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Synergistic Association of Metabolic Syndrome and Overt Nephropathy With Elevated Asymmetric Dimethylarginine in Serum and Impaired Cutaneous Microvasodilation in Patients With Type 2 Diabetes

Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Saitama, Japan

Address correspondence and reprint requests to Yoshimasa Aso, MD, Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. E-mail: yaso@dokkyomed.ac.jp

Abbreviations: ADMA, asymmetric dimethylarginine • CKD, chronic kidney disease

The first 20% of the full text of this article appears below.

	INTRODUCTION

 
Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease as well as end-stage renal disease (1). Diabetic nephropathy is an important cause and exacerbating factor in CKD. Recent studies have demonstrated a close relationship between prevalence of the metabolic syndrome and CKD (2,3). Microvascular endothelial dysfunction resulting from impaired nitric oxide biosynthesis and bioavailability is associated with occurrence of metabolic syndrome and type 2 diabetes (4,5). de Jongh et al. (6) found cutaneous microvascular function to be related to degree of insulin resistance in obese women, suggesting that microvascular endothelial dysfunction in the skin can predict metabolic syndrome–related microangiopathy and insulin resistance. Thus, microvascular endothelial dysfunction may be a causal factor linking metabolic syndrome and CKD.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, causes vasoconstriction and limits blood flow, resulting in elevated blood pressure in humans (7,8). Elevated plasma ADMA concentrations are found in patients with renal insufficiency (9), diabetes (10), and metabolic syndrome (11). Accordingly, increased plasma ADMA may contribute to microvascular endothelial dysfunction observed in individuals with metabolic syndrome or with CKD.

We examined cutaneous microvascular responses to heat applied locally to the skin of the dorsum of the foot in type 2 diabetic patients with or without metabolic syndrome or overt nephropathy, measuring cutaneous blood flow by laser Doppler flowmetry as well as serum ADMA concentration.

	RESEARCH DESIGN AND METHODS

 
We studied 105 type 2 diabetic patients (41 female and 64 . . . [Full Text of this Article]

Skin blood flow measurements

	RESULTS

 

	CONCLUSIONS

 

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