Diabetic retinopathy is associated with elevated serum asymmetric and symmetric dimethylarginines

Abstract

Objective: Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and l-arginine directly influence nitric oxide production. Our objective was to test whether serum ADMA, SDMA, or l-arginine levels correlate with diabetic retinopathy subtype or severity.

Research design and methods: A total of 162 subjects with type 1 diabetes and 343 with type 2 diabetes, of whom 329 subjects had no diabetic retinopathy, 27 had nonproliferative diabetic retinopathy (NPDR), 101 had proliferative diabetic retinopathy (PDR), and 107 had clinically significant macular edema (CSME), were recruited. Blinding diabetic retinopathy was defined as severe NPDR, PDR, or CSME. Serum ADMA, SDMA, and l-arginine concentrations were determined by mass spectroscopy.

Results: In multivariate analysis, blinding diabetic retinopathy, PDR, and nephropathy were associated with significantly increased serum levels of ADMA (P < 0.001), SDMA (P < 0.001), and l-arginine (P = 0.001). Elevated ADMA (P < 0.001) and SDMA (P < 0.001) were also significantly associated with CSME.

Conclusions: Severe forms of diabetic retinopathy are associated with elevated serum ADMA, SDMA, and l-arginine. Further investigation is required to determine whether these findings are of clinical relevance.

Figure 1

Box plots of untransformed concentrations of l-arginine, ADMA, and SDMA (μmol/l) in all subjects without diabetic retinopathy (DR) (n = 330) and blinding diabetic retinopathy (n = 175) are shown, regardless of type of diabetes. Data are shown as the 25th, 50th, and 75th percentiles (represented by gray boxes), range (shown as whiskers; outliers have been removed), and the median (white horizontal line). Means ± SD and adjusted P values for each analyte are provided under the corresponding box plot. P values have been adjusted for type of diabetes, diabetes duration, age, hypertension, hypercholesterolemia, and nephropathy.