Serum Adiponectin Is Increased in Type 1 Diabetic Patients With Nephropathy

Abstract

OBJECTIVE -To elucidate whether serum adiponectin is associated with renal function, low-grade inflammatory markers, metabolic control, and insulin resistance in type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS-A total of 189 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based on their urinary albumin excretion rate (AER): patients with normal AER (n ϭ 66) had no antihypertensive medication, while patients with microalbuminuria (n ϭ 63) or macroalbuminuria (n ϭ 60) were all treated with an ACE inhibitor. Renal function was estimated with the Cockcroft-Gault formula. Adiponectin was measured by an in-house time-resolved immunofluorometric assay.RESULTS -Adiponectin concentrations were higher in women than in men, but since there was no significant difference in sex distribution between the groups, data were pooled. Adiponectin concentrations were higher in patients with macroalbuminuria (19.8 Ϯ 12.0 mg/l) than in patients with microalbuminuria (13.1 Ϯ 4.8 mg/l) or normoalbuminuria (11.8 Ϯ 4.2 mg/l). In a univariate analysis, adiponectin was positively associated with creatinine (r ϭ 0.41; P Ͻ 0.0001), AER (r ϭ 0.33; P Ͻ 0.0001), interleukin-6 (r ϭ 0.22; P ϭ 0.002), systolic blood pressure (r ϭ 0.22; P ϭ 0.004), HbA 1c (r ϭ 0.17; P ϭ 0.02), total cholesterol (r ϭ 0.16; P ϭ 0.03), and HDL cholesterol (r ϭ 0.16; P ϭ 0.03) and negatively with estimated glomerular filtration rate (GFR; r ϭ Ϫ0.52; P Ͻ 0.0001) and waist-to-hip ratio (WHR; r ϭ Ϫ0.16; P ϭ 0.03). In a multiple linear regression analysis including the above variables, estimated GFR, AER, and WHR were independently associated with adiponectin levels (r 2 ϭ 0.32).CONCLUSIONS -Serum adiponectin concentrations are increased in type 1 diabetic patients with nephropathy, and levels are further associated with renal insufficiency. Diabetes Care 28:1410 -1414, 2005D iabetic nephropathy is associated with insulin resistance and low-grade inflammation in type 1 diabetes (1,2). Circulatory levels of adiponectin, a hormone that is secreted exclusively from the adipocytes (3), correlate negatively with insulin resistance (4 -6), serum triglycerides, fasting serum insulin, and fasting plasma glucose concentrations (5-7). Low plasma adiponectin concentrations are found in obesity (8,9), type 2 diabetes (7,8), and in patients with coronary artery disease (7,10). Women have higher adiponectin concentrations than men (6,7), a difference that may be explained by the effect of testosterone (11). Weight reduction increases adiponectin in both diabetic and nondiabetic subjects (7). Interestingly, the thiazolidinediones (peroxisome proliferatoractivated receptor ␥ agonists) have emerged as an effective treatment for insulin-resistant states (12), and one of the mechanisms may be their ability to stimulate adiponectin synthesis (13,14).The fact that adiponectin may have an anti-inflammatory effect is supported by the reciprocal association between adiponectin and C-reactive protein (CRP) in pat...

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

“…Previous cross-sectional studies in adults with type 1 diabetes have shown a variable relationship between adiponectin levels and glycaemic control, with a negative [1], a positive [11] or no correlation at all [13]. In these studies, differences between the sexes were either not found or not reported.…”

“…However, testing for interaction with sex supported these discordant observations. In addition, higher adiponectin levels in adults have been found in association with reduced glomerular filtration rate, suggesting reduced clearance of adiponectin [11,12].…”

“…In adults with type 1 diabetes, higher adiponectin levels have been observed compared with controls [10], which, paradoxically, may be associated with microalbuminuria [11,12], reduced glomerular filtration rate [11,12], overt nephropathy and retinopathy [13]. Such observations conflict with data showing associations between insulin resistance and risk of microvascular complications in type 1 diabetes [14].…”

Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

“…Plasma adiponectin was determined by an in-house timeresolved immunofluorometric assay (TR-IFMA) based on commercial antibodies and recombinant human adiponectin (R&D Systems, Abingdon, UK) as recently described [33]. Adiponectin has a molecular mass of ∼30-36 kDa depending on the degree of glycosylation, but the molecule is known to form a wide range of polymers in vivo.…”

Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes

“…However, an increase in circulating adiponectin is found in patients with kidney diseases [11][12][13]. Polymorphisms in the two small regions of ADIPOQ, one in the promoter and another in the boundary of exon 2-intron 2, are the most commonly discussed variants.…”