Study of oral zinc supplementation effect on the superoxide dismutase gene expression and enzyme activity, and oxidative stress index in overweight type 2 diabetic patients.

Type 2 diabetes mellitus is one of the major health concerns around the globe due to its widespread prevalence. Chronic hyperglycemia, followed by glucose autoxidation and lipids peroxidation can increase oxidative and nitrosative oxidations, which eventually result in increase of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (NOS). Zinc is one of the essential micronutrients, homeostasis of which changes in diabetes mellitus disease. Different studies indicate the low serum level and high urinary excretion in diabetic patients. Recent studies have shown that Zinc has an anti-oxidative characteristic. This element can improve the anti-oxidative status and decrease the oxidative stress inducers of lipids, proteins. Also, it can have a pivotal role in the synthesis, secretion, stability, and signal transduction of insulin. In clinical and epidemiological research studies, the nutritive status of Zinc has been suggested as a critical factor for deterioration of the disease. So, regarding the increasing incidence of the diabetes mellitus and the nutritive significance of Zinc, it seems essential to investigate the effect of the Zinc oral supplementation in aspect of anti-oxidant therapy on alteration of oxidative/nitrosative stress index. The aim of our study is to determine the eight-week oral supplementation effect on superoxide dismutase gene expression and enzyme activity, stress-oxidative index, and insulin resistance in overweight type 2 diabetic patients.

This research is a double blind clinical trial, phase III, on 70 type 2 diabetic patients with overweight, who will refer to Diabetes and Metabolic Diseases Clinic of Endocrinology and Metabolism Research Institute. All participants write informed consent prior to study enrollment. Participants will be randomly divided to two groups, intervention and control. The intervention group will take the gluconate Zinc capsule (25 mg) twice daily for 8 weeks. In same condition, the control group will consume placebo capsule. Once a week, taking supplements will be checked via telephone.

This study is going to be carried out as a matched, randomized double-blind, placebo controlled clinical trial among qualified participants with type 2 diabetes, who referred to Diabetes and Metabolic Diseases Clinic of Endocrinology and Metabolism Research Institute. Participants will be randomly assigned to two groups: zinc gluconate (25mg, twice daily) group (n=35), and placebo group (n=35), who will take the supplement for 8 weeks. 7 mL blood samples will be taken from each participant after 12 hour fasting condition. In other words, we will allocate 2ml blood in EDTA tube for gene analysis and HbA1c assay, and 5ml in plain tube for biochemistry assays, such as serum levels of zinc, superoxidedismutase activity, nitrotyrosine, malondialdehyde, total antioxidant capacity, total oxidant status, insulin, fasting blood sugar, lipid profile. Biochemical data will be evaluated and reported before and after the 8 weeks of supplementation for all patients at the end of study. In this study, all the participants, the primary researcher, health care providers, sample collectors, and those who prepare manuscript draft were blinded.

Inclusion criteria: male/female with age 40-65, type 2 diabetes, BMI = 25-30, Hb A1c ≥7, who comparing to control group use lowering blood glucose drugs. Exclusion criteria: cigarette smoking, any history of cancer, thyroid or gastrointestinal or renal disorders, as well as taking diuretics, antibiotics, and vitamin/mineral supplements containing zinc less than two months before the start of the study.

The case groups will take 25 mg the gluconate Zinc capsule (twice daily), and the control group will take Avicel placebo capsule twice daily. Patients will take these capsules for 8 weeks.

Superoxide dismutase gene expression superoxide dismutase activity Zinc Fasting Blood Sugar Hemoglobin a1c Nitrotyrosine Total antioxidant capacity Total oxidant capacity Malondialdehyde Insulin Body mass index

Simple-block randomization

In this study, all the participants, the primary researcher, health care providers, sample collectors, and those who prepare manuscript draft were blinded.

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