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 (Are ca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel c onsumption could be diabetogenic. Young adult CD1 mice with a low spon taneous incidence of diabetes were fed betel nut in standard feed for 2-6 days. Single point (90 min) intra-peritoneal glucose tolerance tes ts were used to follow glucose tolerance up to 6 months of age. Glucos e intolerance was defined as over 3 SD above mean control values. Gluc ose intolerance was found in 3 of 51 male and 4 of 33 female adult mic e which were fed the betel diet (p < 0.01). Studies on the progeny of these mice are presented separately for animals studied in Aberdeen (G roup 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 of fspring, with significant hyperglycaemia in F1 males born to hyperglyc aemic but not to normoglycaemic mothers (p < 0.01). In the F2 generati on 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 stud ies where betel-fed parents were mated to normal controls glucose into lerance was found in 10 of 35 male and 10 of 33 female F1 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 F1 progeny from studies in Groups 1 and 2 was 14 of 60 males and 11 of 5 5 females (p < 0.005). Insulin dependence did not develop in the gluco se-intolerant betel-fed animals or their descendants; affected animals appearing well built and active. The development of glucose intoleran ce in F1 offspring was not dependent on maternal glucose intolerance o r 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 betel-nut (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 o f the strategies known to inhibit the induction of experimental diabet es by diabetogenic nitroso compounds.