The effect of phenformin on the induction of plasma triglyceride by high-carbohydrate feeding was studied in ten subjects (nine normals and one Type II, hyperlipoproteinemia). Each study was divided into four periods. During periods I and III, each subject received an American Diabetes Association diet calculated to maintain body weight and in periods II and IV a high-carbohydrate diet (85 per cent of the calories derived from carbohydrate) which was isocaloric with the control diet. Phenformin, 50 mg. twice daily, was administered in either period II or IV in association with the high-carbohydrate diet. There was no change in weight during the study. The plasma triglyceride increase (ΔTG) during the high-carbohydrate diet alone was 103 mg. per cent as compared with a ΔTG of 26 mg. per cent during the high carbohydrate-phenformin period, a highly significant difference (p < 0.005).
Insulin secretion and glucose tolerance during each period was determined by the sum of the increments above base baseline of plasma insulin and glucose concentrations during a five-hour oral glucose tolerance test. No significant differences in glucose tolerance or in insulin secretion occurred during any of the periods despite the alterations produced by the high-carbohydrate diet and phenformin in plasma triglyceride concentrations. A slight correlation could be demonstrated between the insulin response to a glucose load while on the control diet and the magnitude of the triglyceride response on the high-carbohydrate diet. The data indicate that (1) phenformin inhibits the induction of plasma triglyceride produced by carbohydrate loading, (2) there was no correlation between the changes in plasma triglyceride concentrations, glucose tolerance or insulin responsiveness during the experimental periods and (3) the magnitude of the increase in plasma triglyceride concentration may be related to the insulin response to a glucose load during the control period.