The effects of diabetes mellitus, exercise, and single doses of biguanides upon lactate metabolism in man.

The polymorphism of phenformin oxidation has been investigated in 103 non-insulin-dependent (Type II) diabetics. The frequency distribution was clearly bimodal and 14 poor metabolisers were identified. The frequency of the recessive allele (0.369) was not significantly different from that found previously in non-diabetics. Six of the extensive metabolisers of phenformin were matched for age, sex and oxidizer phenotype with non-diabetic controls. All subjects underwent a standard 3-min exercise test, using a bicycle ergometer, after which plasma lactate concentration was monitored for 90 min. There was no significant difference between groups in lactate accumulation or elimination. Ten extensive metabolisers, ten poor metabolisers and seven non-diabetics (matched for age, sex and phenotype with seven of the diabetic extensive metabolisers) were challenged with a fasting oral dose of phenformin (50 mg), after which plasma lactate, and blood pyruvate and glucose concentrations were monitored for 4 h. A further ten diabetics (five extensive and five poor metabolisers of phenformin) received a single dose of metformin (1 g) following an identical protocol. No significant changes were observed in any group.