Metabolic abnormalities during combined sulphonylurea and phenformin therapy in maturity-onset diabetics

Abstract

Twelve hour metabolic rhythms have been determined in two groups of subjects during combined therapy with a sulphonylurea and phenformin 50 mg twice daily. Subjects with clinical evidence of complications of diabetes showed greater abnormalities in concentrations of blood intermediary metabolites than a group of subjects without complications despite similar mean blood glucose concentrations in the two groups (7.6 mmol/1 with complications; 7.3 mmol/1 without complications). Mean blood lactate (1.93 mmol/1 v 1.39 mmol/l), alanine (0.56 mmol/1 v 0.43 mmol/1), total blood ketone bodies (0.20mmol/l v 0.14mmol/1) and several other intermediary metabolites and their ratios were significantly higher in the group with diabetic complications. It is suggested that the differences between the two groups may arise from impaired disposal of phenformin leading to higher blood concentrations in the group with diabetic complications, despite normal liver function tests and plasma creatinine concentration. It is probable that this accumulation of phenformin results in more pronounced effect upon blood glucose and other intermediary metabolites. Thus, the metabolic abnormalities previously reported in patients treated by phenformin alone are also present during combined sulphonylurea and phenformin therapy, and in the presence of diabetic microangiopathy these abnormalities are accentuated.

The effect of diet on intermediary metabolite concentrations in type 2 (non-insulin-dependent) diabetes mellitus

“…Little attention has been paid, however, to abnormalities of other intermediary metabolites in untreated Type 2 diabetic patients and the response of these to treatment. In previous studies of Type 2 diabetic patients treated with sulphonylureas [4] or biguanide therapy [5,6], abnormalities of circulating intermediary metabolite concentrations were found, although the therapeutic and prognostic importance of these abnormalities is not known [7]. We have studied the response of blood concentrations of the gluconeogenic precursors, lactate, pyruvate, alanine and glycerol, and the ketone body, 3-hydroxybutyrate, in Type 2 diabetic patients for 4 h following a standard breakfast, at diagnosis and following correction of hyperglycaemia by a period of diet.…”