Early-Onset of Type 2 Diabetes Linked to Early Death

PHOENIX, Ariz., July 25 -- The onset of type 2 diabetes before age 20 in Pima Indians, who are genetically prone to the disease, was associated with an increased risk of early kidney failure and death between ages 25 to 55, according to researchers here.

In a longitudinal study of 1,856 diabetic Pima Indians, including 96 with youth-onset diabetes, the rate of end-stage renal disease was five to eight times higher than those of the same age with older-onset diabetes (ages 25 to 44), reported investigators in the July 26 issue of the Journal of the American Medical Association.

Death rates for participants with early-onset diabetes were three times higher than in non-diabetics and slightly higher than among those with older-onset disease, said Meda Pavkov, M.D., Ph.D., and colleagues, of the National Institute of Diabetes and Digestive and Kidney Diseases.

Among the 1,856 diabetic participants (767 male and 1,089 female), 96 had youth-onset type 2 diabetes and 1,760 had older-onset type 2 diabetes (ages 20 to 55 years). Pima Indians have extremely high rates of type 2 diabetes, and the prevalence of the disease in Pima youth had doubled between 1967 and 1998, the researchers wrote.

The sex-adjusted kidney failure rate for youth-onset diabetes was 8.4 times higher than for those with onset at ages 25 to 34 years, five times higher than for onset at ages 35 to 44 years, and four times higher for onset at 45 to 54, Dr. Pavkov said.

The age-sex-adjusted incidence of diabetic end-stage renal disease was 25.0 cases per 1,000 person-years in youth-onset diabetes (95% confidence interval, 6.7-43.1). In older-onset (25 to 34 years), the incidence was 5.4 cases per 1,000 person-years (CI, 4.4-6.4); incidence rate ratio 4.6 (CI, 2.2-9.8). Age-specific renal-failure incidence rates were higher in participants with youth-onset diabetes at all ages, the researchers reported.

Between ages 25 and 55, the age-sex-adjusted death rate from natural causes was 15.4 deaths per 1,000 person-years in participants with youth-onset diabetes (CI, 0.2-30.5), and 7.3 deaths per 1,000 person-years (CI, 5.9-8.7) in individuals with older-onset diabetes (death rate ratio, 2.1; 95% CI, 0.8-5.7).

To further explore differences in youth-onset and older-onset groups, death rates were compared with those of 4,189 nondiabetic participants. As expected, the nondiabetic subjects had the lowest death rates. Compared with nondiabetic participants, the death rate was 3.0 times as high in individuals with youth-onset diabetes (CI, 1.1-8.0) and 1.4 times as high in individuals with older-onset diabetes (CI, 1.1-1.8).

More than half of the diabetic participants died from diabetic nephropathy, cardiovascular disease, or infections, regardless of the age of onset of diabetes. By contrast, the most prevalent cause of death in the nondiabetic participants was alcoholic liver disease, the researchers reported.

In a subset of 1,386 participants with complete data for all covariates who were observed from the onset of diabetes, the age at onset of diabetes was not associated with the incidence of end-stage renal disease (hazard ratio, 1.0; CI, 0.9-1.2), after adjusting for sex, mean arterial pressure, body mass index, plasma glucose concentration, smoking, hypoglycemic and blood pressure medicines in a Cox proportional-hazards model.

By contrast, the researchers said, natural mortality was 1.7 times as high with each 10-years' increase in the age at onset of diabetes (hazard ratio, 1.7; CI, 1.5-2.0).

Cardiovascular disease is lower in Pima Indians than in the white population, the researchers noted, and occurs most frequently in association with kidney failure. In this study, 48% of the cardiovascular disease deaths occurred in dialysis patients and 32% in those with earlier stages of kidney disease, confirming that it occurs predominantly in persons with kidney disease, regardless of age of onset of diabetes.

The investigators noted that they were not able to assess the effect of puberty on the progression of kidney disease. Also, they said, because follow-up began at 25 years of age, survival bias among the early-onset subjects could influence these findings if early-onset individuals with more severe disease died before reaching age 25.

Although the number of participants with youth-onset diabetes was small, the researchers wrote, these participants were observed for up to 30 years and represent the longest and most complete follow-up of youth-onset type-2 diabetes to date.

The longer duration of diabetes by middle age in those diagnosed younger than 20 years, and not the age at onset per se, is largely responsible for the higher rate of serious complications, Dr. Pavkov said. An equivalent duration of type 2 diabetes in a young person is as damaging to the kidneys as it is in an older person, he added.

Because youth-onset type 2 diabetes leads to substantially increased complications rates and mortality in middle age, "efforts should focus on preventing or delaying the onset of diabetes, delaying the onset of diabetic nephropathy, or both," the researchers concluded.