Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy.

This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects. There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-ß, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.

Visualized macrophage dynamics and significance of S100A8 in obese fat.

Chronic low-grade inflammation of adipose tissue plays a crucial role in the pathophysiology of obesity. Immunohistological microscopic analysis in obese fat tissue has demonstrated the infiltration of several immune cells such as macrophages, but dynamics of immune cells have not been fully elucidated and clarified. Here, by using intravital multiphoton imaging technique, to our knowledge for the first time, we analyzed and visualized the inflammatory processes in adipose tissue under high-fat and high-sucrose (HF/HS) diet with lysozyme M-EGFP transgenic (LysM(EGFP)) mice whose EGFP was specifically expressed in the myelomonocytic lineage. Mobility of LysM(EGFP)-positive macrophages was shown to be activated just 5 d after HF/HS diet, when the distinct hypertrophy of adipocytes and the accumulation of macrophages still have not become prominent. Significant increase of S100A8 was detected in mature adipocyte fraction just 5 d after HF/HS diet. Recombinant S100A8 protein stimulated chemotactic migration in vitro and in vivo, as well as induced proinflammatory molecules, both macrophages and adipocytes, such as TNF-α and chemokine (C-C motif) ligand 2. Finally, an antibody against S100A8 efficiently suppressed the HF/HS diet-induced initial inflammatory change, i.e., increased mobilization of adipose LysM(EGFP)-positive macrophages, and ameliorated HF/HS diet-induced insulin resistance. In conclusion, time-lapse intravital multiphoton imaging of adipose tissues identified the very early event exhibiting increased mobility of macrophages, which may be triggered by increased expression of adipose S100A8 and results in progression of chronic inflammation in situ.

Single stimulus fMRI produces a neural individual difference measure for Autism Spectrum Disorder.

Functional magnetic resonance imaging typically makes inferences about neural substrates of cognitive phenomena at the group level. We report the use of a single-stimulus BOLD response in the cingulate cortex that differentiates individual children with autism spectrum disorder from matched typically developing control children with sensitivity and specificity of 63.6% and 73.7% respectively. The approach consists of passive viewing of 'self' and 'other' faces from which an individual difference measure is derived from the BOLD response to the first 'self' image only; the method, penalized logistic regression, requires no averaging over stimulus presentations or individuals. These findings show that single-stimulus fMRI responses can be extracted from individual subjects and used profitably as a neural individual difference measure. The result suggests that single-stimulus fMRI can be developed to produce quantitative neural biomarkers for other developmental disorders and may even be useful in the rapid typing of cognition in healthy individuals.

Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. Mutant AR has been postulated to alter the expression of genes important for mitochondrial function and induce mitochondrial dysfunction. Here, we show that the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), a key regulator of mitochondrial biogenesis, were decreased in mouse and cellular models of SBMA. Treatment with pioglitazone (PG), an activator of PPARγ, improved the viability of the cellular model of SBMA. The oral administration of PG also improved the behavioral and histopathological phenotypes of the transgenic mice. Furthermore, immunohistochemical and biochemical analyses demonstrated that the administration of PG suppressed oxidative stress, nuclear factor-κB (NFκB) signal activation and inflammation both in the spinal cords and skeletal muscles of the SBMA mice. These findings suggest that PG is a promising candidate for the treatment of SBMA.

Clinical significance of visceral adiposity assessed by computed tomography: A Japanese perspective.

Abdominal obesity, rather than total amount of fat, is linked to obesity-related disorders. Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects. In 1983, our group reported techniques for body fat analysis using computed tomography (CT) and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications, such as diabetes, lipid disorders, hypertension and atherosclerosis. Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan. Visceral fat area (VFA) measured in a single slice at L4 level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan. In a large-scale study of a Japanese population, the mean number of obesity-related cardiovascular risk factors (hypertension, low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia, and hyperglycemia) was greater than 1.0 at 100 cm(2) of VFA, irrespective of gender, age and body mass index. Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification, "Hokenshido", correlated with a decrease in the number of obesity-related cardiovascular risk factors. It is important to select the most appropriate subjects from the general population (e.g., non-obese subjects with a cluster of risk factors for the metabolic syndrome) that are most suitable for body weight reduction, with the goal of preventing atherosclerotic cardiovascular diseases.

A pilot three-month sitagliptin treatment increases serum adiponectin level in Japanese patients with type 2 diabetes mellitus--a randomized controlled trial START-J study.

BACKGROUND: The dipeptidyl-peptidase-IV (DPP-4) inhibitors, including sitagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM). Adiponectin, an adipocyte-derived circulating protein, has anti-atherosclerotic and anti-diabetic properties and is effectively elevated in bloodstream by thiazolidinediones, an insulin sensitizer. However, the effect of sitagliptin treatment on serum adiponectin level in T2DM has not fully elucidated in Japanese T2DM patients. The aim of the present study was to examine the effect of sitagliptin treatment on serum adiponectin levels in T2DM subjects. METHODS: Twenty-six consecutive Japanese T2DM outpatients were recruited between April 2011 and March 2013, and randomized into the control (conventional treatment, n = 10) group and sitagliptin treatment group (n = 16). Serum adiponectin was measured by enzyme-linked immunosorbent assay. RESULTS: Indices of glycemic control, such as hemoglobin A1c, glycated albumin, and 1.5-anhydro-D-glucitol, were significantly improved after the three-month treatment in both the control and sitagliptin groups. Serum adiponectin level was significantly increased in sitagliptin group from 6.7 ± 0.8 to 7.4 ± 1.0 µg/mL without change of body mass index (p = 0.034), while serum adiponectin level was not altered in the control group (p = 0.601). CONCLUSION: In Japanese T2DM patients, serum adiponectin level was elevated by three-month treatment with sitagliptin without change of body weight. TRIAL REGISTRATION: UMIN000004721.

Increased serum C1q-binding adiponectin complex to total-adiponectin ratio in men with multi-vessel coronary disease.

BACKGROUND: Adiponectin plays a role as a positive contributor to the stabilization of atherosclerotic plaques. Circulating total adiponectin (Total-APN) levels associates with the number of coronary vessels in men with coronary artery disease (CAD). We recently reported that adiponectin binds to C1q in human blood, and serum C1q-binding adiponectin (C1q-APN) /Total-APN levels are associated with CAD in type 2 diabetic subjects. The present study investigated the relationship between circulating C1q-APN levels and the number of angiographic coronary artery vessel in male subjects. METHODS: The study subjects were 53 male Japanese patients who underwent diagnostic coronary angiography. Blood total adiponectin (Total-APN), high-molecular weight adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assays. RESULTS: Serum C1q-APN/Total-APN ratio significantly increased in subjects with single and multi-vessel coronary diseases (p = 0.029 for trend, the Kruskal-Wallis test). However, serum Total-APN, HMW-APN, C1q-APN and C1q levels did not correlate with number of diseased coronary vessels. CONCLUSION: Serum C1q-APN/Total-APN ratio progressively increases in men with single and multi-vessel coronary disease. TRIAL REGISTRATION: UMIN000002997.

Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice.

Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT-WT) or KO mice (WT-KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT-KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT-KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity.

Adiponectin as a routine clinical biomarker.

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 µg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended.

Accumulation of adiponectin in inflamed adipose tissues of obese mice.

OBJECTIVE: Adipose tissue inflammation plays an important role in the pathogenesis of obesity-associated complications, such as atherosclerosis. Adiponectin secreted from adipocytes has various beneficial effects including anti-inflammatory effect. Obesity often presents with hypoadiponectinemia. However, the mechanism and adiponectin movement in obesity remain uncharacterized. Here we investigated tissue distribution of adiponectin protein in lean and obese mice. METHODS: Adiponectin protein levels were evaluated by enzyme-linked immunosorbent assay and western blotting. Adipose tissues were fractionated into mature adipocyte fraction (MAF) and stromal vascular fraction (SVF). RESULTS: Adiponectin protein was detected not only in MAF but also in SVF, which lacks adiponectin mRNA expression, of adipose tissue remarkably. SVF adiponectin protein level was higher in obese mice than in lean mice. The mechanism of adiponectin accumulation was investigated in adiponectin-deficient (APN-KO) mice after injection of plasma from wild-type mice. These mice showed accumulation of exogenous adiponectin, which derived from wild type mice, in adipose tissues, and the adiponectin was more observed in SVF of diet induced obese APN-KO mice than lean APN-KO mice. Among the adiponectin binding proteins, T-cadherin mRNA and protein levels in SVF of obese mice were remarkably higher than in lean mice. Oxidative stress levels were also significantly higher in SVF of obese mice than lean mice. Mechanistically, H2O2 up-regulated T-cadherin mRNA level in murine macrophages. CONCLUSIONS: The results demonstrated adiponectin targets to adipose SVF of obese mice. These findings should shed a new light on the pathology of adipose tissue inflammation and hypoadiponectinemia of obesity.

Short-term intervention reduces bioelectrical impedance analysis-measured visceral fat in type 2 diabetes mellitus.

In 25 patients with Type 2 diabetes mellitus, the short-term in-hospital calorie restriction combined with moderate exercise reduced visceral fat. The reduction of visceral fat can improve metabolic cardiovascular risk factors, while the reductions in body weight and waist circumference were small and reduction in subcutaneous fat was not significant.

High serum C1q-binding adiponectin levels in male patients with acute coronary syndrome.

BACKGROUND: The complement system is part of the immune system in acute coronary syndrome (ACS). Adiponectin has anti-atherogenic and anti-inflammatory properties. Adiponectin and C1q form a protein complex in blood, and serum C1q binding adiponectin (C1q-APN) can be measured. We investigated the comparative evaluation of serum C1q-APN levels in males with ACS, stable angina pectoris (SAP) versus controls. METHODS: The study subjects were 138 Japanese patients who underwent diagnostic coronary angiography. Blood total adiponectin (Total-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assays. Patients were divided into three groups according to the clinical condition: ACS (n = 78), SAP (n = 41) or normal coronary (NC, n = 19) groups. RESULTS: Serum C1q levels were significantly higher in the ACS group (54.9±1.2 µg/mL) than in the NC group (48.0±2.5 µg/mL). Although serum Total-APN levels were significantly lower in the SAP and ACS groups, compared with the NC group (7.0±0.5, 7.2±0.3, 10.6±2.0 µg/mL, respectively), serum C1q-APN levels were significantly higher in the ACS group than in the NC and SAP groups (112.1±4.1, 66.3±4.4, 65.7±2.9 units/mL, respectively). CONCLUSIONS: Patients with ACS had higher serum C1q-APN levels. TRIAL REGISTRATION: UMIN000002997.

Low serum eicosapentaenoic acid / arachidonic acid ratio in male subjects with visceral obesity.

BACKGROUND: Visceral fat accumulation is caused by over-nutrition and physical inactivity. Excess accumulation of visceral fat associates with atherosclerosis. Polyunsaturated fatty acids have an important role in human nutrition, but imbalance of dietary long-chain polyunsaturated fatty acids, especially low eicosapentaenoic acid (EPA) / arachidonic acid (AA) ratio, is associated with increased risk of cardiovascular disease. The present study investigated the correlation between EPA, docosahexaenoic acid (DHA), AA parameters and clinical features in male subjects. FINDINGS: The study subjects were 134 Japanese with diabetes, hypertension and/or dyslipidemia who underwent measurement of visceral fat area (eVFA) by the bioelectrical impedance method and serum levels of EPA, DHA and AA. EPA/AA ratio correlated positively with age, and negatively with waist circumference and eVFA. Stepwise regression analysis demonstrated that age and eVFA correlated significantly and independently with serum EPA/AA ratio. Serum EPA/AA ratio, but not serum DHA/AA and (EPA+DHA)/AA ratios, was significantly lower in subjects with eVFA ≥100 cm2, compared to those with eVFA <100 cm2 (p=0.049). Subjects with eVFA ≥100 cm2 were significantly more likely to have the metabolic syndrome and history of cardiovascular diseases, compared to those with eVFA <100 cm2 (p<0.001, p=0.028, respectively). CONCLUSIONS: Imbalance of dietary long-chain polyunsaturated fatty acids (low serum EPA/AA ratio) correlated with visceral fat accumulation in male subjects. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000002271.

Correlation of circulating C1q and C1q-binding adiponectin concentrations with aging in males: a preliminary report.

BACKGROUND: Atherosclerosis is an age-related disease. Adiponectin and C1q form a protein complex in human blood, and that serum C1q and C1q-binding adiponectin (C1q-APN) concentrations can be measured. We investigated circulating C1q and C1q-APN levels in Japanese men including elderly men. FINDINGS: The study subjects were 509 Japanese men including elderly men. Serum levels of total adiponectin (Total-APN), high-molecular weight-adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assay. Total-APN, HMW-APN and C1q-APN, but not C1q, correlated significantly and positively with aging (r=0.26, r=0.24, r=0.17, p<0.01, respectively). The HMW-APN/Total-APN ratio correlated significantly and positively with aging (r=0.14, p<0.01). The C1q-APN/Total-APN ratio and C1q-APN/HMW-APN ratio correlated significantly and negatively with aging (r=-0.17, p<0.01, r=-0.12, p=0.01). C1q-APN/C1q correlated significantly and positively with aging (r=0.09, p=0.03). Multiple regression analysis identified age and body mass index as significant determinants of C1q-APN. CONCLUSIONS: The present study demonstrates that serum HMW-APN, C1q-APN, and Total-APN, but not C1q, correlated positively with aging. These preliminary results could form the basis for future research. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000004318.

Serum C1q- binding adiponectin in maintenance hemodialysis patients.

BACKGROUND: Patients on maintenance hemodialysis (HD) have much higher levels of adiponectin (Total-APN). Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We recently reported that C1q-APN/Total-APN ratio rather than Total-APN correlated with atherosclerosis in diabetics. However, the characteristics of C1q-APN in HD patients remain unclear. The preset study investigated the characteristics of the adiponectin parameters including C1q-APN and also to clarify the relationship between various serum adiponectin parameters and atherosclerotic cardiovascular diseases (ACVD) in HD patients. METHODS: The single cross-sectional study subjects were 117 Japanese patients (males/females = 61/56) on regular HD. Blood Total-APN, high molecular weight-adiponectin (HMW-APN), C1q-APN and C1q concentrations were measured by enzyme-linked immunosorbent assays. ACVD were defined as stroke, coronary and peripheral artery diseases, thoracic and abdominal aneurysms. RESULTS: Stepwise regression analysis identified high-density lipoprotein-cholesterol (HDL-C) as the only significant and independent determinant of C1q-APN in males, and duration of HD as the only significant and independent determinant of C1q-APN in females. Stepwise regression analysis identified uric acid, low-density lipoprotein-cholesterol and triglyceride as significant and independent determinants of C1q-APN/Total-APN ratio in males, and leukocyte count and HDL-C as significant and independent determinants of C1q-APN/Total-APN ratio in females. Multiple logistic regression analysis identified inorganic phosphorus and C1q-APN or C1q-APN/C1q ratio as significant determinants of ACVD. CONCLUSIONS: Low serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients. TRIAL REGISTRATION: ClinicalTrials.gov: UMIN http://000004318.

Circulating adiponectin levels and their associated factors in young lean healthy Japanese women.

AIM: The aim of the current study was to investigate circulating adiponectin levels and their associated factors in young lean healthy Japanese women. METHODS: We recruited 82 healthy Japanese women in their twenties and thirties with their body mass index <25 kg/m(2), and performed anthropometric, sphygmomanometric, and laboratory examinations. Laboratory examinations included adiponectin levels, as well as lipid profiles, glucose, hemoglobin A1c, transaminase, and creatinine levels, from which the glomerular filtration rate was estimated (eGFR). RESULTS: The median and interquartile range of circulating adiponectin levels were 8.1 (6.2-10.0) µg/ mL. HDL cholesterol levels and eGFR, but not the other examined clinical parameters, were significantly correlated with log-transformed adiponectin levels; their correlation coefficients were 0.323 (p<0.01) and -0.311 (p<0.01), respectively. Statistical significance was still observed even after adjustment for each other (both p= 0.02). In adjusted models, subjects with HDL cholesterol levels ≥80 mg/dL had 1.3 times higher adiponectin levels than those with 40-60 mg/dL, whereas eGFR ≥110 mL/min/1.73m(2) and 60-90 mL/min/1.73m(2) showed a 1.5-fold difference in adiponectin levels. CONCLUSIONS: Adiponectin levels of young lean healthy Japanese women had significant associations with HDL cholesterol levels and eGFR, even though their HDL cholesterol levels and eGFR were distributed within normal ranges. It seems important to take into account these two variables in evaluating adiponectin levels of these subjects, even if the two variables are within normal ranges.

Correlation between serum C1q-adiponectin/total adiponectin ratio and polyvascular lesions detected by vascular ultrasonography in Japanese type 2 diabetics.

OBJECTIVE: Atherosclerosis is a disease of blood vessels. Adiponectin is a biomarker of atherosclerosis. Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We investigated the relationship between various serum adiponectin parameters and polyvascular atherosclerosis score assessed by vascular ultrasonography, in subjects with type 2 diabetes mellitus (T2DM). METHODS: The study subjects were 108 outpatients with T2DM who underwent evaluation for atherosclerosis by vascular ultrasonography. Polyvascular atherosclerosis score represented the sum of atherosclerotic abnormalities in the aorta, carotid, renal and common iliac arteries. Blood C1q, total-adiponectin (Total-APN), high molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme-linked immunosorbent assays. The estimated visceral fat area (eVFA) was measured by bioelectrical impedance. RESULTS: Polyvascular atherosclerosis score correlated only with the C1q-APN/Total-APN ratio (p=0.018 for trend). There were no significant relationships between various adiponectin parameters and carotid maximum intima-media thickness and ankle-brachial index. Age-, sex-, eVFA-adjusted multiple logistic regression analysis that included the above variables identified serum C1q-APN/Total-APN ratio as the only significant and independent determinant of polyvascular atherosclerosis score. CONCLUSIONS: Serum C1q-APN/Total-APN ratio correlates with atherosclerosis detected by polyvascular vascular ultrasonography, independent of gender and visceral adiposity, in T2DM.

Binding of adiponectin and C1q in human serum, and clinical significance of the measurement of C1q-adiponectin / total adiponectin ratio.

OBJECTIVE: Adiponectin and C1q have similar sequences, exist abundantly in blood, and are produced by adipose tissues. The aim of this study was to examine whether adiponectin and C1q form protein-complex in blood and to know the clinical significance of the C1q-adiponectin (C1q-APN) complex in serum. METHODS: The direct interaction between adiponectin and C1q was investigated by far western blotting and co-immunoprecipitation. The relationship between serum C1q-APN and various clinical features was analyzed in 329 Japanese men who underwent health check-up, including measurements of visceral (VFA) and subcutaneous fat area (SFA) by computed tomography (Victor-J study). RESULTS: Adiponectin bound to C1q in vitro and C1q-APN complex existed in human blood. C1q-APN complexes were identified in high- and middle-molecular weight forms of adiponectin in human serum by gel-filtration chromatography. Stepwise multiple regression analysis identified body mass index, VFA and SFA as significant determinants of serum C1q-APN level. Serum C1q-APN/Total-APN ratio correlated positively with cardiovascular risk factor accumulation in subjects with VFA ≥100 cm(2). CONCLUSIONS: These results indicate that high- and middle-molecular forms of adiponectin partly consist of adiponectin-complex with other proteins including C1q and that the blood C1q-APN/Total-APN ratio may serve as a biomarker of the metabolic syndrome in general male subjects.

Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

High serum C1q-adiponectin/total adiponectin ratio correlates with coronary artery disease in Japanese type 2 diabetics.

OBJECTIVE: Adiponectin, an adipocyte-derived protein, has potential antiatherogenic properties. Low levels of serum total-adiponectin (Total-APN) correlate with diabetes and coronary artery disease (CAD). Adiponectin and C1q form a protein complex in blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We investigated the correlation between C1q-APN and CAD in patients with type 2 diabetes mellitus (T2DM). METHODS: The study subjects were 107 outpatients with T2DM who underwent evaluation for CAD. Blood C1q, Total-APN, high-molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme-linked immunosorbent assays. RESULTS: Serum levels of C1q-APN/Total-APN ratio were higher in patients diagnosed with CAD (10.47±0.59, mean±SEM, n=54) than those without CAD (8.88±0.60, n=53, p=0.0482). Age- and sex-adjusted logistic regression analysis identified serum C1q-APN/Total-APN ratio and hypertension as significant and independent determinants of CAD. A high serum C1q-APN/Total-APN ratio was associated with 3.965-fold increase in CAD prevalence. CONCLUSIONS: High serum C1q-APN/Total-APN ratio correlates with CAD in T2DM.