Isotope turnover studies in uncontrolled diabetes and the effects of insulin

Turnover rates of glucose, free fatty acids (FFA) and leucine have been measured in newly diagnosed, uncontrolled insulin-dependent diabetic (IDD) patients. The results have been compared with data collected from the same patients while on conventional insulin therapy as well as after overnight intravenous infusion of insulin with sustained normoglycaemia. The data have been analysed by compartmental and non-compartmental methods and the results have been compared with simultaneously collected data on respiratory exchange. Oxidation rates of 14C-labelled substrates have also been measured. Tracer studies were done on established diabetics after insulin withdrawal and subsequent intravenous infusion of insulin at different rates. The results confirm the in vivo importance of the glucose-fatty acid cycle, indicating that when glucose, FFA and ketone bodies are available in excess it is FFA and ketones that are metabolized in preference to glucose. The data emphasize the importance of increased production rates rather than decreased utilization rates in producing high concentrations of substrates in the plasma of insulin-deficient patients.