Changing course of diabetic nephropathy in the Pima Indians

Abstract

Pima Indians from the Gila River Indian Community in Arizona have a high incidence rate of type 2 diabetes, and kidney disease attributable to diabetes is a major cause of morbidity and mortality in this population. Since 1965, each member of the population at least 5 years of age is invited to participate in a research examination every other year. During the past 43 years, the overall incidence of diabetes in the Pima Indians has not changed, but the incidence of diabetes among those less than 15 years of age has increased nearly 6-fold, as an increasing prevalence and degree of obesity in the youth have shifted the onset of diabetes to younger ages. The rising frequency of diabetes in the youth has led, in turn, to the emergence in mid-life of the major complications of diabetes, including kidney disease. On the other hand, the introduction and widespread use of medicines to control blood pressure, reduce hyperglycemia, and block the renin-angiotensin system (RAS) have lead to improvements in the average blood pressure and glycosylated hemoglobin levels in the diabetic population. These countervailing forces have influenced the course of diabetic nephropathy in a generally favorable direction in the past few years, as evidenced by the decline in the overall incidence of end-stage kidney disease since 1990. A continued increase in the incidence of type 2 diabetes in youth, however, threatens to reverse this trend.

Figure 1

Mean BMI in nondiabetic Pima Indians by age, sex, and time period. The numbers below each graph represent the percent increase in mean BMI between the first and the third time period according to age group. Reprinted with permission [6].

Figure 2

(A) Age-specific, sex-adjusted incidence rates of type 2 diabetes in three time periods. In each period, sex-adjusted incidence rates increased up to 55–64 years and then declined. (B) Incidence rate ratios (IRR) relative to the first time period. IRR2=incidence rate ratios in the second relative to the first period, IRR3=incidence rate ratios in the third relative to the first period. * p_trend<0.05. Reprinted with permission [6].

Figure 3

(a) Age-sex-adjusted incidence rates of end-stage kidney disease, defined by deaths from diabetic nephropathy (DN) and renal replacement therapy (RRT), in type 2 diabetic Pima Indians ≥ 25 years old. Incidence rates are calculated for 4-year intervals between 1967 and 2002. The number on top of each bar represents new cases of end-stage kidney disease. The combined height of the two bars represents the total incidence of end-stage kidney disease. (b) Sex-adjusted incidence of diabetic end-stage kidney disease for 9 4-year intervals, by age group. Reprinted with permission [14].

Figure 4

Sex-adjusted incidence (95% CI) of diabetic end-stage kidney disease by onset of diabetes and age group. Adapted with permission [31].