Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function.
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.
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ABSTRACT: Le tissu adipeux a longtemps été considéré comme un simple organe de réserve énergétique. Il est désormais parfaitement établi qu’il est aussi capable de produire de nombreuses molécules appelées adipokines, parmi lesquelles l’adiponectine occupe une place privilégiée. Cette hormone est synthétisée et sécrétée de façon très abondante par l’adipocyte. Elle possède des propriétés originales insulino-sensibilisatrices, anti-inflammatoires et anti-mitogènes. Cependant, elle ne semble pas toujours associée à un état clinique favorable, ce qui est illustré dans les pathologies rénales où des niveaux plasmatiques élevés de l’hormone ont une valeur prédictive péjorative. Ceci est aussi le cas dans les formes sévères de résistance à l’insuline par dysfonctionnement du récepteur de l’insuline, où les patients présentent des concentrations circulantes élevées d’adiponectine alors que les formes communes d’insulinorésistance sont associées à une adiponectinémie basse. Des investigations poussées demeurent nécessaires afin de préciser la pertinence physiologique et thérapeutique de l’adiponectine.Obésité 7(4).
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ABSTRACT: Recently, several reports addressed the associations of adiponectin (ADIPOQ) gene polymorphisms with abnormal adiponectin serum levels, type 2 diabetes mellitus (T2DM), and diabetic nephropathy (DN); however, results are inconsistent. This study aimed to investigate the possible association of ADIPOQ gene polymorphisms with T2DM and/or DN and whether they affect serum adiponectin levels in Egyptian population. Two hundred and ninety-six T2DM patients (100 normoalbuminuric patients, 103 microalbuminuric patients, and 93 macroalbuminuric patients) and 209 controls were enrolled in the present study. Polymorphisms of +45, -11391, and +276 of the ADIPOQ gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum adiponectin was measured using ELISA. Our results revealed that ADIPOQ +45 TG and GG genotypes and G allele were significantly associated with T2DM, micro/macroalbuminuria, and decreased serum adiponectin level. ADIPOQ -11391 AA genotype frequency was significantly increased in T2DM group. Moreover, GA and AA genotypes and A allele of ADIPOQ -11391 were significantly associated with susceptibility to macroalbuminuria despite increased serum adiponectin concentrations. While, ADIPOQ +276 TT genotype and T allele were protective factors regarding the susceptibility to T2DM and micro/macroalbuminuria, and they were significantly associated with increased adiponectin levels. We observed also that the decrease of the serum Adiponectin level was accompanied by an insulin resistance, albuminuria, as well as an increase of serum creatinine. We concluded that ADIPOQ +45; ADIPOQ -11391 gene polymorphisms are associated with T2DM and/or DN in Egyptian population. While, ADIPOQ +276 gene polymorphism is a protective factor regarding T2DM and/or DN susceptibility.Molecular Biology Reports 01/2014; · 1.96 Impact Factor
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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.Journal of Endocrinology 01/2014; · 3.59 Impact Factor