Lower Adiponectin Levels Research Articles

A Pilot Plant-Based Dietary Intervention in Overweight and Obese Patients with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma- the Nutrition Prevention (NUTRIVENTION) Study

A Pilot Plant-Based Dietary Intervention in Overweight and Obese Patients with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma- the Nutrition Prevention (NUTRIVENTION) Study

RELATIONSHIP BETWEEN ADIPONECTIN AND MYOCARDIAL INFARCTION AMONG DIABETIC PATIENTS

Adiponectin (AD) is an adipocyte-specific secretory protein that is highly expressed in adipose tissue. AD levels are decreased in patients with cardiovascular diseases and type 2 diabetes (DM). This study aimed to analyze the relationship between low levels of adiponectin, diabetes and myocardial infarction. A systematic review was conducted following the PRISMA guidelines. Papers were selected searching PubMed/Medline database in July 2021 using the terms [adiponectin] AND [diabetes] AND [myocardial infarction]. The inclusion criteria were limited to observational studies that evaluated the association between adiponectin index in myocardial infarction among diabetic patients. There were no language or publication date restrictions.Among the 130 papers initially identified, 49 were eligible for this review. AD, inhibits liver gluconeogenesis, displays anti-atherogenic and anti-inflammatory properties and promotes peripheral insulin sensitivity. Lower levels of AD are related to a higher risk of myocardial infarction and a worse prognosis in patients with coronary artery disease. Favorable effects of AD are associated with maintained ischemia-induced angiogenesis, decreased myocyte death, decreased hypertrophic response, reduced interstitial fibrosis and attenuated inflammatory response. It has been suggested that high molecular weight AD is more important for vascular protection. Nevertheless, it is unknown if higher levels of AD are associated with a reduced risk for coronary heart disease and myocardial infarction among diabetic individuals.Although the adiponectin´s pattern of cardioprotection is well stablished, it is still unclear if higher levels are associated with reduced risk of coronary heart disease and myocardial infarction among diabetic individuals.

Hyperinsulinemic-Euglycemic Clamp Strengthens the Insulin Resistance in Nonclassical Congenital Adrenal Hyperplasia.

Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency. Cross-sectional study at university hospital outpatient clinics. NC-CAH patients (25 females, 6 males; 24 ± 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls. At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid-3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m²/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m2/day). The NC-CAH patients presented lower Mffm than controls (31 ± 20 vs 55 ± 23µmol/min-1/kg-1, P = 0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r = -0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels. Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH.

Genome-Wide Association Study on Adiponectin-Mediated Suppression of HDL-C Levels in Taiwanese Individuals Identifies Functional Haplotypes in CDH13

CDH13 encodes T-cadherin, which is expressed in the vasculature and cardiac myocytes and is the receptor for hexameric and high-molecular-weight adiponectin. The CDH13 region is the most pivotal locus associated with adiponectin level. Mediation analysis is a method to explore the effect of a third variable, it is assumed that the magnitude of the relationship between the independent and dependent variables will be reduced by statistical adjustment for a third variable. In addition, mediation can further occur in the case when the mediator acts as a pathway-suppressor variable that means a suppression effect may be suggested if the statistical removal of a mediation effect could increase the magnitude of the relationship between the independent and dependent variables. Here, we aimed to explore the suppression effect in a genome-wide association study, and investigate possible mechanisms that may link adiponectin to CDH13 variants and high-density lipoprotein cholesterol (HDL-C). Genome-wide association data for adiponectin and HDL-C were accessible for 2349 Taiwan-biobank participants. The mediation analysis was conducted with the CDH13 lead single nucleotide polymorphism (SNP) rs4783244. The cloned constructs of CDH13 haplotypes (GG and TT) identified from the rs4783244 G/T and rs12051272 G/T SNPs were transiently expressed in HEK293T cells and investigated using the luciferase reporter assay. Genome-wide association analysis showed that HDL-C is significantly associated with variants in CDH13 after adjusting for the adiponectin level. The lead SNP rs4783244 was significantly associated with lower adiponectin levels and exhibited a suppression effect on HDL-C when adiponectin was included as a third factor in the mediation analysis. Luciferase reporter assay results further demonstrated that the GG haplotype increased enhancer activity, whereas the haplotype TT significantly reduced the activity of this enhancer. We present the first evidence of the suppressive role of adiponectin in the genome-wide association between CDH13 and HDL-C. CDH13 may increase the HDL-C levels, and its expression is suppressed by adiponectin.

Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.

Associations between adverse home environments and appetite hormones, adipokines, and adiposity among Chilean adolescents.

Little is known regarding the relationship between adverse home environments and hormones important in regulation of appetite and their impact on obesity in children and adolescents. In this study, we examined the impact of socioeconomic economic status, family stress and maternal depressive symptoms on appetite hormones, adipokines and adiposity. To determine whether adverse home environments in childhood and adolescence relate to adiposity in adolescence and disruptions in appetite hormones and adipokines, specifically lower levels of adiponectin and ghrelin and elevated levels of leptin and orexin. Adversity in the home (maternal depressive symptoms, family stress, socioeconomic disadvantage) was measured in the households of 593 Chilean youth at age 10 years (52.3% male) and in 606 youth at 16 years. At 16 years, participants provided fasting blood samples for assessment of adipokines and appetite hormones. Waist-to-height ratio was used to assess central adiposity. Correlational analyses examined associations between continuous levels of adversity in childhood and adolescence and appetite hormones and adiposity in adolescence. Multinomial logistic regressions compared hormone levels by tertiles of adversity. Participants were 52% male, with average age at the 16 years hormone assessment being 16.8 (n=606, SD=0.26). Those with highest maternal depression at age 10 had lower adiponectin OR=0.95 [95% CI: 0.91, 0.99], p=0.005) and ghrelin levels (OR=0.98 [95% CI: 0.98, 1.00), p=0.022) than those in the lowest maternal depression group at age 16. Those with the highest family stress at 16 years had lower adiponectin levels (OR=0.93 [95% CI: 0.89, 0.98), p=0.004) and higher central adiposity (OR=1.05 [1.01, 1.08], p=0.009) than the lowest family stress group. There were no significant associations found between socioeconomic status at either 10 or 16 years and appetite hormones. Results add new evidence regarding the relationship between household adversity to appetite hormones and adipokines, with the most consistent results for adiponectin. Current findings suggest that the relationship between home environment and adipokines and appetite hormones may play a role in altered adiposity in children and adolescents.

Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2

Individuals infected with SARS-CoV-2 who also display hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality. Nevertheless, the pathophysiological mechanism of hyperglycemia in COVID-19 remains poorly characterized. Here, we show that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates. A screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin. Moreover, we show that SARS-CoV-2 can infect adipocytes. Together these data suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.

Plasminogen Activator Inhibitor-1 and Adiponectin Are Associated With Metabolic Syndrome Components.

We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components. This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III. Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065-1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610-0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044-1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519-0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS. PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.

Potential role of green tea extract and epigallocatechin gallate in preventing bisphenol A-induced metabolic disorders in rats: Biochemical and molecular evidence

BackgroundBisphenol A (BPA) is an artificial chemical widely used in the production of polycarbonate plastics and epoxy resins. Accumulating evidence indicates that BPA exposure is associated with metabolic disorders. The beneficial effects of green tea and epigallocatechin gallate (EGCG), major catechin present in green tea, on alleviating BPA-induced metabolic disorders have been shown in various studies. PurposeProtective effects of green tea extract and EGCG on BPA-induced metabolic disorders and possible underlying mechanisms were investigated. MethodsRats were randomly divided into control, green tea extract (50 and 100 mg/kg, IP), EGCG (20 and 40 mg/kg, IP), BPA (10 mg/kg, gavage), BPA plus green tea extract (25, 50, and 100 mg/kg, IP), BPA plus EGCG (10, 20, and 40 mg/kg, IP), and BPA plus vitamin E (200 IU/kg, IP). After two months, body weight, blood pressure, biochemical blood tests, hepatic malondialdehyde (MDA), and glutathione (GSH) were assessed. By enzyme-linked immunosorbent assay, serum levels of insulin, leptin, adiponectin, TNFα, and IL-6, and by western blotting, hepatic insulin signaling (IRS-1, PI3K, Akt) were measured. ResultsBPA increased body weight, blood pressure, and MDA, decreased GSH, elevated serum levels of low-density lipoprotein cholesterol, total cholesterol, triglyceride, glucose, insulin, leptin, TNFα, IL-6, and liver enzymes including alanine aminotransferase and alkaline phosphatase, and lowered high-density lipoprotein cholesterol and adiponectin levels. In western blot, decreased phosphorylation of IRS-1, PI3K, and Akt was obtained. Administration of green tea extract, EGCG, or vitamin E with BPA reduced the detrimental effects of BPA. ConclusionThese findings indicate that green tea extract and EGCG can be effective in preventing or reducing metabolic disorders induced by BPA linked to their antioxidant and anti-inflammatory activity, regulating the metabolism of lipids, and improving insulin signaling pathways.

The role of adipocytokines and endothelial dysfunction with irritable bowel syndrome associated with obesity

The article contains the analysis of results concerning investigation of adipocytokines content and endothelial dysfunction in 97 patients with irritable bowel syndrome associated with obesity. The blood serum was examined for the content of adipocytokines (leptin, adiponectin, resistin), stable nitrogen monoxide metabolites (nitrites/nitrates), endothelin-1, intercellular adhesion molecule 1 (ICAM-1), and the number of circulating endothelial cells (CEC). Patients with IBS associated with obesity and prevailing diarrhea are found to develop a prominent imbalance of adipocytokines which is manifested in high levels of leptin and resisin and low level of adiponectin in the blood serum. Endothelial dysfunction evidenced by a high level of endothelin-1, the number of circulating endothelial cells, general NO and intercellular adhesion molecules 1, is characteristic for patients with IBS associated with obesity and prevailing diarrhea.

High frequency and long persistency of ballooning hepatocyte were associated with glucose intolerance in patients with severe obesity

Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance—demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test—and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.

Vascular Function and Distribution of Adiponectin Isomers during Puberty in Children and Adolescents with Obesity

Introduction: Youth with obesity have abnormal vascular function that relates to the anti-atherogenic adipose-derived hormone, adiponectin. The distribution of adiponectin isomers changes during normal puberty, but there are no data in relation to vascular function. We aimed to evaluate vascular function, adiponectin, and its isomers longitudinally in peri-pubertal youth with obesity and controls. Methods: The study is a cohort longitudinal study involving 30 children and adolescents with obesity (body mass index [BMI] z-score 2.31 ± 0.24; age 12.8 ± 3 years, 17 male participants) and 28 age-/sex-matched healthy controls (12.8 ± 3 years, 14 male participants). Vascular function (flow-mediated dilatation [FMD], glyceryl trinitrate-mediated dilatation [GTN]), total adiponectin and isomers, and laboratory and clinical variables were assessed at 0, 18, and 36 months. Results: FMD and GTN were stable during puberty in both groups, remaining consistently lower in obese children (p = 0.02, p < 0.001). The change in total (p = 0.02) and high-molecular weight (HMW) (p = 0.02) adiponectin differed between the groups: falling in controls by the end of puberty but not falling further during puberty in obesity. In obesity, impaired GTN was associated longitudinally with lower total (B = 7.85, p = 0.006) and HMW (B = 3.72, p = 0.03) adiponectin. In controls, more favourable GTN was longitudinally associated with a lower BMI z-score (B = −3.04, p = 0.027) and lower waist circumference (B = −0.35, p = 0.009). Conclusions: Vascular dysfunction and lower levels of adiponectin are associated in children and adolescents with obesity during puberty and do not deteriorate further. Healthy children’s better vascular function, within the normal range, is associated with a lower BMI z-score and waist circumference.

Altered immunometabolism in adipose tissue: A major contributor to the ageing process?

Altered immunometabolism in adipose tissue: A major contributor to the ageing process?

A Novel Automated Immunoassay Platform to Evaluate the Association of Adiponectin and Leptin Levels with Breast Cancer Risk

Simple SummaryAdiponectin and leptin are adipokines secreted by the adipose tissue that have been associated with several chronic diseases including cancer. We compared two methods for their measurement and investigated their association with breast cancer. We measured adiponectin and leptin with the automated ELLA platform and a manual commercially available enzyme-linked immunosorbent assay (ELISA) kit on serum samples of women enrolled in two international breast cancer prevention trials. We found a good concordance between the two methods and our results support the association of low adiponectin levels with breast cancer, irrespective of the method used. The take-home message is that ELLA is a very robust platform that represents a step forward for the future use of adipokines, along with other biomarkers, in clinical cancer risk assessment and prevention. Its use should be taken into account whenever biomarkers should be measured in a large cohort of patients for clinical validation or cancer association studies.Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing–Bablok regression and Bland–Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, p = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.

Association between Adiponectin and Insulin Resistance among Sudanese Males with Type 2 Diabetes Mellitus

Background: Adiponectin is associated with improved systemic insulin sensitivity and profound positive effects in adipose tissue, such as increased mitochondrial density in adipocytes, reducing adipocyte size, and effective esterification of free fatty acids on lipid storage The factor performs forward transcriptional regulation. Diabetes and its complications are considered to be one of the main causes of morbidity and mortality worldwide. Aims and objectives: The aim of this study was to correlate serum levels of adiponectin with insulin resistance in Sudanese males' type 2 diabetes mellitus. Design and Methods: A case-control community-based study carried out among 126 patients with T2DM as cases group (mean ages 45.2±5.4 years); and 126 normal healthy individuals as controls group (mean ages 44.7±5.4 years as) in Aldaraga Diabetic Center, Wad Medani, Gezira State, Sudan. About Five mL of fasting venous blood was obtained from all participants. HbA1c, FPG, FPI, serum Adiponectin, and (HOMA)- IR were analyzed. SPSS (v 20.0) was used for data analysis. Results: The mean of serum adiponectin in the cases group (3.03±0.90µg/ml) was lower than the control group (6.02±4.24µg/ml) giving highly significant differences -between them (P=value ≤ 0.000). HbA1c and Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) differed significantly between the two groups (P-value ≤ 0.000). Serum adiponectin concentrations correlated significantly negative with HOMA IR (r = -0.149, P-value = 0.002). Conclusion: We concluded that low plasma adiponectin level was predictive of future development of Insulin resistance in Sudanese males.

Insulin resistance and potential modulators of ovarian reserve in young reproductive-aged women with obesity and type 1 diabetes

Introduction Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmed trait d’union. We evaluated the relationship between IR and an established ovarian reserve biomarker such as anti-mullerian hormone (AMH) together with other potential modulators of ovarian physiology (adiponectin and kisspeptin) in young reproductive-aged group women with obesity and type 1 diabetes (T1D). Patients and methods We recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively. Results adiponectin and kisspeptin levels were significantly different into groups (p ≤ .001), whereas AMH levels were not. Adiponectin values were higher in controls compared to patients with obesity (p < .001) and T1D (p = .02). Kisspeptin levels were lower in controls compared to patients with obesity (p = .001), without reaching statistical significance when compared to T1D (p = .06). IR was associated with lower adiponectin and higher kisspeptin levels (p < .001 and p = .02, respectively), but not with AMH. Conclusions IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.

Influence of Single Nucleotide Polymorphism of ENPP1 and ADIPOQ on Insulin Resistance and Obesity: A Case-Control Study in a Javanese Population.

Single nucleotide polymorphisms (SNPs) in obesity-related genes, such as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) and adiponectin (ADIPOQ), potentially increase the risk of insulin resistance, the most common metabolic dysregulation related to obesity. We investigated the association of ENPP1 SNP K121Q (rs1044498) with insulin resistance and ADIPOQ SNP + 267G > T (rs1501299) with circulating adiponectin levels in a case–control study involving 55 obese and 55 lean Javanese people residing in Yogyakarta, Indonesia. Allele frequency was determined by a chi squared test or Fisher’s exact test with an expected value less than 0.05. Odds ratios and 95% confidence intervals were estimated by regression logistic analysis. The presence of the Q121 allele of ENPP1 resulted in significantly higher fasting glucose, fasting insulin levels, and HOMA-IR, as compared to homozygous K121 carriers. The risk of insulin resistance was elevated in obese individuals carrying Q121 instead of homozygous K121. Adiponectin level was significantly lower in the obese group as compared to the lean group. Obese individuals carrying homozygous protective alleles (TT) of ADIPOQ tended to have lower adiponectin levels as compared to GT and GG carriers, however, we did not find statistically significant effects of the +276G > T SNP of the ADIPOQ gene on the plasma adiponectin levels or on the development of obesity.

Galectin-3/adiponectin as a new biological indicator for assessing the risk of type 2 diabetes: a cross-sectional study in a community population.

Objective: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance.Methods: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models.Results: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21–5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models.Conclusions: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.

Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial.

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-L-carnitine (ALC) and metformin plus pioglitazone. A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500mg, 15mg, and 1500mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500mg, 15mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group. We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889 .

Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.