treatment. We present the case of a previously healthy young woman in whom suspected gastrointestinal tract sepsis complicated by multi-organ dysfunction syndrome masked the major symptomatology of thyroid storm. This patient highlights the importance of a high clinical suspicion for potentially life-threatening conditions, such as thyroid storm, even in the absence of clinical clues (exophthalmos, lid lag, and goiter) or a history of thyrotoxicosis.

CRP-level-associated polymorphism rs1205 within the CRP gene is associated with 2-hour glucose level: The SAPPHIRe study.

C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P < 0.008). Alleles C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P < 1.2 × 10-6). Allele C at rs3093059 was associated with fasting glucose (ß = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (ß = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.

Rosiglitazone improves insulin sensitivity in nonobese subjects with impaired glucose tolerance: the role of adiponectin and C-reactive protein.

To evaluate the effects of rosiglitazone (ROS) on serum adiponectin and C-reactive protein (CRP) in nonobese subjects with impaired glucose tolerance (IGT), we enrolled 21 patients with body mass index < or =24 kg/m(2) to receive ROS 4 mg daily for 12 weeks. Fifteen age-, sex-, and body mass index-matched healthy subjects were recruited as controls. A 75-g oral glucose tolerance test (OGTT), hemoglobin A(1c), fasting glucose, insulin, C-peptide, lipid profiles, adiponectin, and CRP levels were determined before initiation and at the end of the 12-week ROS treatment. Insulin resistance and beta-cell function were calculated using the homeostasis model assessment method (HOMA-IR and HOMA-beta, respectively). Compared with healthy controls, the ROS-treated subjects had significantly higher glycemic indices, HOMA-IR, CRP, and glucose and insulin concentrations in response to OGTT, and lower HOMA-beta level. After 12 weeks of ROS therapy, the results showed statistically significant changes from baseline in 2-hour plasma glucose during OGTT (9.4 +/- 0.3 vs 8.3 +/- 0.4 mmol/L, P < .05), HOMA-IR (2.6 +/- 0.2 vs 1.9 +/- 0.3, P < .05), HOMA-beta (63.4 +/- 12.5 vs 90.1 +/- 13.0, P < .05), and glucose and insulin concentrations during OGTT in nonobese subjects with IGT. In addition, elevation of serum adiponectin and decrease in CRP levels were significantly found after ROS treatment. Of 21 patients treated with ROS, 5 subjects were converted to normal (converter), 1 progressed to diabetes, and 15 remained in IGT status (nonconverter). There was a significant amelioration in HOMA-IR (-2.10 +/- 1.03 vs -0.07 +/- 0.33, P < .05) without significant changes in adiponectin and CRP levels in converter compared with nonconverter. We conclude that ROS effectively enhanced insulin sensitivity and beta-cell function to improve adiponectin and CRP levels in nonobese patients with IGT. The amelioration of insulin resistance may be a major determinant to predict the conversion of IGT independent of the changes in adiponectin and CRP.

Predicting Glucose Effectiveness in Chinese Participants Using Routine Measurements.

BACKGROUND: Glucose effectiveness (GE) is the capacity of glucose to increase its own uptake and to maintain endogenous hepatic glucose output under basal insulin levels. In addition to decreased insulin sensitivity (IS) and impaired insulin secretion, GE plays a critical role in glucose balance in patients with type 2 diabetes (T2DM). In the study, we developed an equation for predicting GE. METHODS: We enrolled 227 participants with glucose tolerances ranging from normal glucose tolerance to diabetes. Of the participants, 75% (171) participants were randomly assigned to the study group, whose data were used to construct the equation for estimating GE. The remaining 56 participants comprised the validation group. All participants underwent a frequently sampled intravenous glucose tolerance test; IS, GE, and the acute insulin response after the glucose load were determined. RESULTS: Age, triglyceride (TG), and fasting plasma glucose (FPG) were independently correlated with GE and selected for inclusion in multiple linear regression analysis. We constructed the following equation: GE = (29.196 - 0.103 × age - 2.722 × TG - 0.592 × FPG) × 10-3. Using this same equation, we also calculated the GE of the validation group. The calculated GE was significantly correlated with the measured GE (r = 0.430, P = 0.001). CONCLUSIONS: Using the equation based on routine measurements enabled the GE to be predicted with acceptable accuracy (r = 0.430). This method of predicting GE may aid clinicians in further understanding the underlying pathological mechanisms of T2DM.

Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.

Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort.We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff <0.1 to adjust for multiple comparisons. In the Cox regression analysis for hypertension-free survival, a robust sandwich variance estimator was used to deal with the within-family correlations with age at onset of hypertension. Gender, body mass index, and antihypertension medication were adjustment covariates in the Cox regression analysis.In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication.In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension. The biological mechanism of genetic variation associated with blood pressure regulation needs further investigation.

Genome-wide linkage analysis and regional fine mapping identified variants in the RYR3 gene as a novel quantitative trait locus for circulating adiponectin in Chinese population.

Adiponectin is adipocyte-secreted cytokine with potent insulin-sensitizing action in peripheral tissues. The heritability of plasma adiponectin is high in Han Chinese population.To identify genetic loci influencing plasma adiponectin levels in Chinese population, we performed a genome-wide linkage scan in 1949 Chinese participants of the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study and mapped a quantitative trail locus located on chromosome 15 at 31 cM (logarithm of odds = 3.04) with 1-logarithm of odds support interval at 24 to 34 cM. Within this mapped region, we further genotyped a total of 68 single-nucleotide polymorphisms in 12 genes. Association analysis revealed that haplotypes composed of single-nucleotide polymorphisms in the ryanodine receptor 3 (RYR3) gene had strongest association with plasma adiponectin. RYR3 haplotypes were also associated with systolic (P = 0.001) and diastolic (P = 7.1 × 10) blood pressure and high-density lipoprotein cholesterol (P = 1.4 × 10). Furthermore, an inverse relationship between expression of RYR3 and adiponectin was observed in human abdominal adipose tissue. In conclusion, a genome-wide linkage scan and regional association fine-mapping identified variants in the RYR3 gene as a quantitative trail locus for plasma adiponectin levels in Chinese population.

Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes.

BACKGROUND: To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. METHODS: A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. RESULTS: The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. CONCLUSIONS: Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.

Thyrotoxic periodic paralysis: an overview.

Thyrotoxic periodic paralysis (TPP) is a fairly common manifestation of hyperthyroidism in Asian populations, with an incidence of about 1.9% in thyrotoxic patients, but it is rarely diagnosed among Caucasians and blacks in the Western world. The diagnosis often can be made on the basis of the clinical manifestations alone. Sometimes, periodic paralysis precedes hyperthyroidism or occurs in silent hyperthyroidism. As a result, physicians may easily overlook it even when life-threatening hypokalemia is present. The pathophysiology of this disorder is still not well understood. Correction of the thyrotoxic state is the definitive treatment. Potassium supplementation, propranolol, and spironolactone may be helpful both in the acute state and in preventing attacks.

Soluble form of receptor for advanced glycation end products is associated with obesity and metabolic syndrome in adolescents.

The aim of this cross-sectional study was to investigate the relationship between soluble form of receptor for advanced glycation end products (sRAGE), obesity, and metabolic syndrome (MetS) in adolescents. A total of 522 male and 561 female adolescents were enrolled into the final analyses. Anthropometric parameters, blood pressure, blood biochemistry, fasting insulin, and plasma sRAGE levels were measured. In males, sRAGE was significantly and inversely correlated with waist circumference (WC), body mass index (BMI), systolic blood pressure, triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and homeostasis model assessment-insulin resistance (HOMA-IR). Only WC and BMI were significantly and inversely correlated with sRAGE in females. Using linear regression analysis adjusting for age and gender, significant association was found between sRAGE and WC, BMI, TG, LDL-C, and HOMA-IR in adolescents of either gender (P < 0.05). This association was abolished when further adjusting BMI. In addition, sRAGE was significantly and inversely correlated with the increasing number of components of MetS in males (P for trend = 0.006) but not in females (P for trend = 0.422). In conclusion, plasma sRAGE is associated with obesity and MetS among adolescents. BMI may be the most important determinant of sRAGE levels in adolescents.

Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats.

AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (FPV), with intraportal saline plus administration of LA (FPV + LA), with lipopolysaccharide (LPS) infusion (FPLPS), and with LPS infusion plus administration of LA (FPLPS + LA). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal-endotoxemia but not fructose-induced liver and pancreatic abnormalities in a rodent model for metabolic syndrome.

The association of retinol-binding protein 4 with metabolic syndrome and obesity in adolescents: the effects of gender and sex hormones.

OBJECTIVES: Retinol-binding protein 4 (RBP4) has a role in the development of insulin resistance (IR), type 2 diabetes, obesity, and metabolic syndrome among adults. However, data among adolescents are limited, and the effects of gender and sex hormones on RBP4 are not well defined. MATERIALS/METHODS: A total of 1082 adolescents were enrolled and categorized based on their body mass index. Blood samples were collected, and biochemical characteristics, sex hormones, RBP4 concentrations, and IR were determined. RESULTS: Testosterone and estradiol were not directly correlated with RBP4 concentrations in both genders. Multivariate regression analysis revealed that fasting plasma glucose (FPG), triglyceride (TG), and testosterone levels were independently associated with RBP4 concentrations in boys; also, there was a trend of increasing RBP4 levels with the severity of obesity. CONCLUSION: Plasma RBP4 concentrations correlated with obesity and cardiovascular risk factors, predominantly evident in boys. Testosterone, FPG, and TG levels were independent predictors of RBP4 concentrations.

Interleukin-6 receptor gene 48892 A/C polymorphism is associated with metabolic syndrome in female Taiwanese adolescents.

BACKGROUND: This study was to evaluate the relationship between the interleukin-6 receptor (IL-6R) 48892 A/C single-nucleotide polymorphism (SNP) (rs8192284) and the metabolic syndrome (MetS) and its components among young adolescents in Taiwan. METHODS: We enrolled 925 adolescents (451 boys and 474 girls). Modified National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) criteria were applied to define MetS (with age- and gender-specific 90th percentile cutoff point of variables). Subjects had three or more of the following cardiometabolic abnormalities that occur in MetS: high blood pressure, high fasting glucose, high triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), and obesity. The characteristics of the MetS components associated with different alleles and genotypes of the IL-6R rs8192284 SNP were compared. RESULTS: Frequencies of alleles and genotypes of the IL-6R 48892 polymorphism were similar in both sexes. Boys with C-alleles had borderline lower TG levels than A-allele carriers (66.0±30.1 vs. 70.3±34.6 mg/dL, p=0.07). However, girls with C-alleles had higher waist circumference (WC) (68.0±7.9 vs. 67.0±7.7 cm) and lower HDL-C levels (50.7±11.1 vs. 52.2±11.7 g/dL) than A-allele carriers (p=0.05). The prevalence of MetS and its components, high WC and low HDL-C level, were higher in female C-allele carriers (all p<0.05) but not in boys. The odds ratios for high WC, low HDL-C levels, and MetS for female C-allele carriers were 1.54 (95% confidence interval [CI]: 1.01-2.34), 1.49 (95% CI: 1.01-2.18), and 2.19-2.39 (95% CI: 1.15-4.51), respectively, when compared with A-allele carriers. CONCLUSIONS: The IL-6R 48892 A/C polymorphism is associated with high TG and WC, and low HDL-C levels in adolescents. Additionally, there is a gender difference in the incidence of MetS, indicating a possible gene-gender interaction of the IL-6R 48892 A/C polymorphism in MetS among Taiwanese adolescents.

Baseline forced expiratory volume in the first second as an independent predictor of development of the metabolic syndrome.

A growing body of evidence strongly supports associations between reduced lung function and insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The present study was undertaken to explore the possibility that reduced lung function is an independent predictor of development of the metabolic syndrome (MetS) and to investigate potential links between reduced lung function and the MetS. A prospective cohort study of reduced lung function as a predictor of subsequent MetS was conducted using 2-year follow-up data for 450 middle-aged adults lacking the MetS at baseline. Data were obtained from the Taipei MJ Health Screening Centers in Taiwan. The MetS was defined according to the modified Adult Treatment Panel III criteria. Over 2 years of follow-up, 26 of the 450 subjects (5.78%) without the MetS at baseline subsequently developed the syndrome. In multiple logistic regression analysis with adjustments for age, sex, body mass index, cigarette smoking, alcohol consumption, and physical activities, reduced forced expiratory volume in the first second (FEV(1)) at baseline remained a predictor of subsequent MetS (relative risk of 4.644, P = .036 for the third [<2.31 L] vs first [>2.88 L] tertile). In Pearson and partial correlation analyses, white blood cell counts and C-reactive protein concentrations were both found to be significantly and negatively correlated with FEV(1). Lower FEV(1) is concluded to serve as an independent predictor of the MetS. Low-grade systemic inflammation is the possible link between reduced lung function and the MetS.

Genetic variants of human urea transporter-2 are associated with metabolic syndrome in Asian population.

BACKGROUND: A previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort. METHODS: Five HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy-Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study. RESULTS: Among those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9×10(-4)≤p≤0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p=0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p=0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction. CONCLUSION: The results have provided evidence that the HUT2 gene may play a certain role in developing MetS and its related traits in Asian population. Further investigation of the HUT2 gene influencing MetS and its related traits will be warranted.