An explanation for the increase in heart disease mortality rates in diabetic Pima Indians: effect of renal replacement therapy

OBJECTIVE: Diabetic nephropathy (DN) became the leading cause of death in diabetic Pima Indians in the 1970s, but was superseded by ischemic heart disease (IHD) in the 1980s. This study tests the hypothesis that the rise in the IHD death rate between 1965 and 1998 is attributable to access to renal replacement therapy (RRT). RESEARCH DESIGN AND METHODS: Underlying causes of death were determined among 2,095 diabetic Pima Indians > or = 35 years old during four 8.5-year time intervals. To assess the effect of access to RRT on IHD death rates, trends were reexamined after subjects receiving RRT were classified as if they had died of DN. RESULTS: During a median follow-up of 11.1 years (range 0.01-34), 818 subjects died. The age- and sex-adjusted DN death rate decreased over the 34-year study (P = 0.05), whereas the IHD death rate increased from 3.3 deaths/1,000 person-years (95% CI 1.4-5.2) to 6.3 deaths/1,000 person-years (95% CI 4.5-8.0; P = 0.03). After 151 subjects on RRT were reclassified as if they had died of DN, the death rate for DN increased from 4.8 deaths/1,000 person-years (95% CI 2.6-7) to 11.3 deaths/1,000 person-years (95% CI 9-13.6; P = 0.0007), whereas the increase in the IHD death rate disappeared (P = 0.57). CONCLUSIONS: The incidence rate of renal failure attributable to diabetes has increased rapidly over the past 34 years in Pima Indians. IHD has emerged as the leading cause of death due largely to the availability of RRT and to changes in the pattern of death among those with DN.