Plasma Asymmetric Dimethylarginine (ADMA) Is Associated With Retinopathy in Type 2 Diabetes
- Maciej T. Malecki, MD, PHD1,
- Anetta Undas, MD, PHD2,
- Katarzyna Cyganek, MD, PHD1,
- Barbara Mirkiewicz-Sieradzka, MD, PHD1,
- Pawel Wolkow, MD, PHD3,
- Grzegorz Osmenda, MD, PHD3,
- Malgorzata Walus-Miarka, MD1,
- Tomasz J. Guzik, MD, PHD3 and
- Jacek Sieradzki, MD, PHD1
- 1Department of Metabolic Diseases, Jagiellonian University, Krakow, Poland
- 2Institute of Cardiology, Jagiellonian University, Krakow, Poland
- 3Department of Pharmacology, Jagiellonian University, Krakow, Poland
- Address correspondence and reprint requests to Maciej T. Malecki, MD, PhD, Metabolic Diseases, Jagiellonian University, 15 Kopernika St., 31-501 Krakow, Poland. E-mail: malecki_malecki{at}yahoo.com
Decreased availability of nitric oxide (NO), which contributes to the development of diabetes vascular complications (1), is partially related to asymmetric dimethylarginine (ADMA). ADMA is an endogenous NO synthase inhibitor (2) and a competitive inhibitor of cellular l-arginine uptake (3). ADMA has been associated with atherosclerosis in nondiabetic populations (4) and with diabetic nephropathy in type 1 diabetes (5). In humans, the stereoisomer of ADMA, symmetric dimethylarginine (SDMA), is produced in equivalent quantities; though it does affect NO synthesis, SDMA may compete with arginine for cellular uptake (6). Our objective was to evaluate the relationship between plasma ADMA and diabetic retinopathy in type 2 diabetes.
RESEARCH DESIGN AND METHODS
We examined 182 consecutive type 2 diabetic patients (mean age at examination 56.2 ± 6.5 years). Previously described inclusion criteria were used (7). Biochemical measurements were done using standard methods. Creatinine clearance was calculated according to the Cockroft-Gault formula. The control group consisted of 52 apparently healthy individuals matched for age and sex (mean age 54.5 ± 7.1 years). This study was approved by the local ethics committee.
All type 2 diabetic patients underwent ophthalmological evaluation. Color fundus photographs were taken as previously described (8). The final diabetic retinopathy diagnosis was based on both ophthalmoscopy and photography (Protocol of Ophthalmological Examination can be found in an online appendix (available at dx.doi.org/10.2337/dc07-1138) (9). The patients were assigned to one of three groups: 1) no diabetic retinopathy, 2) nonproliferative diabetic retinopathy, or 3) proliferative diabetic retinopathy.
Plasma ADMA, SDMA, and l-arginine levels were measured …
