ERYTHROCYTE SODIUM-LITHIUM COUNTERTRANSPORT ACTIVITY AND TOTAL-BODY INSULIN-MEDIATED GLUCOSE DISPOSAL IN NORMOALBUMINURIC NORMOTENSIVE TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS

Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodium-lithium countertransport in 41 normotensive (mean blood pressure 120/74 mm Hg), normoalbuminuric (mean albumin excretion 6.2 mug/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li . h-1 . l erythrocytes-1 (range 0.07-0.69). Nine patients had values above 0.40 mmol Li . h-1 . l erythrocytes-1 (0.51 +/- 0.10 mmol Li . h-1 . l erythrocytes-1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA1 and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U . kg-1 . h-1: blood glucose clamped at 7.0 mmol/1). The free insulin levels were comparable between the patients with high and nor mal erythrocyte sodium-lithium countertransport (37.2 +/-14.7 mU/l and 34.7 +/- 17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1 +/- 1.5 (range 0.8-6.8) mg . kg-1 . min-1. Erythrocyte sodium-lithium countertransport did not correlate with insulin-mediated glucose disposal in all 41 cases (r(s) = - 0.14), but when the matched groups were compared, patients with raised erythrocyte sodium-lithium countertransport had lower insulin-mediated glucose disposal rates compared to those with normal erythrocyte sodium-lithium countertransport (2.7 +/- 1.1 vs 3.9 +/- 1.3 mg . kg-1 . min-1; p = 0.044). In these 18 patients a significant inverse relationship was found between erythrocyte sodium-lithium countertransport and insulin-mediated glucose disposal (r(s) = - 0.62; p = 0.003). Raised erythrocyte sodium-lithium countertransport appears to be associated with insulin insensitivity in Type 1 diabetes, even in the absence of hyperlipidaemia, hypertension and nephropathy.