R01DK136529
Project Grant
Overview
Grant Description
Clinical and Nutrigenetic Assessment of Zinc in Patients with Prediabetes - Project Summary
Type 2 diabetes (T2D) is a major cause of morbidity and mortality worldwide, leads to several debilitating chronic conditions including kidney failure, retinopathy, neuropathy, and cardiovascular disease, and results in a substantial burden to the United States healthcare system.
In addition to those with T2D, approximately 90 million Americans have prediabetes, a condition that is associated with several similar health risks and greatly increases the probability of developing T2D in the future.
Given the significant clinical consequences and associated economic impact, there is a major unmet medical need to design new strategies that slow or prevent the progression of prediabetes to T2D.
Currently, no medications are FDA-approved for the treatment of prediabetes; thus, those with this disorder are mainly limited to behavioral lifestyle changes (e.g. increased exercise, weight loss, and diet modification).
Recent investigations, mostly conducted in T2D patients, show that dietary supplementation with zinc confers favorable metabolic effects including reduction in fasting glucose and hemoglobin A1C (HGBA1C).
Indeed, zinc is known to be critical in the biosynthesis, processing, and secretion of insulin in addition to improving insulin sensitivity in peripheral tissues.
Furthermore, recent genomic studies have convincingly shown that variants in genes responsible for islet zinc transport (i.e. SLC30A8) are amongst the strongest genetic determinants of T2D risk.
Given these data, the primary objectives of this application are to 1) assess the utility of zinc supplementation in individuals with prediabetes to improve glycemic indices and insulin action and 2) better characterize the impact of genetic variation in SLC30A8 on glucose control in response to zinc treatment.
To accomplish these objectives, we will conduct a prospective, double-blind placebo-controlled trial of 200 prediabetic subjects that evaluates the effect of zinc supplementation (25 mg/day for 12 months) on HGBA1C, fasting plasma glucose, 2h oral glucose tolerance test measures, and lipid levels at 0, 6, and 12 months.
We will also perform a prospective genotype-directed callback study based on SLC30A8 genotype to assess the effect of genetic variation in this gene on glycemic control in relation to zinc supplementation.
Measures of insulin action including processing (i.e. proinsulin:insulin ratio), clearance (i.e. C-peptide:insulin ratio), and resistance (i.e. Matsuda index) will be evaluated pre- vs. post-zinc supplementation as well as by SLC30A8 genotype.
Discovering new, scalable, and inexpensive strategies that help improve glycemic control with little to no side effects in subjects with prediabetes would ultimately help in reducing chronic complications associated with T2D and lower related healthcare costs.
In addition, we anticipate that the studies outlined in this application will set the stage for more effective genotype-directed approaches in prediabetics and provide justification for future mechanistic studies and larger clinical trials of SLC30A8 genotype-directed treatment and possibly prevention of T2D.
Type 2 diabetes (T2D) is a major cause of morbidity and mortality worldwide, leads to several debilitating chronic conditions including kidney failure, retinopathy, neuropathy, and cardiovascular disease, and results in a substantial burden to the United States healthcare system.
In addition to those with T2D, approximately 90 million Americans have prediabetes, a condition that is associated with several similar health risks and greatly increases the probability of developing T2D in the future.
Given the significant clinical consequences and associated economic impact, there is a major unmet medical need to design new strategies that slow or prevent the progression of prediabetes to T2D.
Currently, no medications are FDA-approved for the treatment of prediabetes; thus, those with this disorder are mainly limited to behavioral lifestyle changes (e.g. increased exercise, weight loss, and diet modification).
Recent investigations, mostly conducted in T2D patients, show that dietary supplementation with zinc confers favorable metabolic effects including reduction in fasting glucose and hemoglobin A1C (HGBA1C).
Indeed, zinc is known to be critical in the biosynthesis, processing, and secretion of insulin in addition to improving insulin sensitivity in peripheral tissues.
Furthermore, recent genomic studies have convincingly shown that variants in genes responsible for islet zinc transport (i.e. SLC30A8) are amongst the strongest genetic determinants of T2D risk.
Given these data, the primary objectives of this application are to 1) assess the utility of zinc supplementation in individuals with prediabetes to improve glycemic indices and insulin action and 2) better characterize the impact of genetic variation in SLC30A8 on glucose control in response to zinc treatment.
To accomplish these objectives, we will conduct a prospective, double-blind placebo-controlled trial of 200 prediabetic subjects that evaluates the effect of zinc supplementation (25 mg/day for 12 months) on HGBA1C, fasting plasma glucose, 2h oral glucose tolerance test measures, and lipid levels at 0, 6, and 12 months.
We will also perform a prospective genotype-directed callback study based on SLC30A8 genotype to assess the effect of genetic variation in this gene on glycemic control in relation to zinc supplementation.
Measures of insulin action including processing (i.e. proinsulin:insulin ratio), clearance (i.e. C-peptide:insulin ratio), and resistance (i.e. Matsuda index) will be evaluated pre- vs. post-zinc supplementation as well as by SLC30A8 genotype.
Discovering new, scalable, and inexpensive strategies that help improve glycemic control with little to no side effects in subjects with prediabetes would ultimately help in reducing chronic complications associated with T2D and lower related healthcare costs.
In addition, we anticipate that the studies outlined in this application will set the stage for more effective genotype-directed approaches in prediabetics and provide justification for future mechanistic studies and larger clinical trials of SLC30A8 genotype-directed treatment and possibly prevention of T2D.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding Agency
Place of Performance
Baltimore,
Maryland
21201
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 683% from $387,355 to $3,032,502.
University Of Maryland, Baltimore was awarded
Zinc Nutrigenetics in Prediabetes: Clinical Assessment
Project Grant R01DK136529
worth $3,032,502
from the National Institute of Allergy and Infectious Diseases in August 2023 with work to be completed primarily in Baltimore Maryland United States.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research.
The Project Grant was awarded through grant opportunity Research Project Grant (Parent R01 Clinical Trial Required).
Status
(Ongoing)
Last Modified 6/5/26
Period of Performance
8/15/23
Start Date
5/31/28
End Date
Funding Split
$3.0M
Federal Obligation
$0.0
Non-Federal Obligation
$3.0M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01DK136529
Additional Detail
Award ID FAIN
R01DK136529
SAI Number
R01DK136529-916976138
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NK00 NIH National Institute of Diabetes and Digestive and Kidney Diseases
Funding Office
75NA00 NIH OFFICE OF THE DIRECTOR
Awardee UEI
Z9CRZKD42ZT1
Awardee CAGE
1B0S2
Performance District
MD-07
Senators
Benjamin Cardin
Chris Van Hollen
Chris Van Hollen
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Health and Human Services (075-0884) | Health research and training | Grants, subsidies, and contributions (41.0) | $387,355 | 50% |
| Office of the Director, National Institutes of Health, Health and Human Services (075-0846) | Health research and training | Grants, subsidies, and contributions (41.0) | $383,353 | 50% |
Modified: 6/5/26