Sanjay Kalra  ( Department of Endocrinology, Bharti Hospital, Karnal, India. )
Yatan Pal Singh Balhara  ( Department of Psychiatry, National Drug Dependence Treatment Center, All India Institute of Medical Sciences, New Delhi, India. )

This communication focuses on an important, yet neglected, aspect of medicine, which has an impact on diabetes care as well. Betel quid (paan) chewing is a commonly encountered, socioculturally accepted, "culture-bound" addictive disorder. Betel quid chewing has unwanted psychotropic, carcinogenic and dysmetabolic effects. Thus, it should be discouraged as strongly as tobacco use. This communication calls for raised awareness among physicians and community leaders regarding this addictive disorder, and highlight the need for research on this topic.
Keywords: Drug addiction, drug dependence, metabolic syndrome, South Asia.


Introduction

Betel quid is the fourth most commonly used psychoactive substance in the world, after caffeine, nicotine and alcohol.¹ Betel quid known in many parts of the South Asia as \\\'paan\\\', is an integral part of South Asian culture and cuisine. It is available in different forms, such as \\\'saada, (simple),\\\' meetha\\\' (sweet), \\\'palangtor\\\' (aphrodisiac), and processed (tobacco- free: pan masala; tobacco-rich: gutka).

Dependence

Though its use is socioculturally accepted, betel quid chewing is an addictive behaviour.² Betel quid chewing can foster addiction or dependence similar to that of cigarettes. This addiction is independent of, and not based on, the tobacco content of betel quid.³ Areca nut, the main constituent of betel quid, along with betel leaves, slaked lime and tobacco, contains aromatic alkaloids such as arecoline, arecaidine, guvacine and guvacoline. These compounds bind to GABA receptors, and create a feeling of alertness and wellbeing.²

Carcinogenic Effects

Betel quid use is associated with various precancerous and cancerous lesions, including those of oral cavity, pharynx, esophagus, liver, biliary tract and uterus. This association, too, is independent of the tobacco content in betel quid.⁴ Betel quid is listed as a group I carcinogen by the international Agency for Research on Cancer.⁵

Metabolic Effects

Betel quid has pleiotropic unwanted effects on metabolic and cardiovascular health (Table).

Animal studies have revealed diabetogenic and obesogenic effects of betel nut.⁶ Past betel quid chewing is associated with new onset diabetes,⁷ while betel nut consumption has been shown to be associated with increased waist size (in men and women) and increased glucose levels (in women).⁸
A Bangladeshi cohort study, conducted over 10 years, has reported a greater risk of all-cause mortality and cancer related morality in betel quid chewers. A dose - response relationship of duration and intensity of betel quid use was noted with all-cause mortality. However, no increase in cardiovascular disease was noted in betel quid chewers.⁹
In contrast, a meta analysis of 17 Asian studies, involving 5 cohorts and 12 case control studies, has demonstrated increased risk of obesity, metabolic syndrome, diabetes and cardiovascular disease in betel quid chewers.¹⁰

Other Effects

Apart from its psychoactive, tumorigenic, and dysmetabolic effects, betel quid use impacts health in other ways as well. Betel quid use may predispose to urinary stone disease,¹¹ precipitate chronic kidney disease,¹² contribute to hypovitaminosis D,¹³ and increase risk of infectious disease including HIV/AIDS, dengue fever, tuberculosis and typhoid.¹⁴ Use during antenatal period has been shown to worsen pregnancy and neonatal outcomes.

Assessment

Betel quid addiction can be measured by the Betel Quid Dependence Scale, which has been developed in Taiwan¹⁶ and tested in Guam.¹⁷ This scale includes three domains: physical and psychological urgent need (7 items), increasing dose (5 items) and maladaptive use (4 items). Dependence is noted to increase with increasing duration and frequency of use, and is greater in less-educated persons.

Recommendations

All diabetes care professionals should be aware of the addictive and harmful effects of betel quid chewing. All stakeholders in diabetology should clearly state that betel quid chewing is not recommended in children, adolescents and adults, including persons at risk of diabetes or living with diabetes. Motivation to prevent, limit and manage betel quid chewing should be included as an integral part of routine diabetes care.
Betel quid chewers must be screened for precancerous lesions, cancer and metabolic dysfunction, and encouraged to quit chewing. Non pharmacological measures that can be used to treat betel quid dependence include brief intervention, cognitive behavioral therapy, and motivational interviewing. Healthy eating habits and physical activity must be encouraged in betel quid chewers. Pharmacological measures for betel quid dependence are similar to those used for nicotine dependence containing tobacco. Referral to a mental health professional should be considered if betel quid chewing is not amenable to simple advice and brief intervention and more intensive intervention is needed.
Social and religious leaders must be involved in social marketing about the harmful effects of betel quid chewing, Discussion and research on betel quid chewing should be encouraged in the context of diabetes care in South Asia.

References

1. Boucher BJ, Mannan N. Metabolic effects of the consumption of Areca catechu. Addict Biol. 2002; 7: 103-110.
2. Garg A, Chaturvedi P, Gupta PC.A review of the systemic adverse effects of areca nut or betel nut. Indian J Med Paediatr Oncol 2014; 35: 3-9.
3. Bhat SJ, Blank MD, Balster RL, Nichter M, Nichter M. Areca nut dependence among chewers in a South Indian community who do not also use tobacco. Addiction. 2010; 105: 1303-10.
4. Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, et al. Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer. 2000; 86: 128-31.
5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2004; 85: 1-334.
6. Boucher BJ, Ewen SW, Stowers JM. Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Diabetologia. 1994; 37: 49-55.
7. Tsai AC, Lee SH. Determinants of new-onset diabetes in older adults - Results of a national cohort study. Clin Nutr. 2015; 34: 937-42.
8. Mannan N, Boucher BJ, Evans SJ. 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. Br J Nutr. 2000; 83: 267-75.
9. Wu F, Parvez F, Islam T, Ahmed A, Rakibuz-Zaman M, Hasan R, et al. Betel quid use and mortality in Bangladesh: a cohort study. Bull World Health Organ. 2015; 93: 684-692.
10. Yamada T, Hara K, Kadowaki T. Chewing betel quid and the risk of metabolic disease, cardiovascular disease, and all-cause mortality: a meta-analysis. PLoS One. 2013; 8:e70679. doi: 10.1371/journal.pone.0070679.
11. Allen SE, Singh S, Robertson WG. The increased risk of urinary stone disease in betel quid chewers. Urol Res. 2006; 34: 239-43.
12. Chou CY, Cheng SY, Liu JH, Cheng WC, Kang IM, Tseng YH, et al. Association between betel-nut chewing and chronic kidney disease in men. Public Health Nutr. 2009; 12: 723-7.
13. Ogunkolade WB, Boucher BJ, Bustin SA, Burrin JM, Noonan K, et al. Vitamin D metabolism in peripheral blood mononuclear cells is influenced by chewing "betel nut" (Areca catechu) and vitamin D status. J Clin Endocrinol Metab 2006; 91: 2612-7.
14. Singh PN, Natto Z, Yel D, Job J, Knutsen S. Betel quid use in relation to infectious disease outcomes in Cambodia. Int J Infect Dis. 2012; 16: e262-7.
15. García-Algar O, Vall O, Alameda F. Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes. Arch Dis Child Fetal Neonatal Ed. 2005; 90: F276-F277.
16. Lee CY, Chang CS, Shieh TY, Chang YY. Development and validation of a self-rating scale for betel quid chewers based on a male-prisoner population in Taiwan: the Betel Quid Dependence Scale. Drug Alcohol Depend. 2012b; 121: 18-22.
17. Herzog TA, Murphy KL, Little MA, Suguitan GS, Pokhrel P, Kawamoto CT. The Betel Quid Dependence Scale: replication and extension in a Guamanian sample. Drug Alcohol Depend. 2014; 138: 154-60.