Nutrigenomics of Zinc Supplementation in Insulin Secretion and Diabetes

As diabetes increases at an alarming rate, strategies for prevention of this disease must be
developed. For a given individual, there are both biologic (e.g., genetic) and
environmental (e.g., lifestyle) factors that comprise her individual risk of diabetes.
Researchers can take advantage the accumulating knowledge of these individual factors to
design individualized strategies for diabetes risk assessment and prevention. For example,
a mutation in a particular gene, SLC30A8, which encodes a zinc transporter, has been shown
to increase the risk of diabetes probably through impairment of insulin secretion. In the
proposed research project, the investigators aim to conduct a pilot study to see the effect
of zinc supplementation on insulin secretion in people with and without this genetic
mutation to see if zinc can improve insulin secretion in those with the mutation. The
results from this study will help the investigators to plan a larger, more definitive study
to determine if zinc supplementation can be used to prevent or treat diabetes in those with
this mutation in SLC30A8.

Inclusion Criteria:

- aged 21-70 years

- Amish decent

- genotyping of rs13266634 of SLC30A8 gene

- previously consented to contact for future studies and future use of DNA

Exclusion Criteria:

- Subject is a first-degree relative of another subject with the same SLC30A8 genotype

- diabetes mellitus (by history, treatment or random BG>200 mg;dl)

- gastrointestinal disease causing nausea, vomiting, or diarrhea including inflammatory
bowel disease by history.

- rheumatoid arthritis by history

- albumin < 3.5 g/dL

- hemochromatosis by history

- hematocrit <34%

- liver disease by history

- alanine aminotransferase or aspartate aminotransferase greater than 2.5 times normal

- renal failure by history

- estimated glomerular filtration rate < 60 mL/min by MDRD equation

- use of thiazide diuretic and unwilling to discontinue if deemed safe in the opinion
of the treating physician and study physician for 1 week prior to protocol initiation

- use of systemic corticosteroid and unwilling to discontinue if deemed safe in the
opinion of the treating physician and study physician for 1 week prior to protocol
initiation

- use of highly-active antiretroviral medications

- use of antipsychotic medications

- use of quinolone antibiotics

- use of tetracycline antibiotic and unwilling to discontinue if deemed safe in the
opinion of the treating physician and study physician for 1 week prior to protocol
initiation

- use of chelation therapy in the past month

- unwilling to withdraw from supplements for 1 week prior to the study and throughout
study

- abnormal thyroid stimulating hormone (TSH) level

- serious disease precluding participation

- reported pregnancy or positive urine hCG test

- cancer diagnosis in past 2 years

- breastfeeding

- use of denture adhesive