Short- and long-term glycaemic control and the state of the renin system in type 1 diabetes mellitus

Renin system blockade in diabetes exerts a strong positive influence on complications, especially nephropathy. In hyperglycaemic diabetic subjects, however, blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors results in a marked rise in plasma renin. We investigated whether glycaemic fluctuations measured in hours, or those measured in weeks by Haemoglobin A(1C) (HbA(1C)) , influenced the plasma renin response to captopril. Fifty-four type 1 diabetic subjects were studied in high-salt balance. After an all night fast and in the supine position, baseline serum glucose level was drawn. Iv. glucose and insulin were then administered to keep serum glucose between 100 and 150 mg/dL (target). When target was reached, captopril 25 mg pre os was administered and plasma renin activity (PRA) and finger stick glucose were drawn, then serially every 45 minutes for 225 minutes. Baseline glucose and baseline PRA were drawn hours apart. Peak PRA corresponded to the renin level at peak captopril effect, 90' after administration. Renin response (RR) = peak PRA - baseline PRA. Correlation of baseline glucose with baseline PRA was weak (r=0.3, p=0.02), but strong with peak PRA (r=0.65; p=0.002). Drop in glucose had a weak, negative correlation with baseline PRA (r=-0.3, p=0.03) but a much stronger one with peak PRA (r=-0.7, p<0.0001). After adjustment for baseline PRA and baseline glucose, mean RR correlated strongly with mean drop in glucose (r=-0.72; p=0.008). Conversely, HbA1C correlated with none of the measures of renin system activation (r=0.05;p=0.7). In type 1 diabetic subjects, short-term hyperglycaemia, but not long-term glycaemic control, enhanced the RR to captopril.