Effects of Acute Endotoxemia on Glucoregulation in Normal and Diabetic Subjects

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Abstract
Response to the endotoxin, Pseudomonas polysaccharide, (Piromen®) was used as a model for infection induced insulin resistance in seven control subjects and seven juvenile diabetics. All subjects had iv GTTs with measurement of several glucoregulatory hormones on 3 successive days: GTT–1; GTT–2, 3 h after Piromen (0.6 µg/kg), and GTT–3. A continuing iv infusion delivering 0.5 to 4.0 units of regular insulin/h was given to the diabetic subjects throughout the entire study period. Doses were adjusted so as to maintain mean plasma glucose concentrations between 120 and 220 mg/dl. However, the insulin infusion dose during each iv GTT was kept constant at 0.5 units/h. Following endotoxin the control subjects developed fasting hyperglycemia, mild glucose intolerance, basal and glucose stimulated hyperinsulinemia, hyperglucagonemia, and elevated plasma levels of growth hormone, ACTH, and cortisol. In the diabetic subjects given endotoxin, basal glucose values and those following iv GTT–2 were unchanged from comparable values during GTT–1, although plasma glucagon, growth hormone, cortisol and ACTH all became significantly elevated. The diabetics required 31% more insulin on the endotoxin day than the control day (P < .002) despite the fact that glucose values were 83% higher on the endotoxin day. The continuous infusion of insulin following the stress of acute endotoxemia prevented further deterioration in glucose tolerance in diabetic subjects and was also associated with a blunting of growth hormone responses in the diabetics (as compared to controls).