KINETIC-BEHAVIOR OF THE ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORTERIN NONNEPHROPATHIC DIABETIC TWINS

Elevated erythrocyte sodium-lithium countertransport activity occurs i n diabetes and may be genetically mediated. The relation of this abnor mality to the disease and its complications is unclear. To remove conf ounding genetic factors and the impact of complications, we studied so dium-lithium countertransport activity together with its kinetic compo nents, maximal rate of turnover (V-max) and external affinity for sodi um (k(Na)), in identical-twin pairs discordant for insulin-dependent d iabetes who were normotensive and had no evidence of nephropathy. Fift een twin pairs were studied along with the same number of healthy cont rol subjects matched with the twins for gender, age, and body mass ind ex. Clinical and laboratory characteristics of the twins and controls were similar, with the exception that whole blood glucose and glycated hemoglobin concentrations were higher in diabetic twins (P < .001). C omparison of countertransport activity between nondiabetic and diabeti c twin groups failed to uncover any significant differences (P = .30, Wilcoxon). Similarly, there were no differences in countertransport ac tivity between the nondiabetic twin group and the controls (P = .38, M ann-Whitney). Furthermore, no associations were noted between residual activity values and residual data of any of the other clinical or lab oratory characteristics measured. Comparison of V-max between nondiabe tic and diabetic twin groups showed a significant elevation in the dia betic twins (0.515 + 0.220 v 0.439 + 0.229 mmol Li/L RBC . h, P = .049 , paired t test). By contrast, no significant differences were noted b etween the nondiabetic twin group and the controls (P = .15, unpaired t test). Comparison of k(Na) between nondiabetic and diabetic twin gro ups found no significant differences in k(Na) (P = .42, Wilcoxon). Sim ilarly, there were no differences in k(Na) between nondiabetic twins a nd controls (P = .14, Mann-Whitney). Neither the residual data for V-m ax nor k(Na) showed any association with the residual data of any of t he other clinical or laboratory characteristics measured. When intertw in correlations were examined, all three parameters describing the beh avior of the sodium-lithium countertransporter showed significant inte rtwin correlations (activity, r = .51, P = .04; V-max, r = .82, P = .0 01; k(Na), r = .76, P = .001). In conclusion, the diabetic state has a small effect on the V-max of the sodium-lithium countertransporter. F ailure to consider the complex nature of the activity measurement is l ikely to have been partly responsible for earlier confusion with regar d to the effect of diabetes on the countertransporter, since experimen tal conditions varied between studies and individual kinetic component s were not measured. The associations between twins in this study with respect to V-max and k(Na) indicate a genetic influence on both const ants of the countertransporter. V-max appears also to be sensitive to certain as yet unidentified environmental factors. Copyright (C) 1996 by W.B. Saunders Company