High Molecular Weight Adiponectin Levels Research Articles

Plasma adiponectin levels, ADIPOQ variants, and incidence of type 2 diabetes: A nested case-control study.

To clarify the associations between plasma adiponectin levels and ADIPOQ variants with type 2 diabetes incidence in a general Japanese population. We conducted a case-control study nested within the Japan Public Health Center-based Prospective Study. We measured plasma adiponectin levels and genotyped +45T>G (rs2241766) and +276G>T (rs1501299) in the ADIPOQ gene among 417 incident diabetes cases and 1197 control subjects matched by age, sex, and area. After potential confounding factor adjustment, the multivariable-adjusted diabetes odds ratios (ORs) were 0.59 (95% confidence interval [CI]: 0.51-0.68) and 0.68 (95% CI: 0.60-0.78) per 1 standard deviation increment in the log-transformed levels of total- and high-molecular-weight (HMW) adiponectin levels, respectively. However, the ADIPOQ variants were not significantly associated with plasma adiponectin levels (for total adiponectin, +45 P=0.15 and +276 P=0.08) and diabetes risk (+45 P=0.70 and +276 P=0.72) under the additive genetic model. Our prospective findings suggest that both total and HMW adiponectin levels are strongly and inversely associated with diabetes risk after adjustment for potential confounding factors; however, the ADIPOQ variants +45 and +276 are not associated with adiponectin levels and diabetes risk in the general Japanese population.

CDH13 Genetic Polymorphisms, Adiponectin and Ischemic Stroke: a Chinese Family-based Sib-pair Study

ObjectiveTo understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors. MethodsWe recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model. ResultsIn individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = −0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = −0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = −0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001). ConclusionCDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.

Sustained High Levels of Both Total and High Molecular Weight Adiponectin in Plasma during the Convalescent Phase of Haemorrhagic Fever with Renal Syndrome Are Associated with Disease Severity.

Haemorrhagic fever with renal syndrome (HFRS) is characterised by an uncontrolled immune response that causes vascular leakage. Adiponectin (APN) is an adipocytokine involved in prorevascularisation and immunomodulation. To investigate the possible effects of APN in the pathogenesis of HFRS, total and high molecular weight (HMW) APN levels in the plasma of patients with HFRS were quantified using enzyme-linked immunosorbent assay (ELISA). Compared with those in healthy controls, the plasma total and HMW APN levels in patients were elevated to different degrees from the fever onset and remained high at the convalescent phase. Consistent with these results, western blot analysis additionally showed that low molecular weight (LMW), middle molecular weight (MMW), and HMW APN levels were all elevated and contributed to the elevation of the total APN level. Importantly, sustained high levels of total and HMW APN at the convalescent phase were significantly higher in patients with critical disease than those in patients with mild or moderate disease. Moreover, total and HMW APN levels negatively correlated with white blood cell count and positively correlated with platelet count and serum albumin level. These results may provide insights into understanding the roles of total and HMW APN in the pathogenesis of HFRS.

Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis.

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production.

A method comparison of total and HMW adiponectin: HMW/total adiponectin ratio varies versus total adiponectin, independent of clinical condition

BackgroundTotal and high-molecular-weight (HMW) adiponectin have been associated with endocrine and cardiovascular pathology. As no gold standard is available, the discussion about biological relevance of isoforms is complicated. In our study we perform a method comparison between two commercially available assays measuring HMW and total adiponectin, in various patient groups, thus contributing further to this discussion. MethodsWe determined levels of HMW and total adiponectin using assays by Lumipulse® and Millipore® respectively, in 126 patients with different clinical characteristics (n=29 healthy volunteers, n=22 dialysis patients, n=25 elderly with body mass index (BMI) <21kg/m2, n=25 elderly with BMI 30–35kg/m2, n=26 children). ResultsThe Passing & Bablock regression analysis resulted in HMW adiponectinLUMIPULSE∗0.5−0.9=total adiponectinMILLIPORE, albeit with significant deviation from linearity (p<0.001). Pearson's correlation was R=0.987 (p=0.000). No significant differences between patient groups were observed (p=0.190). ConclusionsThe HMW/total adiponectin ratio varies with total adiponectin concentration independent of clinical conditions studied. Our results imply that total and HMW adiponectin have similar utility when assessing adiponectin levels in blood, as the ratio is independent of clinical condition.

A cross-sectional study of the association between adipokine levels and bone mineral density according to obesity and menopausal status in Korean women.

Results regarding the association between adipokine levels and bone mineral density (BMD) have been inconsistent; the effects of sex, menopause, and central obesity remain unknown. We evaluated the association between serum leptin, adiponectin, and high-molecular-weight (HMW) adiponectin levels and BMD according to menopause and central obesity status in Korean women. This cross-sectional study comprised 255 women undergoing examinations at the CHA Bundang Medical Center. Participants were divided according to menopause, and central obesity status. We measured serum adipokine levels and BMD using an enzyme-linked immunosorbent assay and dual-energy X-ray absorptiometry, respectively. After adjusting for age, body mass index, alkaline phosphatase levels and the Homeostasis Model Assessment index, leptin levels were negatively associated with non-vertebral BMD (total hip, β=-0.576, P=0.006; femoral neck, β=-0.608, P=0.007) in postmenopausal women without central obesity. Among women without central obesity, HMW adiponectin levels were positively associated with total hip BMD (β=0.240, P=0.010) in premenopausal women but negatively associated with BMD (lumbar, β=-0.436, P=0.012; femoral neck, β=-0.468, P=0.007) in postmenopausal women. Thus, the association between adipokine levels and BMD varies according to the menopause and central obesity status.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg-1·day-1 BBR (HF+LBBR group) and 380 mg·kg-1·day-1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Short-term caloric restriction in db/db mice improves myocardial function and increases high molecular weight (HMW) adiponectin

BackgroundObesity and metabolic syndrome lead to the development of metabolic heart disease (MHD) that is characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and increased mitochondrial ROS. Caloric restriction (CR) is a nutritional intervention that protects against obesity, diabetes, and cardiovascular disease. Healthy adipose tissue is cardioprotective via releasing adipokines such as adiponectin. We tested the hypothesis that CR can ameliorate MHD and it is associated with improved adipose tissue function as reflected by increased circulating levels of high molecular weight (HMW) adiponectin and AMP-activated protein kinase (AMPK) in db/db mice. MethodsGenetically obese db/db and lean db/+ male mice were fed either ad libitum or subjected to 30% CR for 5weeks. At the end of the study period, echocardiography was carried out to assess diastolic function. Blood, heart, and epididymal fat pads were harvested for mitochondrial study, ELISA, and Western blot analyses. ResultsCR reversed the development of LVH, prevented diastolic dysfunction, and decreased cardiac mitochondrial H2O2 in db/db (vs. ad lib) mice. These beneficial effects on the heart were associated with increased circulating level of HMW adiponectin. Furthermore, CR increased AMPK and eNOS activation in white adipose tissue of db/db mice, but not in the heart. ConclusionsThese findings indicate that even short-term CR protects the heart from MHD. Whether the beneficial effects of CR on the heart could be related to the improved adipose tissue function warrants future investigation.

High molecular weight adiponectin and lipid profile in the type-2 diabetes mellitus-Mets

Background: Dyslipidemia is a major component of the metabolic syndrome (Mets) and a strong risk factor for the development of cardiovascular disease. High Molecular Weight (HMW) Adiponectin is an adipocyte-derived hormone that enhances insulin sensitivity. It plays an important role in glucose and lipid metabolism. Plasma HMW adiponectin level is decreased in patients with type 2 diabetes. The effects of dyslipidemia on plasma HMW adiponectin levels in human subjects have not yet been studied. Aim: To investigate the correlation between HMW adiponectin level and lipid profile in the type-2 diabetes mellitus (T2DM)-Mets patients. Method: This is a cross sectional study with T2DM-Mets patients who came to the outpatient clinic of Soetomo Hospital in Surabaya during January 2010 to December 2012. Subjects met the inclusion and exclusion criteria were measured their HMW adiponectin level in plasma using ELISA method. Index lipid profile measured were serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), LDL/HDL ratio and TG/HDL ratio. The study was approved by the local Research Ethics Committee and subjects gave written informed consent. Results: Forty T2DM-Mets patients consisted of 16 (40%) males and 24 (60%) females who met inclusion and exclusion criteria were enrolled in this study. Their mean of age was 51 ± 5.2 years old, duration of illness was 16.49 ± 23.4 months, HMW adiponectin level was 2,195.6 ± 4.6 ng/mL, A1C level was 8.52 ± 0.9%, BMI was 26.62 ± 4.5 kg/m2, LDL-C level was 148.35 ± 31.1 mg/dL, triglyceride level was 173.00 ± 100.2 mg/ dL, HDL-C level was 48.15 ± 8.93 mg/dL, LDL/HDL ratio was 3.15 ± 0.7, and TG/HDL ratio was 3.78 ± 2.4. Spearman’s correlation analysis showed that HMW adiponectin level was significantly correlated with triglyceride level and TG/HDL ratio (p = 0.009; r = −0.407 and p = 0.014; r = −0.387, respectively). However, no significant correlation found with HDL-C, LDL-C, and LDL/HDL ratio. Conclusion: Triglyceride cholesterol and TG/HDL ratio are correlated with HMW adiponectin level in this T2DM-MetS population.

High Molecular Weight Adiponectin Levels are Neither Influenced by Adiponectin Polymorphisms Nor Associated with Insulin Resistance in Mixed-ancestry Hyperglycemic Subjects from South Africa.

SummaryBackgroundHigh molecular weight (HMW) adiponectin has antiatherogenic, antiinflammatory and antidiabetic properties and these effects have been linked to its effect on high density lipoprotein cholesterol (HDL-c). Single nucleotide polymorphisms (SNPs) in the adiponectin gene influence adiponectin levels. We examined the relationship between HMW-adiponectin levels and cardiometabolic traits in normo- and hyperglycemic mixed ancestry South Africans and correlated these levels to two common polymorphisms.MethodsHMW-adiponectin was determined in 101 subjects from the Cape Town Bellville South community-based study on a mixed ancestry population. Comparisons were made between individuals with normo- and hyperglycemia. Two common SNPs, ADIPOQ SNPs rs17300539 and rs266729, known to affect adiponectin levels were also tested for. Levels of HMW-adiponectin were then correlated with cardiometabolic traits in all groups.ResultsLevels of HMW-adiponectin were not significantly different in the normo- and hyperglycemic groups (median 11.6 vs. 10.5 μg/mL, p=0.3060) and in men and women (8.44 vs. 11.34 μg/mL, p=0.67). ADIPOQ SNPs rs17300539 and rs266729 did not influence levels of HMW-adiponectin. Robust correlation analyses revealed a significant positive correlation between HMW-adiponectin and HDL-c (r=0.45; 95%CI: 0.27–0.59), similarly in normo- and hyperglycemic participants (p > 0.99). This association was substantially attenuated in robust linear regressions adjusted for age, gender and adiposity.ConclusionsAdiponectin levels in this population were not determined by the commonest SNPs of the adiponectin gene, were unaffected by glycemic status; but were significantly correlated with HDL-c levels. Previous studies have attributed some of the beneficial effects of adiponectin to its effect on HDL-c.

Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR−/−) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA.

Association between insulin resistance and estrogen in sexual precocity of obese children.

The aim of the study was to examine the association between sexual precocity and high-molecular weight (HMW)-adiponectin and investigate the correlation of insulin resistance and estrogen levels in obese children. In total, 60 obese children (30 boys and 30 girls) with sexual precocity were included in group A, 60 obese children (30 boys and 30 girls) without sexual precocity were included in group B, and 60 average weight children (30 boys and 30 girls) were included in group C. The levels of HMW adiponectin, fasting blood glucose, fasting insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured. The results showed that the HMW-adiponectin level of group A was the lowest and that of group C was the highest. The difference was statistically significant (P<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) and estradiol levels of group A were significantly higher than those of group B, and group B was higher than that of group C. LH peak and testosterone levels of group A were the lowest while those of group C were the highest. The differences were statistically significant (P<0.05). A subgroup analysis showed that the above results were more significant in girls. The Pearson correlation analysis revealed that the level of HMW-adiponectin was negatively correlated with HOMA-IR and estradiol (P<0.05), and positively correlated with the LH peak (P<0.05). In conclusion, sexual precocity of obese children may be associated with insulin resistance, and the link may be HMW-adiponectin.

Changes in Serum High-Molecular-Weight Adiponectin Levels in Critically Ill Children with Systemic Inflammatory Response Syndrome

Background: The aim of the study was to evaluate the effect of the systemic inflammatory response syndrome (SIRS) on serum high-molecular-weight adiponectin (HMWA) levels. Method: Twelve children with SIRS were enrolled in this study at the intensive care unit (ICU). Twelve age and sex matched healthy subjects were selected as controls. Serum HMWA, interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) levels were determined after 2 hours and 24 hours, and on the day of discharge which was on the average 9.4 days after ICU admission. Results: 2 hours after admission to the ICU, the patients had significantly decreased serum HMWA levels compared with healthy controls (P &lt; .001). 24 hours after the admission, the patients did not have any significant changes in their HMWA levels, however on the day of discharge, on average 9.4 days after hospital admission, a significant increase was observed (P &lt; .05). After the treatment, there was a decrease in serum PCT, IL-6 and CRP levels. The only variable that was decreased 24 hours after the ICU admission was PCT (P &lt; .05). A negative correlation was found between serum HMWA and PCT levels, and between HMWA and CRP (P &lt; .05 and P &lt; .01), however no correlation was found between HMWA and IL-6. Conclusion: In SIRS we observed a marked reduction in serum HMWA concentrations and a profound increase in IL-6, PCT, and CRP levels. A significant relationship between serum HMWA and PCR and CRP levels was evident.

Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren.

The secreted hepatokine fetuin-A emerges as an independent predictor of type 2 diabetes in adulthood. The overall aims of this study were: (1) to investigate the associations of fetuin-A with adiposity and insulin resistance, as well as its relationship with adipokines, in prepubertal children, and, (2) to evaluate whether, in prepubertal obesity, serum fetuin-A levels may either change or predict the responsiveness to an educational-based weight excess reduction program. We studied 200 prepubertal children (boys/girls: 89/111; Tanner stage 1; age: 5-13 years), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 100 individuals were lean (boys/girls: 57/43) and 100 obese (boys/girls: 54/46). A subset of 53 obese individuals (boys/girls: 28/25; age: 6-12 years) were also evaluated after a weight excess reduction program. Serum fetuin-A, leptin, total and high molecular weight adiponectin levels, as well as homeostasis model assessment of insulin resistance were assessed. When compared with lean, obese children exhibited higher ( p < 0.0001) fetuin-A concentrations, without differences between sex. Fetuin-A was positively associated with adiposity, homeostasis model assessment of insulin resistance, and leptin levels. In multivariate analysis, the associations between fetuin-A and leptin or homeostasis model assessment of insulin resistance lost the significance after adjustment for BMI Z-score, which, in turn, represented an independent determinant of fetuin-A (R 2adj 0.327; p < 0.0001). Notably, after weight excess reduction program, fetuin-A levels dropped ( p < 0.0001 vs. basal). Interestingly, no significant differences of fetuin-A concentrations between responders and no responders were found. In prepubertal children, fetuin-A represents an early marker of adiposity, and its reduction after lifestyle intervention may partly contribute to the beneficial effects of weight excess reduction program.

Effects of Delayed Sample Processing on Determination of Total and High Molecular Weight (HMW) Adiponectin in Serum and Plasma: A Pilot Study

&lt;p&gt;Adiponectin is a beneficial adipocyte-secreted hormone, which circulates in a variety of multimeric forms termed low and high molecular weight (LMW/HMW). Effectiveness of clinical therapeutic trials which target adiponectin rely on accurate determination of circulating total and HMW adiponectin levels but the accuracy may be influenced by variations in sample handling processes. The aim of this pilot study was to investigate the effects of delayed processing of blood samples on the concentration of total and HMW adiponectin.&lt;/p&gt;&lt;p&gt;Materials and Methods: Fasting blood samples were collected for analysis of total and HMW adiponectin concentrations in EDTA plasma and serum from eight healthy participants. Samples were centrifuged post 15 min storage at 4&lt;sup&gt;o&lt;/sup&gt;C as the comparative ‘ideal’ method or after up to 72 h of refrigerated storage or 6 h at room temperature. Total and HMW adiponectin concentrations were measured by ELISA.&lt;/p&gt;&lt;p&gt;Results: Under ideal handling conditions measurements of total and HMW adiponectin concentrations were significantly higher in serum than in plasma (mean difference: -1.3 µg/mL [95% CI: -1.6, -1.0], p&amp;lt;0.001; and, -0.6 µg/mL [95% CI: -0.7, -0.5], p&amp;lt;0.001, respectively). Storage of blood samples at 4&lt;sup&gt;o&lt;/sup&gt;C for 72 h resulted in significant reductions in concentration of total adiponectin in serum (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) and HMW adiponectin in plasma (mean difference: -0.6 µg/mL [95%CI: -0.9, -0.2], p=0.007), compared with ideal conditions. Further analysis of serum samples showed a significant decrease in total adiponectin concentration after 6 h storage at 4&lt;sup&gt;o&lt;/sup&gt;C (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) compared with ideal conditions.&lt;/p&gt;&lt;p&gt;Conclusions: Delayed processing of samples may have differential effects on the concentration of total and HMW adiponectin in serum or plasma. Larger studies are warranted for clinical intervention trials.&lt;/p&gt;

Emerging Cardiovascular Disease Biomarkers and Incident Diabetes Mellitus Risk in Statin-Treated Patients With Coronary Artery Disease (from the Treating to New Targets [TNT] Study)

Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80mg) versus low (10mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n= 253), 101 patients developed DM during the median follow-up of 4.9years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.

Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies.

Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of −0.334 μg/ml (95% CI, −0.465 to −0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of −0.502 μg/ml (95% CI, −0.957 to −0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.

Longitudinal changes in adiponectin multimer levels in preterm infants

BackgroundPreterm infants have altered adiponectin levels at term-equivalent age and have a higher risk of developing components of the metabolic syndrome in later life than term infants. AimsTo investigate the longitudinal changes in adiponectin levels in preterm infants and to compare the levels between term and preterm infants. Study designA cohort study. SubjectsThe study subjects were 43 term infants and 42 preterm infants born at ≤34-week gestation. Outcome measuresSerum levels of total adiponectin (T-Ad) and high-molecular-weight adiponectin (HMW-Ad) were measured in 42 preterm infants at term-, 6month-, and 12month-equivalent ages. Moreover, the levels in 43 term infants investigated previously were reviewed. ResultsIn preterm infants, T-Ad and HMW-Ad levels at the 12month-equivalent age were lower than at the term- and 6month-equivalent ages (all values p<0.001), which was consistent with previous results in term infants. The difference in ratios of HMW-Ad to T-Ad between term and preterm infants continued at the 6month-equivalent age but disappeared at the 12month-equivalent age. Multiple regression analyses revealed that HMW-Ad levels at term-equivalent age were only a significant determinant of the changes in HMW-Ad between the term- and 12month-equivalent ages in preterm infants (p<0.001). ConclusionsThe HMW-Ad levels decline till the 12month-equivalent age in both term and preterm infants. The changes in HMW-Ad level during infancy might be determined at least to a certain degree up to term-equivalent age in preterm infants.

Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes

Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60mgkg−1, i.p.). Animals from exercised groups swam (5 days/week, 90min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-α, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM.

Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes.

Subclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes. Motor and sensory NCV was assessed in individuals with recently diagnosed type 2 (n=352) or type 1 diabetes (n=161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammation-related biomarkers, DSPN and NCV sum scores were estimated using multiple regression models. In type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV. Our results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.