Effect of Chronic ACE Inhibition on Glucose Tolerance and Insulin Sensitivity in Hypertensive Type 2 Diabetic Patients

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Abstract
The question, of whether long-term treatment of essential hypertension with angiotensin-converting enzyme (ACE) inhibitors is capable of modifying glucose tolerance or insulin sensitivity in Type 2 (non-insulin dependent) diabetes, is still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period and again after 3 months of antihypertensive treatment with the ACE inhibitor, Captopril. Glucose tolerance was tested with a 75-g oral glucose load and insulin sensitivity was measured by the insulin suppression test, while dietary and drug treatment of the diabetes remained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 ± 3 mmHg to a final value of 115 ± 2 mmHg (p < 0.005); in six patients, the change in MBP was < 5 mmHg (non-responders), thus giving a clinical response rate of ˜60%. After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycated haemoglobin concentrations were unchanged from baseline. During the oral glucose tolerance test, the incremental glucose area-under-curve was 0.75 ± 0.05 mol 120 min I−1 before and 0.76 ± 0.06 mol 120 min I−1 after treatment (p = ns). Endogenous insulin response and suppression of plasma FFA levels were superimposable on the two occasions. During the insulin suppression test, steady-state plasma glucose levels were 14.4 ± 1.3 vs 14.2 ±1.1 mmol I−1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 ± 21 vs 287 ± 14 pmol I−1). Neither endogenous (oral glucose) nor exogenous (insulin suppression test) insulin caused any change in plasma potassium concentrations. This resistance to the hypokalemic action of insulin was not affected by Captopril. The eight blood pressure responders, or the seven patients with less fasting hyperglycaemia, had similar baseline characteristics as the whole group, and likewise showed no significant treatment-related change in glucose tolerance or insulin sensitivity. We conclude that chronic ACE inhibition does not change glucose tolerance, endogenous insulin response, and sensitivity of glucose disposal, lipolysis, and potassium metabolism to insulin in stable Type 2 diabetic patients whose glycaemic control by other means (diet and/or drugs) is held constant.