Zinc Supplementation Improves Cardiovascular Morbidity in Patients With Diabetes Mellitus

NCT ID: NCT05000762

Last Updated: 2023-12-12

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2025-12-31

Brief Summary

Oral zinc supplementation in patients with diabetes mellitus can improve glycemic control. However, there is reluctance to recommend zinc supplements to these patients because there is no evidence that the zinc-dependent improvement in glycemic control offers protections from the cardiovascular morbidities associated with diabetes mellitus, especially myocardial infarction and thrombotic stroke. The investigators are conducting a randomized, double blind, cross over study to test the hypothesis that oral zinc supplementation will block the enhanced cardiovascular, cerebrovascular, and platelet reactivity that lead to myocardial infarction and stroke in research participants with diabetes mellitus.

Detailed Description

Diabetes mellitus induces adverse changes in the systemic blood vessels, the cerebral vasculature, and platelets that can culminate in myocardial infarction and thrombotic stroke. Also, when compared to patients whose diabetes mellitus is well controlled, poor glucose maintenance in men and women with diabetes mellitus undeniably confers a much greater risk of myocardial infarction and stroke. For these reasons, it is important to maintain euglycemia in patients with diabetes mellitus. Several studies have shown supplemention with oral zinc improves glycemic control in patients with diabetes mellitus. Zinc supplementation has been associated with an absolute fall in glycosylated hemoglobin (HgbA1c), a measurement of metabolic control, by 0.5 percentage points. It is unknown whether this dietary supplement improves the exaggerated systemic and cerebrovascular and platelet responsiveness that are responsible for the increased prevalence of myocardial infarction and stroke in patients with diabetes mellitus. The investigators postulate that zinc dietary supplementation, when compared to placebo, will significantly reduce the increased cardiovascular reactivity and thrombogenesis associated with myocardial infarction or stroke in men and women with diabetes mellitus. The investigators will conduct a randomized, double-blinded, cross over study in volunteers with diabetes mellitus in which the participants receive either four months of placebo or oral zinc gluconate (30 mg zinc gluconate). Subjects will have validated, non-invasive, non-pharmacologic assessments of both their systemic and cerebrovascular reactivity and platelet responsiveness. The investigators anticipate that zinc supplementation will enhance flow mediated endothelium-dependent vasodilation in the peripheral vasculature in patients with diabetes mellitus, and also, reduces cardiovascular responses to stress. It is expected that zinc supplementation will blunt the magnitude of blood pressure increases induced by exercise in the research subjects. Also, the investigators expect to show that zinc supplementation, when compared to placebo, reduces pulse wave velocity, a measure of vascular stiffness, in the research subjects with diabetes mellitus. The investigators will show that zinc supplementation, when compared to placebo, improves cerebral blood flow in patients with diabetes mellitus. The investigators will assess cerebrovascular reactivity by measuring the sensitivity of intracerebral blood vessels to increasing concentrations of pCO2, a maneuver which selectively relaxes the cerebral vasculature and increases cerebral blood flow. Finally, the investigators anticipate that zinc supplementation will reduce platelet aggregation.

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Keywords

Zinc dietary supplement; diabetes mellitus; cardiovascular reactivity

Study Design

• Observational Model Type: CASE_CROSSOVER
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with diabetes mellitus

Patients with type 2 diabetes mellitus

Zinc

Intervention Type: DIETARY_SUPPLEMENT

Zinc gluconate 30 mg/day orally

Interventions

Zinc

Zinc gluconate 30 mg/day orally

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Only patients with stable type 2 diabetes mellitus or pre-diabetes (HgbA1c between 6% - 9%) and who are otherwise healthy

Exclusion Criteria

• Pregnant women
• Anyone unable to understand or give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

QPathology

UNKNOWN

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Warren Lockette, M.D.

Professor of Medicine and Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Warren Lockette, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

Wayne State University School of Medicine

Detroit, Michigan, United States

Countries

United States

References

Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012 Apr 19;4(1):13. doi: 10.1186/1758-5996-4-13.

Reference Type: BACKGROUND

PMID: 22515411 (View on PubMed)

Other Identifiers

IRB-20-10-2833

Identifier Type: -

Identifier Source: org_study_id