The metabolic and hormonal effects of continuous subcutaneous insulin infusion therapy in diabetic children

Summary To find out whether the concurrent metabolic and hormonal abnormalities are corrected when normoglycaemia is achieved, two groups of diabetic children (newly-diagnosed and chronically-treated) were treated with insulin pumps. Fasting levels of metabolites, lipids and hormones were measured before and after 8 to 10 days of pump treatment and the immediate postprandial hormonal and metabolic changes after a test-meal were also measured. Restoration of normoglycaemia was accompanied by correction of multiple metabolic abnormalities including the normalisation of fasting plasma free insulin, growth hormone, free fatty acid, triglyceride and total cholesterol levels. Plasma glucagon, however, decreased below normal, and significant hypoketonaemia developed in newly-diagnosed diabetic children. The fall in (VLDL+LDL)-cholesterol levels was accompanied by a substantial increase in HDL₂-cholesterol concentration in newly-diagnosed diabetic children, whereas pump-treatment resulted in a decrease of the HDL₃-cholesterol subfraction in chronically-treated diabetic children. The postprandial blood glucose and free insulin profiles were similar to that of control subjects, but there was an abnormal postmeal fall in plasma glucagon and free fatty acid levels. These changes together with the fasting hypoglucagonaemia and hypoketonaemia indirectly suggest that optimal glycaemic control is only achievable at the expense of increased insulin action despite the failure to detect peripheral hyperinsulinaemia. Furthermore, the restoration of normoglycaemia and the simultaneous normalisation of the metabolic and endocrine milieu is not entirely possible with this mode of therapy.