Inter-relationship between insulin secretion and plasma free fatty acid and triglyceride transport kinetics in maturity onset diabetes and the effect of phenethylbiguanide (phenformin).

Abstract

The plasma free fatty acid and triglyceride transport kinetics in 16 non-obese and 7 obese maturity onset diabetics with hypertriglyceridaemia have been compared with results obtained in 27 control subjects. Changes in glucose and insulin responses were evaluated in relation to the lipid parameters. All the diabetics showed elevated plasma FFA levels and turnover rates. In the non-obese diabetics the plasma triglyceride turnover rate was within the normal range and their hypertriglyceridaemia was due to impaired triglceride clearance. In the obese diabetics the plasma triglyceride turnover rate was increased and they also had some impairment of triglyceride clearance, so that in them a double mechanism was observed to account for their hypertriglyceridaemia. The insulin levels in the diabetics were similar to, or greater than, those found in the controls. Our results suggested that the enhanced lipolysis and impaired triglyceride clearance observed in the diabetic patients were a manifestation of insulin unresponsiveness in adipose tissue and that the changes in insulin and glucose relationship could be secondary to elevated FFA and triglyceride levels. Further confirmation was obtained by the finding of an exaggerated insulin response to a glucose challenge in normal subjects infused with Intralipid. Treatment with phenethylbiguanide (Phenformin) significantly lowered the plasma FFA and triglyceride concentration in both diabetic groups. This was associated with normalisation of both plasma FFA turnover and triglyceride clearance. It also reduced the triglyceride turnover rate to the normal range in the obese diabetics. These changes were associated with a fall of plasma glucose and insulin levels to within the normal range. These results suggested an effect of Phenformin in reducing the rate of lipolysis leading to improved glucose tolerance.