Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects

Abstract

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min−1 m−2 for 2 h and the plasma glucose concentration was ‘clamped’ at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects. 2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness. 3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater. 4. The hormonal background to this picture of insulin resistance was not striking: the injured patients showed small elevations in plasma cortisol, glucagon and noradrenaline concentrations, but not in plasma adrenaline concentration. 5. It is concluded that the insulin resistance after injury reflects both diminished responsiveness and diminished sensitivity, affects both fat and carbohydrate metabolism, and must be explained by factors other than the usually considered ‘counter-regulatory’ hormones.