The physiological effects of insulin-induced hypoglycaemia in man: responses at differing levels of blood glucose.

The aim of this study was to describe hormonal, cardiovascular and thermoregulatory responses to insulin-induced hypoglycaemia of differing levels of severity. Five normal male volunteers were rendered hypoglycaemic at intervals of 1 week by intravenous infusions of 3, 4 or 6 units of insulin/h, or by intravenous injection of 0.15 unit/kg body weight. Plasma glucose reached nadir values of 2.08 +/- 0.10, 1.82 +/- 0.21, 1.24 +/- 0.08 and 0.92 +/- 0.06 mmol/l (means +/- SEM) in the four experiments. Non-esterified fatty acid levels fell equally in all experiments but recovery was more rapid with severe hypoglycaemia. In contrast the rate of recovery of plasma glucose was slower with deeper hypoglycaemia and this appeared unrelated to the counter-regulatory response. Plasma glucagon, adrenaline and prolactin levels increased in proportion to the severity of hypoglycaemia, but peak concentrations of cortisol, growth hormone (somatotropin) and noradrenaline did not vary, suggesting that moderate hypoglycaemia had elicited maximal responses. When the areas under the curves were calculated, the cortisol responses were greater for the 6 units infusion and bolus injection than for the other infusions, and the growth hormone responses were similar for all three infusions but significantly greater with the bolus injection. Increases in heart rate and systolic blood pressure were related to the severity of hypoglycaemia, but changes in diastolic blood pressure and peripheral vascular resistance (assessed from calf and from hand blood flow) were not. Central temperature fell by 0.13 +/- 0.06 degrees C, 0.30 +/- 0.10 degrees C, 0.65 +/- 0.14 degrees C and 1.15 +/- 0.30 degrees C (means +/- SEM) in the four experiments, and the fall in skin temperature had a similar gradation. Many physiological responses to hypoglycaemia are not 'all-or-none', but vary according to the intensity of stimulus; some are already maximal at mild degrees of hypoglycaemia. Other changes are more complex, reflecting an interplay between opposing endocrine and neural responses.