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High serum adiponectin is associated with anemia development in chronic kidney disease: The results from the KNOW-CKD study.
Kim, H, Yun, HR, Park, S, Jhee, JH, Park, JT, Yoo, TH, Lee, KB, Kim, YH, Sung, SA, Lee, J, et al
Cytokine. 2018;:1-9
Abstract
BACKGROUND Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. METHODS This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of <13.0 and 12.0 g/dL for men and women, respectively. RESULTS Mean patient age was 53.6 ± 12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ± 30.2 mL min-1 1.73 m-2. Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, β = -0.219, P < .001; women, β = -0.09, P = .025). Among 1227 patients without anemia at baseline, 307 newly developed anemia during the follow-up period. In multivariable Cox regression analysis after adjustment of confounders, high adiponectin level was significantly associated with an increased risk of incident anemia (per 1 µg/mL increase, hazard ratio, 1.02; 95% confidence interval 1.01-1.04; P = .001). CONCLUSIONS A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia.
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The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.
Larnkjær, A, Ong, KK, Carlsen, EM, Ejlerskov, KT, Mølgaard, C, Michaelsen, KF
Hormone research in paediatrics. 2018;(1):28-38
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BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin.
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Variants in APOA5 and ADIPOQ Moderate Improvements in Metabolic Syndrome during a One-Year Lifestyle Intervention.
Lowry, DE, Fenwick, PH, Roke, K, Jeejeebhoy, K, Dhaliwal, R, Brauer, P, Royall, D, Tremblay, A, Klein, D, Mutch, DM
Lifestyle genomics. 2018;(2):80-89
Abstract
BACKGROUND Metabolic syndrome (MetS) comprises a cluster of risk factors including central obesity, hypertension, dyslipidemia, and impaired glucose homeostasis. Lifestyle interventions that promote improvements in diet quality and physical activity represent a first line of therapy for MetS. However, varying responses to lifestyle interventions are well documented and may be partially explained by underlying genetic differences. The aim of this study was to investigate if variants in genes previously associated with MetS influence the magnitude of change in MetS risk during a 1-year lifestyle intervention. METHODS The present study used data collected from the Canadian Health Advanced by Nutrition and Graded Exercise study cohort (n = 159 men and women) to investigate the effect of 17 candidate single nucleotide polymorphisms (SNPs) on response to a 1-year lifestyle intervention. Associations between SNPs and the continuous MetS (cMetS) score, as well as individual MetS components, were examined. RESULTS Reductions in cMetS score at both 3 months and 1 year were significantly associated with 2 variants: rs662799 (A/G) in apolipoprotein A5 (APOA5) and rs1501299 (G/T) in adiponectin (ADIPOQ). Individuals carrying a minor T allele in rs1501299 experienced a greater reduction in cMetS score at both 3 months and 1 year, whereas major allele AA homozygotes in rs662799 experienced greater reductions in cMetS score during the intervention. No associations were identified between the aforementioned SNPs and individual components of MetS. Both un-weighted and weighted genetic risk scores (GRS) using these 2 SNPs revealed that individuals carrying none of the risk alleles experienced significantly greater reductions in cMetS score after 1 year. CONCLUSIONS The findings from the current study suggest that individuals with certain genotypes may benefit more from a lifestyle intervention for MetS and that specific variants, either independently or as part of a GRS, could be used as a nutrigenomic tool to tailor the intervention to reduce the risk of MetS.
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Serum adiponectin and protein-energy wasting in predialysis chronic kidney disease.
Hyun, YY, Lee, KB, Oh, KH, Ahn, C, Park, SK, Chae, DW, Yoo, TH, Cho, KH, Kim, YS, Hwang, YH, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2017;:254-260
Abstract
OBJECTIVE Adiponectin (ADPN) has antiatherogenic, anti-inflammatory, and insulin-sensitizing effects. Serum ADPN levels are increased in patients with chronic kidney diseases (CKD), and higher ADPN is paradoxically a predictor of mortality in these patients. The aim of this study was to determine the association between serum ADPN levels and protein-energy wasting (PEW) in predialysis CKD. METHOD We examined serum ADPN concentrations and PEW in 1303 patients from the KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease) study. PEW was defined as the presence of three or more of the following four indicators: serum albumin <3.8 g/dL, body mass index <23 kg/m2, urine creatinine excretion (UCE) below the lower quartile, and daily dietary protein intake <0.6 g/kg. We analyzed the association between PEW and ADPN using a multivariate regression model after adjustment for socioeconomic factors, comorbidities, and laboratory findings. RESULTS Among 1303 predialysis CKD patients, 72 (5.5%) had PEW. In multivariate logistic regression analysis, higher ADPN level was associated with PEW (odds ratio, 1.04; 95% confidence interval [CI], 1.01-1.08 by 1 μg/mL ADPN). The highest ADPN quartile was associated with PEW in comparison with the lowest quartile (odds ratio, 10.54; 95% CI, 1.28-86.74). In multiple linear regression with PEW indicators, ADPN was more strongly associated with UCE (β = -2.21; 95% CI, -4.13 to -0.28; R2 = 0.67). CONCLUSION High ADPN is independently associated with PEW. Among PEW indicators, serum ADPN is closely associated with UCE as an indirect measure of muscle mass.
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T-cadherin gene variants are associated with nephropathy in subjects with type 1 diabetes.
Nicolas, A, Mohammedi, K, Bastard, JP, Fellahi, S, Bellili-Muñoz, N, Roussel, R, Hadjadj, S, Marre, M, Velho, G, Fumeron, F
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(12):1987-1993
Abstract
BACKGROUND High plasma adiponectin levels are associated with diabetic nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be associated with adiponectin levels. We investigated associations between allelic variations of CDH13 and DN in subjects with type 1 diabetes. METHODS Two CDH13 polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up), 'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and 'Génétique de la Néphropathie Diabétique' (GENEDIAB) (n = 456, 9-year follow-up for n = 283) cohorts. Adiponectin levels were measured in plasma samples from GENESIS and GENEDIAB cohorts. RESULTS Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor allele of rs3865188 was associated with lower adiponectin levels (P = 0.006). rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P = 0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with baseline prevalence of established/advanced DN. These polymorphisms were also associated with the risk of ESRD (0.006 < P < 0.03). The association between rs11646213 (but not rs3865188) and renal function remained significant after adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR) 1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P = 0.04) were associated with risk of renal events (defined as progression to more severe DN stages). CONCLUSIONS Plasma adiponectin levels are associated with the prevalence of DN and the incidence of ESRD in patients with type 1 diabetes. CDH13 polymorphisms are also associated with the prevalence and incidence of DN, and with the incidence of ESRD in these patients. The association between CDH13 and DN may be due to pleiotropic effects, both dependent and independent of plasma adiponectin levels.
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Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program.
Goldberg, RB, Temprosa, M, Mele, L, Orchard, T, Mather, K, Bray, G, Horton, E, Kitabchi, A, Krakoff, J, Marcovina, S, et al
Metabolism: clinical and experimental. 2016;(5):764-775
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OBJECTIVE In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP. METHODS The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis. RESULTS After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect. CONCLUSION While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.
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Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes.
Kim, C, Christophi, CA, Goldberg, RB, Perreault, L, Dabelea, D, Marcovina, SM, Pi-Sunyer, X, Barrett-Connor, E
Diabetic medicine : a journal of the British Diabetic Association. 2016;(1):32-8
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AIM: To examine concentrations of biomarkers (adiponectin, C-reactive protein, fibrinogen and tissue plasminogen-activator antigen) associated with glucose homeostasis and diabetes risk by history of gestational diabetes (GDM). METHODS We conducted a secondary analysis of the Diabetes Prevention Program, a randomized trial of lifestyle intervention or metformin for diabetes prevention. At baseline, participants were overweight and had impaired glucose tolerance. Biomarkers at baseline and 1 year after enrolment were compared between parous women with (n = 350) and without histories of GDM (n = 1466). Cox proportional hazard models evaluated whether history of GDM was associated with diabetes risk, after adjustment for baseline biomarker levels as well as for change in biomarker levels, demographic factors and anthropometrics. RESULTS At baseline, women with histories of GDM had lower adiponectin (7.5 μg/ml vs. 8.7 μg/ml; p < 0.0001) and greater log C-reactive protein (-0.90 mg/l vs. -0.78 mg/l, p = 0.04) levels than women without histories of GDM, but these associations did not persist after adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator antigen were similar between women with and without histories of GDM. Women with and without histories of GDM had a similar pattern of changes in biomarkers within randomization arm. Adjustment for age, race/ethnicity, baseline weight, change in weight, baseline biomarker level and change in biomarker level did not significantly alter the association between history of GDM, and diabetes risk. CONCLUSIONS Among women with impaired glucose tolerance, biomarkers in women with and without histories of GDM are similar and respond similarly to lifestyle changes and metformin. Adjustment for biomarker levels did not explain the higher risk of diabetes observed in women with histories of GDM.
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Effects of Oral L-Carnitine Supplementation on Leptin and Adiponectin Levels and Body Weight of Hemodialysis Patients: a Randomized Clinical Trial.
Ahmadi, S, Dehghan Banadaki, S, Mozaffari-Khosravi, H
Iranian journal of kidney diseases. 2016;(3):144-50
Abstract
INTRODUCTION Carnitine supplementation may improve the general health and quality of life of hemodialysis patients by improving adipokines levels. The aim of the study was to investigate the effects of L-carnitine supplementation on leptin levels, adiponectin levels, and body weight of hemodialysis patients. MATERIALS AND METHODS Fifty hemodialysis patients were randomly divided into the carnitine group, who received oral L-carnitine, 1 g/L for 3 months, and the control group. Anthropometric measurements and serum levels of adipokines were measured at baseline and at the end of the intervention. RESULTS Forty-two participants completed the study. Serum leptin concentrations decreased after 12 weeks of the intervention in both groups, but these changes were not significant. The mean change of leptin concentration were, -1.7 ± 19.0 µg/mL and -7.1 ± 20.0 µg/mL in the carnitine group and the control group, respectively (P = .39). The mean adiponectin levels at baseline and after the intervention were 8.6 ± 11.19 µg/mL and 9.8 ± 4.1 µg/mL in the carnitine group (P = .67) and 5.0 ± 2.5 µg/mL and 11.2 ± 5.4 µg/mL in the control group, respectively (P < .001). Serum adiponectin levels increased significantly in the control group only. The decrease in body mass index was not significant. CONCLUSIONS This study showed that a daily supplementation of 1000 mg oral syrup of L-carnitine for 12 weeks did not affect leptin and adiponectin levels or the body weight or body mass index of hemodialysis patients.
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In prostate cancer, low adiponectin levels are not associated with insulin resistance.
Michalakis, K, Venihaki, M, Mantzoros, C, Vazaiou, A, Ilias, I, Gryparis, A, Margioris, AN
European journal of clinical investigation. 2015;(6):572-8
Abstract
PURPOSE Adiponectin, an adipose tissue-derived hormone with insulin-sensitizing effect, has been inversely associated with several hormonally dependent malignancies. Prostate cancer is associated with low levels of adiponectin, which have been proposed as an independent risk factor for this malignancy. Aim of this study was to examine whether hypoadiponectinaemia in prostate is associated with insulin resistance. EXPERIMENTAL DESIGN Plasma samples and covariate data in the context of a case-control study of 300 Greek men were evaluated including 75 patients with prostate cancer, 75 patients with benign prostatic hyperplasia (BPH) and 150 age-matched healthy controls. RESULTS Patients with prostate cancer had significantly lower plasma adiponectin levels compared with the other two groups, that is BPH patients and healthy controls (7.4 ± 5 ng/mL vs. 11.5 ± 6.4 ng/mL and 12.8 ± 8 ng/mL, respectively). On the other hand, no statistically significant differences were found between patients with prostate cancer and the other two groups for both HOMA-IR and QUICKI (P-value = 0.551). As expected, in all three groups, the levels of adiponectin correlated negatively with HOMA-IR (rho = -0.214, P-value = 0.006), QUICKI (rho = 0.214, P-value = 0.006) and insulin levels (rho = 0.942, P-value < 0.001). CONCLUSION In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.
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Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights From Look AHEAD.
Belalcazar, LM, Lang, W, Haffner, SM, Schwenke, DC, Kriska, A, Balasubramanyam, A, Hoogeveen, RC, Pi-Sunyer, FX, Tracy, RP, Ballantyne, CM, et al
Diabetes care. 2015;(8):1544-50
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OBJECTIVE This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes. RESEARCH DESIGN AND METHODS Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense. Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins. RESULTS ILI resulted in greater improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P < 0.0001). Weight loss and improved fitness were each associated with changes in adiponectins in men and women (P < 0.001 for all), after adjusting for baseline adiponectins, demographics, clinical variables, and treatment arm. Weight loss contributed an additional 4-5% to the variance of change in adiponectins than did increased fitness in men; in women, the contributions of improved fitness (1% greater) and of weight loss were similar. When weight and fitness changes were both accounted for, weight loss in men and increased fitness in women retained their strong associations (P < 0.0001) with adiponectin change. CONCLUSIONS Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes. Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations.