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Effect of Youth-Onset Type 2 Diabetes Mellitus on Incidence of End-Stage Renal Disease and Mortality in Young and Middle-Aged Pima Indians
Meda E. Pavkov, MD, PhD;
Peter H. Bennett, MB, FRCP;
William C. Knowler, MD, DrPH;
Jonathan Krakoff, MD;
Maurice L. Sievers, MD;
Robert G. Nelson, MD, PhD
JAMA. 2006;296:421-426.
Context The long-term outcome of persons with youth-onset type 2 diabetes mellitus has not been well described.
Objective To compare incidence of diabetic end-stage renal disease (ESRD) and mortality in Pima Indians with youth- and older-onset type 2 diabetes mellitus.
Design, Setting, and Participants Longitudinal population-based study conducted between 1965 and 2002 in Pima Indians from the state of Arizona. Participants were divided into 2 groups: (1) youth-onset type 2 diabetes mellitus (onset <20 years of age) and (2) older-onset type 2 diabetes mellitus (onset  20 - <55 years of age). Events and person-years of follow-up were stratified in a time-dependent fashion by decades of age. End-stage renal disease was defined as dialysis attributed to diabetic nephropathy or death from diabetic nephropathy.
Main Outcome Measures Incidence rate of diabetic ESRD and mortality between 25 and 55 years of age, according to age at onset of type 2 diabetes mellitus.
Results Among the 1856 diabetic participants, 96 had youth-onset type 2 diabetes mellitus. The age-sex–adjusted incidence of diabetic ESRD was 25.0 cases per 1000 person-years (95% confidence interval [CI], 6.7-43.1) in youth-onset diabetes mellitus and 5.4 cases per 1000 person-years (95% CI, 4.4-6.4) in older-onset diabetes mellitus (incidence rate ratio, 4.6; 95% CI, 2.2-9.8). Age-specific incidence rates were higher in participants with youth-onset diabetes mellitus at all ages. Between 25 and 55 years of age, the age-sex–adjusted death rate from natural causes was 15.4 deaths per 1000 person-years (95% CI, 0.2-30.5) in participants with youth-onset diabetes mellitus and 7.3 deaths per 1000 person-years (95% CI, 5.9-8.7) in individuals with older-onset diabetes mellitus (death rate ratio, 2.1; 95% CI, 0.8-5.7). Compared with nondiabetic participants, the death rate was 3.0 times as high in individuals with youth-onset diabetes mellitus (95% CI, 1.1-8.0) and 1.4 times as high in individuals with older-onset diabetes mellitus (95% CI, 1.1-1.8). In a subset of 1386 participants with complete data for all covariates who were observed from the onset of diabetes mellitus, the age at onset of diabetes mellitus was not associated with the incidence of ESRD (hazard ratio, 1.0; 95% CI, 0.9-1.2) after adjusting for sex, mean arterial pressure, body mass index (calculated as weight in kilograms divided by height in meters squared), plasma glucose concentration, smoking, hypoglycemic medicines, and blood pressure medicines in a Cox proportional-hazards model.
Conclusions Early-onset type 2 diabetes mellitus is associated with substantially increased incidence of ESRD and mortality in middle age. The longer duration of diabetes mellitus by middle age in individuals diagnosed younger than age 20 years largely accounts for these outcomes.
Author Affiliations: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Ariz (Drs Pavkov, Bennett, Knowler, Krakoff, Sievers, and Nelson).
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