N Engl J Med 2005; 352: 341-350 Solomon Tesfaye， M.D.， Nish Chaturvedi， M.D.， Simon E.M. Eaton， D.M.， John D. Ward， M.D.， Christos Manes， M.D.， Constantin Ionescu-Tirgoviste， M.D.， Daniel R. Witte， Ph.D.， John H. Fuller， M.A.， for the EURODIAB Prospective Complications Study Group

Background Other than glycemic control， there are no treatments for diabetic neuropathy. Thus， identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study.

Methods Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999)， with a mean (±SD) follow-up of 7.3±0.6 years. A standardized protocol included clinical evaluation， quantitative sensory testing， and autonomic-function tests. Serum lipids and lipoproteins， glycosylated hemoglobin， and the urinary albumin excretion rate were measured in a central laboratory.

Results At follow-up， neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors， we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides， a higher body-mass index， higher von Willebrand factor levels and urinary albumin excretion rate， hypertension， and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications， we found that duration of diabetes， current glycosylated hemoglobin value， change in glycosylated hemoglobin value during the follow-up period， body-mass index， and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy， independent of cardiovascular risk factors.

Conclusions This prospective study indicates that， apart from glycemic control， the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors， including a raised triglyceride level， body-mass index， smoking， and hypertension.