Reply

Dear Sir,

We thank Dr Kawada for the interest in our study regarding exposure to heavy metals and smoking with risk of diabetes among occupational workers [1].

Although the study of heavy metals on diabetes development is currently under-researched, there is growing epidemiological evidence linking environmental chemicals, particularly heavy metals, to diabetes. Among heavy metals associated with the risk of diabetes, arsenic has received special attention and increasing prospective evidence is generally consistent with an increased diabetes risk. Dr Kawada stated that there is no clear association between arsenic and risk of type 2 diabetes (T2D) in the systematic review cited in the letter [2]. However, the authors of this review had concluded that the evidence is suggestive but not sufficient for the relationship. Several other toxic metals and essential trace metals have also been linked to T2D, prediabetes and metabolic syndrome as recently reviewed by others [3,4]. A relationship between heavy metal exposure and increased T2D risk is biologically plausible [5–7]. It has been recognized that large longitudinal studies that prospectively investigate the role of multiple metal exposures and their independent and joint effects on T2D are urgently needed to further evaluate heavy metal exposures as risk factors for diabetes [8,9].

We are particularly encouraged that Dr Kawada recognized the need to conduct quantitative evaluation on specific metal and diabetes risk. In our recent study [10], we had performed an exploratory analysis with 464 metal-exposed workers to directly evaluate the dose–response associations between urinary levels of multiple metals and fasting plasma glucose (FPG) and dysglycemia. We found that increased level of nickel and imbalanced levels of zinc were positively associated with elevated FPG and dysglycemia while cobalt was negatively associated with risk of high FPG and dysglycemia. Our preliminary results support the notion that metal exposure may play an important role in the risk T2D in humans.

We fully agree that further studies are needed to examine the relationship between tobacco smoking cessation and the risk of diabetes and prediabetes, and the joint effects between tobacco smoking and heavy metal exposures on the risk of T2D.

Considering that T2D and its complications is a major public health problem worldwide, it is critical to understand the preventable determinants of this disease in order to establish appropriate interventions to assist with prevention efforts. Of the known risk factors for T2D, obesity is considered to play a significant role in the risk of the disease [11]. Body mass index, however, varies widely in patients with T2D indicating that other factors unrelated to obesity are likely implicated in the risk of T2D [12,13]. Recent experimental and epidemiological studies indicate that heavy metal exposure deserves consideration as a risk factor for T2D and this association is biologically plausible. Due to the inconclusive nature of the reported epidemiological association and the widespread exposure to heavy metals, there exists an urgent need for larger, more rigorous epidemiologic studies to investigate the alleged association and to determine the optimal levels of essential metals in reducing the toxic metal impacts on T2D. We are currently conducting a large prospective cohort study with over 45000 participants—The China Metal-exposed Workers Cohort Study (Jinchang Cohort) [14]—and one of the major aims of the study is to investigate the role of multiple heavy metal exposures on the risk of T2D.