Why does diabetic autonomic neuropathy predict IDDM mortality? An analysis from the Pittsburgh Epidemiology of Diabetes Complications Study.

BACKGROUND: Previous studies have suggested that IDDM subjects with diabetic autonomic neuropathy (DAN) have a greatly increased risk of mortality which may relate to a specific cardiologic etiology.
OBJECTIVES: To examine the predictors of DAN in IDDM and its relationship to subsequent mortality. STUDY POPULATION: The Epidemiology of Diabetes Complications Study based on an incident cohort of childhood onset IDDM subjects. Data from two examinations, separated by 2 years, are utilized.
METHODS: Diabetic autonomic neuropathy was determined by Expiration/Inspiration (E/I ratio). A variety of baseline risk factors were related to its subsequent incidence (n = 57 out of 325 subjects free of DAN at baseline). Two-year mortality by DAN status was also determined for all 479 subjects seen at baseline.
RESULTS: Duration of diabetes, the cardiovascular risk profile (hypertension, elevated LDL cholesterol and triglycerides), and other complications (e.g. nephropathy) were all univariately associated with subsequent DAN (P < 0.01). Smoking status and hemoglobin A1 (HbA1) but less strongly, related (P < 0.05). Cox proportional hazards modeling showed diabetes duration and HbA1 to be significant independent predictors. Distal Symmetrical Polyneuropathy also contributed if added to the model. Mortality was increased four-fold in those with DAN (P = 0.005), although this difference no longer was significant after adjustment for baseline nephropathy (P = 0.35) or hypertension (P = 0.42).
CONCLUSIONS: Duration of diabetes and HbA1 are the major predictors of DAN. However, although DAN is clearly associated with increased mortality, this is largely explained by associations with complications (e.g. nephropathy) and increased cardiovascular risk factors (e.g. hypertension).