Clinical trial NCT05000762: Zinc Supplementation Improves Cardiovascular Morbidity in Patients With Diabetes Mellitus
Official title: Zinc Supplementation Improves Cardiovascular Morbidity in Patients With Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Diabetes Mellitus, Type 2
Cardiovascular Diseases
Keywords: Zinc dietary supplement
diabetes mellitus
cardiovascular reactivity
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: QPathology
First posted: 2021-08-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Pulse wave velocity
timeFrame: 4 months
measure: Cerebrovascular reactivity
timeFrame: 4 months
measure: Blood pressure response to exercise
timeFrame: 4 months
measure: Platelet aggregation
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
Study officials:
affiliation: Wayne State University
name: Warren Lockette, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.