Abstract

The aims of this study were to examine genetic and environmental influences in the development of early diabetic nephropathy and to assess the value of measuring membrane sodium transport as a marker for early nephropathy. We measured erythrocyte sodium-lithium (Na-Li) countertransport, blood pressure (BP), HbA1c, and microalbuminuria (MA) in 84 adolescents with insulin-dependent diabetes mellitus (IDDM), 29 of whom had MA. Twenty-nine non-MA patients were selected and matched for age, sex, and IDDM duration with the 29 diabetic subjects with MA. The 84 diabetic adolescents were also compared with 85 nondiabetic siblings. The erythrocyte Na-Li countertransport was significantly greater in the IDDM group than in the sibling group (mean +/- SD, 0.41 +/- 0.14 vs. 0.30 +/- 0.11 mmol Li.liters of erythrocytes-1.h-1, respectively, P < 0.0001), but a significant correlation was noted between the results in IDDM subjects and their siblings (r = 0.42, P < 0.0008). Na-Li countertransport was not different in the diabetic subjects with or without MA (0.43 +/- 0.13 vs. 0.37 +/- 0.13 mmol Li.liters of erythrocytes-1.h-1, respectively). There was a significant correlation in the IDDM group between recent diabetic control (HbA1c) and Na-Li countertransport (r = 0.37, P < 0.003). Diastolic BP was significantly higher in the IDDM group with MA than in those without MA (60 +/- 6 vs. 55 +/- 6 mmHg, respectively, P < 0.03). These results suggest that erythrocyte Na-Li countertransport is influenced by the diabetic milieu. However, there was also evidence in our subjects of a genetic contribution to Na-Li countertransport as seen by the correlation between levels in the IDDM subjects and their siblings. Using Na-Li countertransport, we were not able to segregate those IDDM adolescents with and without early nephropathy.

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