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

Department of Internal Medicine, Takasago Municipal Hospital, Takasago, Japan.
American Journal of Nephrology (Impact Factor: 2.67). 02/2006; 26(5):476-82. DOI: 10.1159/000096870
Source: PubMed


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.

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    • "I.1 and I.2; Table 4). Adiponectin was significantly elevated in patients with macroalbuminuria (n = 64) relative to patients with microalbuminuria (n = 92) [SMD = 0.87; 95%CI = 0.23, 1.51; p = 0.007; I 2 = 67%] from four studies (Kato et al., 2008; Komaba et al., 2006; Koshimura et al., 2004; Ran et al., 2010) confirmed in a sensitivity analysis (Supplementary Figs. J.1 and J.2; Table 4 "

    Full-text · Dataset · Dec 2015
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    • "I.1 and I.2; Table 4). Adiponectin was significantly elevated in patients with macroalbuminuria (n = 64) relative to patients with microalbuminuria (n = 92) [SMD = 0.87; 95%CI = 0.23, 1.51; p = 0.007; I 2 = 67%] from four studies (Kato et al., 2008; Komaba et al., 2006; Koshimura et al., 2004; Ran et al., 2010) confirmed in a sensitivity analysis (Supplementary Figs. J.1 and J.2; Table 4 "
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    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 · Journal of Diabetes and its Complications
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    • "In these studies, the type 2 diabetics with proteinuria had increased insulin resistance compared with the diabetics without proteinuria and this may account for the reported downregulation of serum adiponectin levels in patients with type 2 diabetes and proteinuria. Regarding the role of adiponectin subfractions in renal physiology, circulating HMW adiponectin appears to be elevated in patients with macroalbuminuria and microalbuminuria and the serum HMW adiponectin–UAE association has been reported to be positive (Komaba et al. 2006). Taking into account the relatively low permeability of the glomerular filtration barrier for HMW adiponectin compared with the other subforms of adiponectin, serum HMW adiponectin levels are expected to best reflect the production of adiponectin by adipose tissue. "
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    ABSTRACT: Adiponectin is secreted by the adipose tissue and is downregulated in states of obesity and insulin resistance. There is a growing body of evidence indicating that adiponectin has renoprotective effects and protects against the development of albuminuria in rodent experiments. Adiponectin crossing the glomerular filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress in kidneys through activation of AMP-activated protein kinase. Moreover, microalbuminuria is a well established early sign of progressive cardiovascular and renal disease even in subjects with preserved glomerular filtration rate. Studies investigating the relationship between serum adiponectin levels and urinary albumin excretion rate (UAE) have yielded conflicting data and the mechanisms underlying the interplay between adiponectin and albuminuria remain to be elucidaded. This article constitutes a critical review attempting to clarify any resting confusion on this matter. Furthermore, this article presents the clinical significance of adiponectin-albuminuria interplay, suggesting that adiponectin is possibly involved in the development of albuminuria that is associated with obesity, diabetes and cardiovascular disease and may mediate at least in part the actions of medical treatments that influence UAE, such as angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, thiazolidinediones, fenofibrate and diet. Further studies to investigate more thoroughly the renoprotective role of adiponectin in the human setting should be carefully planned, focusing on causality and the possible impact of adiponectin on the development of albuminuria in specific clinical settings.
    Full-text · Article · Jan 2014 · Journal of Endocrinology
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