Pharmacokinetics of zinc in pre-diabetes: a pilot study

Abstract

Background: 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 investigate the pharmacokinetic parameters of Zinc in pre-diabetes using the oral Zinc tolerance test. Methods: The present study was conducted as a pharmacokinetic sub-study of a randomized controlled trial evaluating the effects of Zinc supplementation in pre-diabetes. Initially a baseline blood sample was taken (0hrs) after 10hours of overnight fasting. The Zinc 20mg capsule was given to the patient to be taken orally after obtaining this baseline blood sample (0hrs). Subsequent blood samples were taken at 30min, 1h, 2h, 3h and 6h. A 24 hour sample was taken in the morning of the following day. Subjects were given standard meals during the period of the study. Serum Zinc was analyzed by colorimetric method. Pharmacokinetic parameters were calculated using the non-compartment extra-vascular model applied for the Zinc plasma disposition curves. Results: Sample size was 10, of which four patients were males. Mean age (±SD) was 52.6±9.6years. The serum Zinc concentration of all study participants with pre-diabetes prior to the commencement of Zinc supplementation in the clinical trial were below the normal range. The mean serum Zinc concentration (±SD) at baseline (0hours) was 10.63±3.0μmol/l, which was higher than the mean pre-supplementation Zinc concentration (9.06±1.93μmol/l) (p=0.10). The maximal concentration of Zinc (±SD) achieved in the blood (Cmax) was 23.56±4.46μmol/l and Tmax was 2hours. Subsequently the Zinc concentration gradually decreased, however at 24hours an increase in the mean Zinc concentration was observed. The elimination half life (T½) was 4.91hours. Conclusion: Our results show the presence of hypozincaemia in those with pre-diabetes, which was improved with Zinc supplementation. Zinc absorption was normal in the study population, however elimination half life was prolonged. Furthermore, there is possible impairment in entero-hepatic re-circulation observed in this population with pre-diabetes.