Zinc and Cardio-Metabolic Health in Type 2 Diabetes Mellitus

Abstract

The essentiality of zinc in human nutrition was reported in the 1960s with the identification of young males who had short stature and exhibited hypogonadism. The root cause of the condition was traced back to the consumption of large quantities of dietary phytate, and the practice of geophagia, which was noted often among children in rural or pre-industrial societies. Both of these factors were thought to be responsible for inhibiting zinc absorption and ultimately lead to the diagnosis of zinc deficiency. We now recognize a plethora of symptoms associated with zinc deficiency that include high rates of infections, diverse forms of skin lesions, and impaired wound healing. These wide ranging symptoms point to the involvement of zinc in diverse cellular activities [1,2]. Other evidence implicates zinc in the etiologies of chronic diseases, particularly risk factors that are associated with cardio-vascular disease (CVD) and Type 2 diabetes mellitus (DM) In a recent evaluation of randomized controlled clinical trials that were aimed at determining the effect of zinc supplementation on glycaemic control, we showed a small reduction in fasting glucose concentrations after zinc supplementation. In secondary analyses of participants with chronic metabolic diseases (Types 1 and 2 DM, metabolic syndrome, obesity), zinc supplementation resulted in a greater reduction in plasma glucose concentrations compared to the effect that was observed in healthy participants. These observations are supported further by other reports, mainly of cross-sectional surveys, which suggest that improved zinc status affects favorably the cardiometabolic profile in people with DM [5]. The potential mechanisms that are responsible for the observed effects on glycaemic control may be mediated through the association of zinc with insulin. Under physiological conditions, zinc is abundant throughout the pancreas, but is particularly concentrated in the secretary vesicles of the beta-cells where it forms an integral component of the insulin crystalline structure [6] serving to confer stability to the insulin granule [7]. Zinc transporter 8 (ZnT8) belongs to the CDF/ ZnT (SLC30) family of zinc transporters, and is abundantly expressed in the pancreas. ZnT8 co-localizes with insulin in pancreatic islets and appears to be involved in zinc accumulation and regulation of insulin secretion in beta-cells [8]. Recent evidence suggests that single nucleotide polymorphisms in ZnT8 are associated with impaired proinsulin conversion [9] and increased risk of developing type 2 DM [10,11] .