Abbreviations: AUC, area under the curve; BMI, body mass index; GCP, good clinical practice; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; ITI, industrial technology institute; SD, standard deviation; WHO, world health organization IntroductionZinc is an essential trace element that plays a vital role as a co-factor in enzyme action, cell membrane stabilization, gene expression and cell signaling.1 It is also important in insulin action and carbohydrate metabolism.2 Zinc is involved in the physiology of insulin at several stages; it is found in the insulin secretory granules and is known to participate in the insulin synthesis, stabilization of pro-insulin, insulin secretion, insulin sensitivity, and insulin degradation.3,4 Zinc could also play a role in the pathogenesis of diabetes. Studies have shown that diabetes is accompanied by hypozincemia and hyperzincuria. 5,6 Zinc absorption is also know to be altered in patients with diabetes. 7The altered Zinc absorption and hyperzincuria identified in patients with diabetes is an indication of either the fact that Zinc metabolism is altered as a result of diabetes or the altered Zinc metabolism plays a role in the pathogenesis of diabetes. Homeostasis of Zinc is thought to depend on absorption as well as excretion. Studies have shown that the Zinc ingested by healthy persons are eliminated in the feces (90%) and in urine (2-10%).8 Zinc is primarily absorbed from small intestine, duodenum and ileum. 9 The oral Zinc tolerance test was proved to be an acceptable method to study zinc absorption and excretion in humans.10 Absorption and/or excretion of Zinc may be altered in various pathological states, such as diabetes mellitus. Pre-diabetes is an intermediate state of hyperglycemia with glycaemic parameters above normal but below the threshold for the initiation of treatment for diabetes.11 The pre-diabetic state is characterized by either impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or both. In a meta-analysis evaluating the progression of pre-diabetes to diabetes published in 2007, the annual incidence rate of diabetes was found to be 4%-6% for isolated IGT, for isolated IFG 6%-9% and for both Presently there are no studies examining the pharmacokinetic properties of Zinc in pre-diabetes. Understanding Zinc metabolism in the pre-diabetic state could help to define the role of Zinc in the pathogenesis of diabetes mellitus. Hence the present study aims to investigate the pharmacokinetic parameters of Zinc in pre-diabetes using the oral Zinc tolerance test. MethodsThe present study was conducted as a pharmacokinetic substudy of a randomized controlled trial evaluating the effects of Zinc AbstractBackground: Zinc is an essential trace element that plays a vital role as a co-factor in enzyme action. It is also important in insulin action and carbohydrate metabolism. Understanding Zinc metabolism in the pre-diabetic state could help to define the role of Zinc in the pathogenesis of diabetes mellitus. The present study aims to investi...