Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring

Many mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel consumption could be diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes were fed betel nut in standard feed for 2–6 days. Single point (90 min) intra-peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6 months of age. Glucose intolerance was defined as over 3 SD above mean control values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult mice which were fed the betel diet (p<0.01). Studies on the progeny of these mice are presented separately for animals studied in Aberdeen (Group 1) and London (Group 2). In matings of Group 1 betel-fed parents glucose intolerance was found in 4 of 25 male and 1 of 22 female F1 offspring, with significant hyperglycaemia in F1 males born to hyperglycaemic but not to normoglycaemic mothers (p<0.01). In the F2 generation 4 of 23 males and 1 of 16 females and in the F3 generation 1 of 16 males and 0 of 20 females were glucose intolerant. In the Group 2 studies where betel-fed parents were mated to normal controls glucose intolerance was found in 10 of 35 male and 10 of 33 female Fl progeny (p<0.005), and mean islet areas were increased in offspring of betel-fed parents (p<0.001). The total incidence of glucose intolerance in Fl progeny from studies in Groups 1 and 2 was 14 of 60 males and 11 of 55 females (p<0.005). Insulin dependence did not develop in the glucose-intolerant betel-fed animals or their descendants; affected animals appearing well built and active. The development of glucose intolerance in F1 offspring was not dependent on maternal glucose intolerance or on maternal betel-feeding, and 90-min glucose levels of F1 offspring were directly related to paternal but not to maternal glycaemia (p<0.01). Our findings suggest that betelnut (Areca) consumption may be diabetogenic and induce an inheritable abnormality. The hypothesis is of interest in view of the widespread habit of betel consumption and of the strategies known to inhibit the induction of experimental diabetes by diabetogenic nitroso compounds.