Lean body mass, interleukin 18, and metabolic syndrome in apparently healthy Chinese

Objective

We aimed to investigate how lean body mass is related to circulating Interleukin 18 (IL-18) and its association with metabolic syndrome (MetS) among apparently healthy Chinese.

Methods

A population-based sample of 1059 Chinese men and women aged 35–54 years was used to measure plasma IL-18, glucose, insulin, lipid profile, inflammatory markers and high-molecular-weight (HMW)-adiponectin. Fat mass index (FMI) and lean mass index (LMI) were measured by dual-energy X-ray absorptiometry. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results

Circulating IL-18 was positively correlated with LMI after adjustment for FMI (correlation coefficient = 0.11, P<0.001). The association with the MetS (odds ratio 3.43, 95% confidence interval 2.01–5.85) was substantially higher in the highest than the lowest quartile of IL-18 after multiple adjustments including body mass index. In the stratified multivariable regression analyses, the positive association between IL-18 and MetS was independent of tertiles of FMI, inflammatory markers and HMW-adiponectin, but significantly interacted with tertile of LMI (P for interaction = 0.010).

Conclusion

Elevated plasma IL-18 was associated with higher MetS prevalence in apparently healthy Chinese, independent of traditional risk factors, FMI, inflammatory markers and HMW-adiponectin. More studies are needed to clarify the role of lean mass in IL-18 secretion and its associated cardio-metabolic disorders.     

Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk.

Objective

To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects.

Design

Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.

Results

Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.

Conclusions

We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00429195","term_id":"NCT00429195"}}NCT00429195     

Snoring, inflammatory markers, adipokines and metabolic syndrome in apparently healthy Chinese

Objective

Chronic low-grade inflammation and adipokines dysregulation are linked to mechanisms underscoring the pathogenesis of obesity-related metabolic disorders. Little is known about roles of these cytokines on the association between snoring and metabolic syndrome (MetS). We aimed to investigate whether a cluster of cytokines are related to snoring frequency and its association with MetS in apparently healthy Chinese.

Methods

Current analyses used a population-based sample including 1059 Shanghai residents aged 35–54 years. Self-reported snoring frequency was classified as never, occasionally and regularly. Fasting plasma glucose, lipid profile, insulin, C-reactive protein, interleukin-6, interleukin-18, lipopolysaccharide binding protein, high-molecular-weight adiponectin and leptin were measured. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results

Overweight/obese subjects had significantly higher prevalence of regular snorers than their normal-weight counterparts (34.8% vs. 11.5%, P<0.001). Regular snoring was associated with unfavorable profile of inflammatory markers and adipokines. However, those associations were abolished after adjustment for body mass index (BMI) or waist circumference. The MetS risk (multivariate-adjusted odds ratio 5.41, 95% confidence interval 3.72–7.88) was substantially higher in regular snorers compared with non-snorers. Controlling for BMI remarkably attenuated the association (2.03, 1.26–3.26), while adjusting for inflammatory markers and adipokines showed little effects.

Conclusion

Frequent snoring was associated with an elevated MetS risk independent of lifestyle factors, adiposity, inflammatory markers and adipokines in apparently healthy Chinese. Whether snoring pattern is an economic and no-invasive indicator for screening high-risk persons needs to be addressed prospectively.     

Effects of body fat on the associations of high-molecular-weight adiponectin, leptin and soluble leptin receptor with metabolic syndrome in Chinese

Background

Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations.

Methods

Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans.

Results

HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile  = 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile  = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile  = 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association.

Conclusions

HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively.     

Sedentary behavior is not associated with cardiometabolic risk in adults with abdominal obesity

Objective

The primary aim of this study was to determine whether time spent in sedentary behaviors (SED) was associated with 2-hour glucose and insulin resistance in adults with abdominal obesity. We also examined the association between light physical activity (LPA) and sporadic (accumulated in bouts <10 minutes in duration) moderate-to-vigorous physical activity (MVPA) with glucose metabolism.

Methods

Participants were 135 inactive, abdominally obese adults recruited from Kingston, Canada. SED and physical activity were determined by accelerometry over 7 days and summarized as SED (accelerometer counts/min <100), LPA (counts/min 100–1951), and MVPA (counts/min ≥1952). A 75 g oral glucose tolerance test was used to ascertain 2-hour glucose; the homeostasis model of assessment was used to determine insulin resistance (HOMA-IR); lipid, lipoproteins and blood pressure were determined using standard protocols. Secondary analyses considered the association between SED and physical activity with other cardiometabolic risk factors.

Results

Participants spent 627.2±82.9 min/d in SED, 289.0±91.7 min/d in LPA and 19.2±13.5 min/d in MVPA. Neither SED nor the physical activity variables were associated with 2-hour glucose or HOMA-IR (p>0.05). In secondary analyses, SED was not associated with any cardiometabolic risk factor (p>0.1); with the exception of blood pressure (p<0.05), LPA was not associated with any cardiometabolic risk factor (p>0.1); and MVPA was independently associated with total cholesterol and triglycerides (p<0.05).

Conclusions

Objectively measured SED was not associated with 2-hr glucose or HOMA-IR. Our findings also suggest that the accumulation of LPA and sporadic MVPA is not associated with glucose metabolism in adults with abdominal obesity.     

Associations between Serum Apelin-12 Levels and Obesity-Related Markers in Chinese Children

Objective

To investigate possible correlations between apelin-12 levels and obesity in children in China and associations between apelin-12 and obesity-related markers, including lipids, insulin sensitivity and insulin resistance index (HOMA-IR).

Methods

Forty-eight obese and forty non-obese age- and gender-matched Chinese children were enrolled between June 2008 and June 2009. Mean age was 10.42±2.03 and 10.86±2.23 years in obesity and control groups, respectively. Main outcome measures were apelin-12, BMI, lipids, glucose and insulin. HOMA-IR was calculated for all subjects.

Results

All obesity group subjects had significantly higher total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), insulin levels and HOMA-IR (all P<0.05). In separate analyses, obese girls had significantly higher LDL-C, insulin and HOMA-IR than controls, and obese boys had significantly higher TC, TG, insulin and HOMA-IR than controls (all P<0.05). Apelin-12 levels were significantly higher in obese girls compared to controls (P = 0.024), and correlated positively with TG in all obese subjects. Among obese girls, apelin-12 levels correlated positively with TG, insulin and HOMA-IR after adjusting for age and BMI. In all boys (obese and controls) apelin-12 was positively associated with fasting plasma glucose (FPG). No significant correlations were found in either group between apelin-12 levels and other characteristics after adjusting for age, sex, and BMI.

Conclusions

Apelin-12 levels are significantly higher in obese vs. non-obese girls in China and correlate significantly with obesity-related markers insulin, HOMA-IR, and TG. Increased apelin-12 levels may be involved in the pathological mechanism of childhood obesity.     

The Association of Cysteine with Obesity, Inflammatory Cytokines and Insulin Resistance in Hispanic Children and Adolescents

Context

Plasma total cysteine (tCys) independently relates to fat mass in adults. Dietary cyst(e)ine promotes adiposity and decreases glucose tolerance in some rodent models, but alleviates insulin resistance in others.

Objective

To investigate whether the association of tCys with body fat extends to children at particular risk of obesity, and whether tCys is associated with insulin resistance and obesity-associated inflammation.

Methods

We explored the cross-sectional relations of fasting plasma tCys and related metabolites with body composition measured by dual-energy X-ray absorptiometry in 984 Hispanic children and adolescents aged 4–19 years from the Viva La Familia Study. Linear and logistic regression and dose-response curves were used to evaluate relations of tCys with obesity, insulin resistance and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP).

Results

tCys, methionine and total homocysteine (tHcy) increased with age. Upper tCys quartile was independently associated with a 5-fold increased risk of obesity (95% CI 3.5–8.0, P<0.001), and 2-fold risk of insulin resistance (95% CI: 1.6-5.0, P<0.001; adjusted for body fat%). Within the overweight/obese subgroup, but not in normal-weight children, tCys accounted for 9% of the variability in body fat% (partial r = 0.30, P<0.001; adjusted for age and gender). tCys correlated positively with serum non-esterified fatty acids and leptin, partly independent of body fat, but was not associated with serum IL-6, TNF-α or MCP-1. A positive correlation with CRP disappeared after adjustment for BMI.

Conclusion

tCys is independently associated with obesity and insulin resistance in Hispanic children and adolescents, highlighting a previously underappreciated link between the sulfur amino acid metabolic pathway and obesity and cardiometabolic risk.     

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

Objective

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM.

Measurements

Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively.

Results

Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM.

Conclusions

Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.     

Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children

Objective

Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children.

Research Design and Methods

We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage.

Results

The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity.

Conclusions

Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis.     

Are Risk Factors Associated with Outcomes in Pancreatic Cancer?

Background

The development of pancreatic cancer is a process in which genes interact with environmental factors. We performed this study to determine the effects of the ABO blood group, obesity, diabetes mellitus, metabolic syndrome (MetS), smoking, alcohol consumption and hepatitis B viral (HBV) infection on patient survival.

Methods

A total of 488 patients with pancreatic cancer were evaluated.

Result

Patients who presented as chronic carriers of HBV infection were younger at disease onset (p = 0.001) and more predominantly male (p = 0.020) than those never exposed to HBV. Patients with MetS had later disease staging (p = 0.000) and a lower degree of pathological differentiation (p = 0.008) than those without MetS. In a univariate analysis, the ABO blood group, smoking and alcohol consumption were not associated with overall survival. HBsAg–positivity and elevated fasting plasma glucose were significantly associated with unfavorable survival though not in the multivariate analysis. The presence of MetS (HR: 1.541, 95% CI: 1.095–2.169, p = 0.013), age ≥65, an elevated CA19–9 baseline level, TNM staging, the type of surgery, the degree of differentiation and chemotherapy were independently associated with overall survival.

Conclusion

We report, for the first time, that patients with chronic HBV infection may represent a special subtype of pancreatic cancer, who have a younger age of disease onset and male dominancy. Patients with MetS had later disease staging and a poorer histological grade. Patients with MetS demonstrated significantly poorer survival.     

Insulin Resistance and Risk of Incident Cardiovascular Events in Adults without Diabetes: Meta-Analysis

Background

Glucose, insulin and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) are markers of insulin resistance. The objective of this study is to compare fasting glucose, fasting insulin concentrations and HOMA-IR in strength of association with incident cardiovascular disease.

Methods

We searched the PubMed, MEDLINE, EMBASE, Web of Science, ScienceDirect and Cochrane Library databases from inception to March, 2011, and screened reference lists. Cohort studies or nested case-control studies that investigated the association between fasting glucose, fasting insulin or HOMA-IR and incident cardiovascular disease, were eligible. Two investigators independently performed the article selection, data extraction and risk of bias assessment. Cardiovascular endpoints were coronary heart disease (CHD), stroke or combined cardiovascular disease. We used fixed and random-effect meta-analyses to calculate the pooled relative risk for CHD, stroke and combined cardiovascular disease, comparing high to low concentrations of glucose, insulin or HOMA-IR. Study heterogeneity was calculated with the I² statistic. To enable a comparison between cardiovascular disease risks for glucose, insulin and HOMA-IR, we calculated pooled relative risks per increase of one standard deviation.

Results

We included 65 studies (involving 516,325 participants) in this meta-analysis. In a random-effect meta-analysis the pooled relative risk of CHD (95% CI; I²) comparing high to low concentrations was 1.52 (1.31, 1.76; 62.4%) for glucose, 1.12 (0.92, 1.37; 41.0%) for insulin and 1.64 (1.35, 2.00; 0%) for HOMA-IR. The pooled relative risk of CHD per one standard deviation increase was 1.21 (1.13, 1.30; 64.9%) for glucose, 1.04 (0.96, 1.12; 43.0%) for insulin and 1.46 (1.26, 1.69; 0.0%) for HOMA-IR.

Conclusions

The relative risk of cardiovascular disease was higher for an increase of one standard deviation in HOMA-IR compared to an increase of one standard deviation in fasting glucose or fasting insulin concentration. It may be useful to add HOMA-IR to a cardiovascular risk prediction model.     

Adiponectin gene polymorphism is selectively associated with the concomitant presence of metabolic syndrome and essential hypertension

Objective

Cardiovascular risk increases with the presence of both metabolic syndrome (MetS) and hypertension (HTN). Although the adiponectin (ADIPOQ) gene has been reported to be involved in MetS, its association with HTN remained undetermined. This study aimed to investigate the association of ADIPOQ gene with the phenotypes of HTN and MetS.

Methods

A total of 962 participants from 302 families from the Taiwan young-onset hypertension genetic study were enrolled. Plasma adiponectin were measured, and association analysis was conducted by using GEE regression-based method. Another study, of 1448 unrelated participants, was conducted to replicate the association between ADIPOQ gene and variable phenotypes of MetS with or without HTN.

Results

Among 962 subjects from family samples, the lowest plasma adiponectin value was observed in MetS with HTN component (9.3±0.47 µg/ml) compared with hypertensives (13.4±0.74 µg /ml) or MetS without HTN (11.9±0.60 µg/ml, P<0.05). The SNP rs1501299 (G276T) in ADIPOQ gene was found associated with the presence of HTN in MetS (odds ratio for GG+GT vs. TT = 2.46; 95% CI: 1.14-5.3, p = 0.02), but not rs2241766 (T45G). No association of ADIPOQ gene with HTN alone or MetS without HTN was observed. The significant association of the SNP rs1501299 (G276T) with the phenotype of presence of HTN in MetS was confirmed (odds ratio for GG+GT vs. TT = 2.15; 95% CI: 1.1–4.3) in the replication study.

Conclusions

ADIPOQ genetic variants were selectively and specifically associated with the concomitant presence of MetS and HTN, suggesting potential genetic linkage between MetS and HTN.     

Whole-Body and Hepatic Insulin Resistance in Obese Children

Background

Insulin resistance may be assessed as whole body or hepatic.

Objective

To study factors associated with both types of insulin resistance.

Methods

Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound.

Results

The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother''s BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver.

Conclusion

In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.     

Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease

Objective

Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.

Research Design and Methods

By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs) which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D), central obesity, and WHO-defined metabolic syndrome (MetS).

Results

273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05) to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.

Conclusions

Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.     

Causal Relationship between Adiponectin and Metabolic Traits: A Mendelian Randomization Study in a Multiethnic Population

Background

Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.

Objectives

We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.

Methods

Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes.

Results

Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P<0.002). The rs266729 minor G allele was associated with lower adiponectin and higher HOMA-IR (P = 0.004 and 0.003, respectively). The association between rs266729 SNP and HOMA-IR was no longer significant after adjustment for adiponectin concentration (P = 0.10). The rs266729 SNP was associated with HOMA-IR to an extent that exceeded its effect on adiponectin level (0.15 SD 95% C.I. [0.06, 0.24], P<0.001). There was no significant interaction between rs266729 SNP and ethnicity on adiponectin or HOMA-IR. In contrast, the SNP rs1260326 in GCKR was associated with HOMA-IR (P<0.001), but not with adiponectin level (P = 0.67).

Conclusion

The association of the functional promoter polymorphism rs266729 with lower serum adiponectin and increased insulin resistance in diverse ethnic groups may suggest a causal relationship between adiponectin level and insulin resistance.     

Short-Term Overfeeding Increases Circulating Adiponectin Independent of Obesity Status

Background

Adiponectin is an adipose tissue derived hormone which strengthens insulin sensitivity. However, there is little data available regarding the influence of a positive energy challenge (PEC) on circulating adiponectin and the role of obesity status on this response.

Objective

The purpose of this study was to investigate how circulating adiponectin will respond to a short-term PEC and whether or not this response will differ among normal-weight(NW), overweight(OW) and obese(OB).

Design

We examined adiponectin among 64 young men (19-29 yr) before and after a 7-day overfeeding (70% above normal energy requirements). The relationship between adiponectin and obesity related phenotypes including; weight, percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), body mass index (BMI), total cholesterol, HDLc, LDLc, glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were analyzed before and after overfeeding.

Results

Analysis of variance (ANOVA) and partial correlations were used to compute the effect of overfeeding on adiponectin and its association with adiposity measurements, respectively. Circulating Adiponectin levels significantly increased after the 7-day overfeeding in all three adiposity groups. Moreover, adiponectin at baseline was not significantly different among NW, OW and OB subjects defined by either %BF or BMI. Baseline adiponectin was negatively correlated with weight and BMI for the entire cohort and %TF, glucose, insulin and HOMA-IR in OB. However, after controlling for insulin resistance the correlation of adiponectin with weight, BMI and %TF were nullified.

Conclusion

Our study provides evidence that the protective response of adiponectin is preserved during a PEC regardless of adiposity. Baseline adiponectin level is not directly associated with obesity status and weight gain in response to short-term overfeeding. However, the significant increase of adiponectin in response to overfeeding indicates the physiological potential for adiponectin to attenuate insulin resistance during the development of obesity.     

Association between Cardiac Autonomic Function, Oxidative Stress and Inflammatory Response in Impaired Fasting Glucose Subjects: Cross-Sectional Study

Background

The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects.

Subjects and Methods

Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman’s rank correlation using SPSS 13.0.

Results

The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC.

Conclusion

There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.     

Adipose Tissue CIDEA Is Associated,Independently of Weight Variation,to Change in Insulin Resistance during a Longitudinal Weight Control Dietary Program in Obese Individuals

Aim

Weight loss reduces risk factors associated with obesity. However, long-term metabolic improvement remains a challenge. We investigated quantitative gene expression of subcutaneous adipose tissue in obese individuals and its relationship with low calorie diet and long term weight maintenance induced changes in insulin resistance.

Research Design

Three hundred eleven overweight and obese individuals followed a dietary protocol consisting of an 8-week low calorie diet followed by a 6-month ad libitum weight-maintenance diet. Individuals were clustered according to insulin resistance trajectories assessed using homeostasis model assessment of insulin resistance (HOMA-IR) index. Adipose tissue mRNA levels of 267 genes selected for regulation according to obesity, metabolic status and response to dieting was assessed using high throughput RT-qPCR. A combination of discriminant analyses was used to identify genes with regulation according to insulin resistance trajectories. Partial correlation was used to control for change in body mass index.

Results

Three different HOMA-IR profile groups were determined. HOMA-IR improved during low calorie diet in the 3 groups. At the end of the 6-month follow-up, groups A and B had reduced HOMA-IR by 50%. In group C, HOMA-IR had returned to baseline values. Genes were differentially expressed in the adipose tissue of individuals according to groups but a single gene, CIDEA, was common to all phases of the dietary intervention. Changes in adipose tissue CIDEA mRNA levels paralleled variations in insulin sensitivity independently of change in body mass index. Overall, CIDEA was up-regulated in adipose tissue of individuals with successful long term insulin resistance relapse and not in adipose tissue of unsuccessful individuals.

Conclusion

The concomitant change in adipose tissue CIDEA mRNA levels and insulin sensitivity suggests a beneficial role of adipose tissue CIDEA in long term glucose homeostasis, independently of weight variation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00390637","term_id":"NCT00390637"}}NCT00390637     

Chronic Kidney Disease in Non-Diabetic Older Adults: Associated Roles of the Metabolic Syndrome,Inflammation, and Insulin Resistance

Background

The aims of the study were to examine the association between CKD and the metabolic syndrome (MetS) and its components in older adults. We also explored two possible pathways linking the metabolic syndrome with CKD: inflammation as measured by high sensitivity C-Reactive Protein (hsCRP) and insulin resistance as measured by HOMA-IR.

Methods

Community-dwelling non-diabetic 70+ adults from the Einstein Aging Study participated in the study. We defined CKD as eGFR below 60mL/min/1.73m². MetS was defined according to recent guidelines from the National Cholesterol Education Program. Binary logistic regressions were used to assess the association between the metabolic syndrome, its components and CKD with adjustments for demographics, HOMA-IR and hsCRP.

Results

Of 616 participants (mean age = 79.3 years, 65.5% female), 25% had MetS and 26.5% had CKD. Participants with CKD had a significantly higher prevalence of the MetS than individuals without CKD (34.4% vs. 24.3%). Binary logistic regression models showed that CKD was associated with MetS (OR = 1.72, 95%CI = 1.13–2.61). The association was unaltered by adjustment for hsCRP but altered by adjustment for HOMA-IR. As the number of MetS components increased the relative odds of CKD also increased. None of the individual components was independently associated with CKD.

Conclusion

MetS is associated with CKD in non-diabetic older adults. Results showed that as the number of MetS components increased so did the odds for CKD. HOMA-IR seems to be in the casual pathway linking MetS to CKD.