Objective: 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.
Research design and methods: 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.
Results: 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).
Conclusions: 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.