Increased Serum High-Molecular-Weight Complex of Adiponectin in Type 2 Diabetic Patients with Impaired Renal Function

ArticleinAmerican Journal of Nephrology 26(5):476-82 · February 2006with4 Reads
DOI: 10.1159/000096870 · Source: PubMed
Abstract
Adiponectin, an adipocyte-derived protein, has been shown to exert antidiabetic, anti-inflammatory, and antiatherosclerotic effects. Although recent reports show an increase in the total adiponectin levels in chronic kidney disease patients and in patients with end-stage renal disease, the nature of biodegradation and renal involvement of adiponectin is largely unknown. We aimed at determining whether the high-molecular-weight (HMW) complex of adiponectin is associated with renal insufficiency in type 2 diabetic patients. A total of 179 type 2 diabetic patients were selected from among outpatients and divided into four groups according to their albumin-to-creatinine ratio: patients with normoalbuminuria (n = 86), patients with microalbuminuria (n = 44), patients with macroalbuminuria (n = 23), and patients on hemodialysis (n = 26). The serum HMW adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. The HMW adiponectin levels were higher in patients on hemodialysis (17.1 +/- 8.2 microg/ml) and in those with macroalbuminuria (14.3 +/- 8.7 microg/ml) than in patients with normoalbuminuria (7.2 +/- 5.6 microg/ml) and microalbuminuria (10.8 +/- 7.0 microg/ml). Univariate linear regression analysis showed that the HMW adiponectin concentrations correlated negatively with the estimated glomerular filtration rate in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria (r = -0.42, p < 0.001). Multiple stepwise regression analysis disclosed that estimated glomerular filtration rate, pioglitazone therapy, gender differences, and systolic blood pressure were independently associated with HMW adiponectin levels (r = 0.56). The serum HMW adiponectin concentrations are higher in type 2 diabetic patients with nephropathy, and these levels are also associated with renal insufficiency.
    • "Despite this literature, there has been little direct examination of the role of leptin and adiponectin in microvascular complications. We identified several studies that suggest leptin and adiponectin are relevant to these conditions (Asakawa et al., 2001; Cha et al., 2012; Chan et al., 2004; Choe et al., 2013; Chung et al., 2005; Dossarps et al., 2014; Fruehwald-Schultes et al., 1999; Fujita et al., 2006; Hanai et al., 2010; Jung et al., 2012 Jung et al., , 2014 Kato et al., 2008; Komaba et al., 2006; Kopeisy et al., 2011; Koshimura et al., 2004; Matsuda, Kawasaki, Inoue, et al., 2004; Matsuda, Kawasaki, Yamada, et al., 2004; Parveen & Zia Qureshi, 2013; Pradeepa et al., 2015, Ran et al., 2010, Saito et al., 2007 Sari et al., 2010; Swellam et al., 2009; Uckaya et al., 2000; Wilson et al., 1998; Yilmaz et al., 2004 Yilmaz et al., , 2008). As this investigation attests, these studies have proven to be heterogeneous in their findings of associations between leptin and adiponectin and diabetic microvascular complications. "
    Full-text · Dataset · Dec 2015 · PLoS ONE
    • "Despite this literature, there has been little direct examination of the role of leptin and adiponectin in microvascular complications. We identified several studies that suggest leptin and adiponectin are relevant to these conditions (Asakawa et al., 2001; Cha et al., 2012; Chan et al., 2004; Choe et al., 2013; Chung et al., 2005; Dossarps et al., 2014; Fruehwald-Schultes et al., 1999; Fujita et al., 2006; Hanai et al., 2010; Jung et al., 2012 Jung et al., , 2014 Kato et al., 2008; Komaba et al., 2006; Kopeisy et al., 2011; Koshimura et al., 2004; Matsuda, Kawasaki, Inoue, et al., 2004; Matsuda, Kawasaki, Yamada, et al., 2004; Parveen & Zia Qureshi, 2013; Pradeepa et al., 2015, Ran et al., 2010, Saito et al., 2007 Sari et al., 2010; Swellam et al., 2009; Uckaya et al., 2000; Wilson et al., 1998; Yilmaz et al., 2004 Yilmaz et al., , 2008). As this investigation attests, these studies have proven to be heterogeneous in their findings of associations between leptin and adiponectin and diabetic microvascular complications. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. Methods: This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic. Results: Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p<0.001), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p<0.00001), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p<0.00001), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p<0.00001). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size. Discussion: Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings.
    Full-text · Article · Nov 2015
    • "Elevated leptin levels have also been consistently shown to be associated with CKD in the general population as well as among diabetic and obese non-diabetic patients [11,1920212223. However, in contrast to the finding of an association between lower adiponectin levels and risk factors of CKD, higher adiponectin levels were found in end-stage renal disease (ESRD) patients requiring dialysis [24,25]. The role of adiponectin in non-dialysis dependent CKD is also inconsistent [13,21,22,2627282930, with some studies showing lower levels of adiponectin to be associated with CKD, while others showing higher levels to be associated with CKD or no significant association. "
    [Show abstract] [Hide abstract] ABSTRACT: Adiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults. We conducted a case-control study (450 CKD cases and 920 controls matched for age, sex and ethnicity) involving Chinese and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007-2011). CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 from serum creatinine. Serum adiponectin and leptin levels were measured using commercially available ELISA. Odds ratio of CKD associated with elevated adiponectin and leptin levels were estimated using logistic regression models adjusted for age, gender, ethnicity, education, smoking, body mass index, diabetes, blood pressure, total and HDL cholesterol. CKD cases had higher levels of leptin (mean [SD] 9.7 [11.5] vs.16.9 [20.2] ng/mL, p<0.0001) and adiponectin (10.4 [7.4] vs. 9.2 [4.2], p = 0.001) compared to controls. In multi-variable models, compared to those in the lowest quartile, the OR (95% confidence interval) of CKD among those in the highest quartile were: 6.46 (3.84, 10.88), 1.94 (1.32-2.85) and 2.88 (1.78-4.64) for leptin, adiponectin and LAR. Similar associations were also observed when adiponectin and leptin were analyzed as continuous variables. This positive association of serum adiponectin, leptin and LAR with CKD was consistently present in subgroups of gender, ethnicity, diabetes, hypertension and overweight status (all P-interaction >0.1). Higher levels of serum adiponectin, leptin and LAR were positively associated with CKD independent of traditional risk factors in this Asian population.
    Full-text · Article · Mar 2015
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