Association between chlorpropamide-alcohol flushing and fast acetylator phenotype in type I and type II diabetes

Abstract

Different prevalences of chlorpropamide alcohol flushing (CPAF) have been reported by different authors in either type I or type II diabetics or in normal subjects and this could be due to different methodological approaches or to different criteria of evaluation of CPAF. Previous studies in small series of patients have also suggested the existence of an association between type I diabetes and the fast acetylator phenotype (AP). The first aim of this study was to find reliable criteria for the assessment of CPAF. The second was to evaluate the prevalence of CPAF and of AP in a large series of type I and type II diabetics; and the third was to evaluate possible associations of CPAF and AP. AP and CPAF were evaluated separately in 256 diabetics (110 with type I and 146 with type II diabetes) and in 183 diabetics (74 with type I and 109 with type II diabetes), respectively. In 156 of these subjects, the two markers were evaluated together. The occurrence of CPAF was studied by subjective and objective assessment and by thermographic recording; CPAF was quantified by the differential value of skin temperature increase [delta T(C-P)] and by the value of differential speed of ascent, expressed in angle-degrees [delta a(C-P)], after treatment with placebo and with chlorpropamide. The fast AP was more frequent in type I than in type II diabetics, was not related to family history of diabetes, sex of the patients, age at onset and duration of diabetes or metabolic control. The most reliable assessment of CPAF was represented by thermographic recording of speed of ascent of skin temperature. CPAF was more frequent in females than in males, more frequent in diabetics than in healthy controls, similarly frequent in type I and in type II diabetes and showed no relationship with family history of diabetes, age at onset, duration of diabetes or metabolic control. An association between fast AP and CPAF was found in type II, but not in type I diabetics: fast acetylators were more frequently CPAF-positive, while slow acetylators were more frequently CPAF-negative. In addition, a linear relationship was found between rate of acetylation and speed of ascent of facial skin temperature after chlorpropamide and alcohol in type II diabetics, not in type I diabetics. The meaning of this association is not clear and deserves further investigations.