Zinc and Diabetes in Patients With Thalassemia: a Pilot Study

Study Overview
=================
Brief Summary
-----------------
The primary aim of this study is to measure zinc status and related proteins in patients with Thalassemia who have or do not have diabetes. The secondary aim will be to explore the effect of zinc supplementation on glucose metabolism in patients with thalassemia.

Detailed Description
-----------------
Patients with Thalassemia major (Thal) require frequent blood transfusions and are at risk for iron overload. High tissue iron increases the risk of various endocrinopathies, including diabetes, as well as cardiovascular disease, and infections due to the formation of free radicals. This systemic condition of oxidative stress elicits an antioxidant response to reduce tissue damage. Zinc is an important component of that response because it can compete with iron for multiple cellular binding sites and, therefore, reduce the redox-cycling of iron and minimize iron-mediated oxidation of lipids, proteins, and DNA. In Thal patients with chronic hepatic iron overload, tissue zinc redistribution is likely to be persistent. This could create an unbalanced tissue zinc distribution with excessive amounts in the liver and deficient levels in other tissues altering zinc-dependent functions, such as growth, skeletal development, immunity, and glucose regulation. There is a rich body of literature focused on the 'diabetogenic effects' of altered zinc status which will be reviewed herein. Our group has recently shown that supplementation with 25 mg/d of zinc can improve bone density in patients with Thal. This provides evidence for a functional zinc deficiency, which may also affect other whole body zinc functions, such as insulin secretion and glucose homeostasis. Our hypothesis is that hepatic iron overload induces a sub-clinical inflammatory response that alters the expression of MT and zinc-transport proteins leading to hepatic zinc sequestration, and an associated zinc-depletion in other tissues. Marginal zinc depletion in turn leads to increased oxidative stress, cellular apoptosis and altered glucose homeostasis and insulin secretion. This proposal will focus on cross-sectional differences in markers of glucose homeostasis and zinc status in diabetic and non-diabetic Thal patients, combined with a short- term zinc supplementation to explore the effect on glucose and insulin homeostasis.

Official Title
-----------------
Zinc and Diabetes in Patients With Thalassemia: a Pilot Study

Conditions
-----------------
Thalassemia

Intervention / Treatment
-----------------
* Dietary Supplement: Zinc Supplementation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients diagnosed with transfusion dependent thalassemia > 12 years of age Exclusion Criteria (for both cross-sectional and interventional studies) patients who are pregnant patients who are on growth hormone therapy Exclusion criteria (for intervention study only) patients who currently have diabetes (therefore cannot have an oral glucose tolerance test)

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zinc Supplementation<br>25 mg elemental Zinc as Zn sulfate in capsule form taken daily for 3 months | Dietary Supplement: Zinc Supplementation<br>* 25 mg elemental zinc taken as zinc sulfate in capsule form taken daily for 3 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral glucose Tolerance Test | Effect of 3 months of zinc supplementation on oral glucose tolerance test results | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fructosamine | Determine the effect of 3 months of zinc supplementation on fructosamine levels | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Thalassemia, Zinc, Iron-Overload, Diabetes