Insulin Action in Insulin-Dependent Diabetics After Short-Term Thiazide Therapy

The influence of short-term thiazide treatment on peripheral tissue and liver sensitivity to insulin in insulin-dependent diabetes mellitus was determined by the euglycemic insulin clamp technique. A sequential three-step hyperinsulinemic clamp was performed in six insulin-dependent diabetics before and after 2 wk of hydroflumethiazide (HFT) administration in a daily dose of 75 mg. Insulin was infused at rates of 0.5, 2.0, and 4.0 mU · kg−1 · min−1, and each dose was given for at least 120 min. Glucose uptake during the last 30 min of each step was almost identical in the two situations (2.7 ± 0.6 vs.2.4±0.5mg · kg−1 min−1, 9.6 ± 0.9 vs. 9.7 ± 1.2 mg · kg−1 · min−1, and 12.0 ± 1.3 vs. 12.6 ± 1.5 min−1). Serum insulin levels were also similar, and blood glucose was kept at 100 ± 3, 2.4 ± 0.5 mg · kg−1 99 ± 4, and 97 ± 3 mg/dl before thiazides and at 93 ± 6, 93 ± 6, and 94 ± 6 mg/dl after thiazides. Another five insulin-dependent diabetics were infused with tritiated glucose followed by insulin infusion at two rates: 0.45 and 1.0 mU · kg−1 · min−1. Basal glucose output was comparable before and after thiazides (3.63 ± 0.24 vs. 2.97 ± 0.26 mg · kg−1 · min−1), as was the liver response to increasing insulin concentrations. The metabolic state as assessed by HbA1c and fasting blood glucose did not differ in the two experiments. In conclusion, short-term HFT therapy has no impact on either insulinmediated glucose uptake or sensitivity of the liver to insulin. Thus, probably no adverse effects on the metabolic state will be encountered in diabetics with minimal endogenous insulin during treatment with thiazides.