Betel nut chewing is associated with increased production of reactive oxygen species and inflammatory mediators (1), which could potentially cause kidney damage (2). This study investigated whether betel nut chewing could increase urinary albumin excretion rate (UAER) in 572 Taiwanese men (aged ≥45 years) with type 2 diabetes. Among them, 65 were chewers ≥5 years and 507 were nonchewers. Urinary albumin and creatinine concentrations, fasting plasma glucose and serum total cholesterol, triglycerides, and creatinine were measured as described elsewhere (3). Urinary albumin-to-creatinine ratio (ACR) ≥30.0 μg/mg was defined as albuminuria. Creatinine clearance (Ccr) was calculated from the Cockcroft-Gault formula (3). Statistical analyses were performed considering confounders including age, diabetic duration, smoking, BMI, blood pressure, metabolic control, and Ccr.
Results showed that chewers were significantly younger (56.4 ± 8.6 vs. 65.0 ± 9.5 years), had higher prevalence of smoking (89.2 vs. 62.2%), higher BMI (25.7 ± 3.5 vs. 24.8 ± 3.2 kg/m2), poorer glycemic control (176.0 ± 71.9 vs. 158.8 ± 61.6 mg/dl), higher ln(ACR) (4.0 ± 1.7 vs. 3.5 ± 1.5 μg/mg), and higher prevalence of albuminuria (61.5 vs. 47.5%). However, diabetic duration, systolic and diastolic blood pressures, cholesterol, triglycerides, and Ccr were not significantly different. In multiple linear regression, the adjusted regression coefficient for ln(ACR) associated with betel nut chewing was 0.427 (P < 0.05). The multivariate-adjusted odds ratio for albuminuria in chewers versus nonchewers was 2.024 (95% CI 1.129–3.630). In stepwise models of multiple linear and logistic regression, betel nut chewing was selected as an independent variable associated with elevated ln(ACR) and albuminuria, respectively. Therefore, the kidney-damaging effect of betel nut chewing was consistent and independent of confounders.
Constituents of areca nut and Piper betle flower may exert sympathomimetic effects (4), which might elevate blood pressure leading to increased UAER. However, because the effect was independent of blood pressure, other mechanisms should have been in play. Reactive oxygen species and N-nitroso compounds can be formed in the oral cavity during betel nut chewing, and in vitro studies also demonstrated that betel nut components increased the release of inflammatory mediators including prostanoids, interleukin-6, and tumor necrosis factor-α (1). Increased oxidative stress and inflammation are also associated with glomerular damage and increased UAER (2). Therefore, the inflammatory mediators produced with betel nut chewing could be responsible.
In conclusions, betel nut chewing is independently associated with increased UAER and albuminuria in Taiwanese type 2 diabetic male patients in this cross-sectional observation. However, future prospective longitudinal studies are warranted for confirmation.