POOR METABOLIC CONTROL AND PREDISPOSITION TO HYPERTENSION, RATHER THAN HYPERTENSION ITSELF, ARE RISK-FACTORS FOR NEPHROPATHY IN TYPE-2 DIABETES

Sodium-lithium countertransport (Na+/Li+ CT) activity in erythrocytes has been shown to be high in a subset of patients with essential but n ot secondary hypertension and in type 1 (insulin-dependent) diabetic p atients with nephropathy. More recently it has been shown that the pre sence 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 hype rtension onset. The aim of the present study was to investigate whethe r Na+/Li+ CT activity is associated with hypertension and nephropathy in type 2 (non-insulin-dependent) diabetes. We studied 18 type 2 diabe tic patients with normal blood pressure levels (systolic less-than-or- equal-to 140 and diastolic less-than-or-equal-to 85 mmHg) and albumin excretion rate (less-than-or-equal-to 15 mug/min), 19 type 2 diabetic patients with hypertension (systolic greater-than-or-equal-to 145 and diastolic greater-than-or-equal-to 90 mmHg) and a normal albumin excre tion rate (less-than-or-equal-to 15 mug/min) and 19 type 2 diabetic pa tients with an increased albumin excretion rate (greater-than-or-equal -to 20 mug/min), irrespective of blood pressure levels. Eighteen norma l subjects, matched for sex and age, served as controls. Na+/Li+ CT ac tivity in erythrocytes was higher in type 2 diabetics with a high albu min excretion rate (486 +/- 148 mumol/l erythrocytes per hour, P<0.01) and in hypertensive diabetics (410 +/- 129, P<0.05), but not in normo tensive 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 excr etion rate 26% had normal diastolic blood pressure levels. Diabetics w ith a high albumin excretion rate had higher glycated haemoglobin, cho lesterol and triglyceride levels and a longer duration of diabetes tha n hypertensive diabetics with a normal albumin excretion rate. The ass ociation of these clinical features in type 2 diabetes closely resembl es 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 pre ssure levels per se, and that diabetic patients with high Na+/Li+ CT a nd hypertension are, to some extent, protected against the development of nephropathy when the metabolic control is tighter and the duration of the disease shorter.