Poor metabolic control and predisposition to hypertension, rather than hypertension itself, are risk factors for nephropathy in type 2 diabetes

Abstract

Sodium-lithium countertransport (Na+/ Li+ CT) activity in erythrocytes has been shown to be high in a subset of patients with essential but not secondary hypertension and in type 1 (insulin-dependent) diabetic patients with nephropathy. More recently it has been shown that the presence of a major gene for Na+/Li+ CT, or another closely linked gene, rather than the actual level of Na+/Li+ CT, increases the risk of hypertension onset. The aim of the present study was to investigate whether Na+/Li+ CT activity is associated with hypertension and nephropathy in type 2 (non-insulin-dependent) diabetes. We studied 18 type 2 diabetic patients with normal blood pressure levels (systolic ≤140 and diastolic ≤85 mmHg) and albumin excretion rate (≤15 μg/min), 19 type 2 diabetic patients with hypertension (systolic ≥145 and diastolic ≥90 mmHg) and a normal albumin excretion rate (≤15 μg/min) and 19 type 2 diabetic patients with an increased albumin excretion rate (≤20 μg/min), irrespective of blood pressure levels. Eighteen normal subjects, matched for sex and age, served as controls. Na+/Li+ CT activity in erythrocytes was higher in type 2 diabetics with a high albumin excretion rate (486±148 μmol/l erythrocytes per hour,P<0.01) and in hypertensive diabetics (410±129,P<0.05), but not in normotensive diabetics (340±141), than in controls (282±96) (mean±SD). Body mass index was higher in diabetics with hypertension and in those with an abnormal albumin excretion rate than in normotensive diabetics and controls. Blood pressure levels were higher in diabetic patients with an increased albumin excretion rate than in normotensive diabetics and controls. Of diabetic patients with a high albumin excretion rate 26% had normal diastolic blood pressure levels. Diabetics with a high albumin excretion rate had higher glycated haemoglobin, cholesterol and triglyceride levels and a longer duration of diabetes than hypertensive diabetics with a normal albumin excretion rate. The association of these clinical features in type 2 diabetes closely resembles that previously reported in type 1 diabetes. A novel finding of the present study is that predisposition to hypertension, as indicated by high Na+/Li+ CT, seems to confer a susceptibility to the development of renal damage in type 2 diabetes, partially independent of blood pressure levels per se, and that diabetic patients with high Na+/Li+ CT and hypertension are, to some extent, protected against the development of nephropathy when the metabolic control is tighter and the duration of the disease shorter.