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 F1 progeny (p < 0.005), and mean islet areas were increased in offspring of betel-fed parents (p < 0.001).

To investigate the antidiabetic effect of betel-nut from Areca catechu

Increased waist size and weight in relation to consumption of Areca catechu (betel-nut); a risk factor for increased glycaemia in Asians in east London

Academic Medical Unit, St Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary Westfield College, UK

Type 2 diabetes is commoner in Asians than Caucasians. Many nitrosamines are diabetogenic, causing both type 2 and type 1 diabetes. Of CD1 mice fed with betel-nut or associated nitrosamines 8.5% develop glucose intolerance with marked obesity. Glycaemia and anthropometric risk markers for type 2 diabetes were therefore examined in relation to betel usage in 993 'healthy' Bangladeshis by one bilingual research-worker (N.M.). Of these, 12% had known diabetes. A further 145 of 187 subjects 'at-risk' of diabetes (spot glucose > 6.5 mmol/l < 2 h after food, or > 4.5 mmol/l > 2 h after food) had a second blood glucose sample taken; sixty-one were confirmed as 'at-risk', and had an oral glucose tolerance test; nine new diabetics were identified. Multiple regression analysis showed that spot blood glucose values decreased with time after eating (P = 0.0005) and increased independently with waist size (P = 0.0005) and age (P = 0.0005) without relationships to other aspects of the diet, season or smoking. Waist size was strongly related to betel usage independent of other factors such as age. Betel use interacted with sex, relating to increasing glycaemia only in females. Since waist and age were the major markers of increasing glycaemia we suggest that betel chewing, a habit common to about 10% of the world population (more than 200 million people) may contribute to the risk of developing type 2 diabetes mellitus.