N-Acetylation and hydroxylation polymorphisms in type II diabetics with microvascular disturbances

Abstract

The N-acetylation and hydroxylation (CYP2D6) genetic polymorphisms were assessed in 43 healthy subjects and in 84 type II (non-insulin-dependent) diabetics. The proportions of slow and fast acetylators as well as poor and extensive metabolisers in a group of diabetics suffering from microvascular disturbances (nephropathy, retinopathy and neuropathy) were compared with the ocntrol group and with diabetics without such ocmplications. Sulphadimidine was used as a probe for polymorphic acetylation and debrisoqine for CYP2D6. Debrisoquine and its 4-OH metabolite were assayed by means of HPLC, and sulphadimidine using a modified Bratton-Marshall proceedure. The frequency of the slow phenotype (63%) was significantly higher in diabetics with microvascular disturbances than in patiens without diabetic complica tions (P < 0.005). In patients with type II diabetes (84), only the extensive phenotype of hydroxylation was observed.