Zinc Supplementation Improves Cardiovascular Morbidity in Patients With Diabetes Mellitus

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.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Diseases; Diabetes Mellitus, Type 2
• Intervention / Treatment: Dietary supplement: Zinc

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Men and women between the ages of 18 - 75 years who have stable type 2 diabetes or pre-diabetes reflected by a glycosylated heoglobin A1C between 6% - 9%. On no prescription medications other than for diabetes mellitus or nutritional supplements containing zinc

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with diabetes mellitus; Patients with type 2 diabetes mellitus	Dietary supplement: Zinc; Zinc gluconate 30 mg/day orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse wave velocity	Measure changes non-invasively wtihcarotid-femoral pulse wave velocity	4 months
Cerebrovascular reactivity	Measure vasodilation in response to increasing pCO2	4 months
Blood pressure response to exercise	Assess blood pressure response to hand grip exercise	4 months
Platelet aggregation	Measure catecholamine-induced platelet aggregation ex vivo	4 months

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: QPathology
• Investigators: Principal Investigator: Warren Lockette, MD, Wayne State University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: diabetes mellitus; cardiovascular reactivity; Zinc dietary supplement
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: IRB-20-10-2833

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only anonymous, aggregate data will be shared, and only upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No