title: Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish.
abstract: OBJECTIVE
  SLC30A8 encodes a zinc transporter in the beta cell; individuals with a common missense variant (rs13266634; R325W) in SLC30A8 demonstrate a lower early insulin response to glucose and an increased risk of type 2 diabetes. We hypothesised that zinc supplementation may improve insulin secretion in a genotype-dependent manner.
  
  
  METHODS
  We evaluated the early insulin response to glucose (using frequently sampled intravenous glucose tolerance testing) by R325W genotype before and after 14 days of supplementation with oral zinc acetate (50 mg elemental zinc) twice daily in healthy non-diabetic Amish individuals (N = 55).
  
  
  RESULTS
  Individuals with RW/WW genotypes (n = 32) had the lowest insulin response to glucose at 5 and 10 min at baseline (vs RR homozygotes [n = 23]). After zinc supplementation, the RW/WW group experienced 15% and 14% increases in the insulin response to glucose at 5 and 10 min, respectively (p ≤ 0.04), and, compared with RR homozygotes, experienced a 26% (p = 0.04) increase in insulin at 5 min. We observed reciprocal decreases in proinsulin:insulin in the RW/WW (p = 0.002) vs RR group (p = 0.048), suggesting a genotype-specific improvement in insulin processing.
  
  
  CONCLUSIONS
  Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on SLC30A8 variation.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00981448.
authors.affiliation: Division of General Internal Medicine, Johns Hopkins University School of Medicine, 2024 E. Monument Street, Suite 2-600, Baltimore, MD, 21287, USA, maruthur@jhmi.edu.
authors.forename: Nisa M
authors.initials: NM
authors.lastname: Maruthur
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Clark
authors.forename: Mao
authors.initials: M
authors.lastname: Fu
authors.forename: W H
authors.initials: WH
authors.lastname: Linda Kao
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D000328:Adult; D061365:Amish; D019540:Area Under Curve; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics; D019587:Dietary Supplements; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D019345:Zinc Acetate / Q000008:administration & dosage*; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D011384:Proinsulin; D019345:Zinc Acetate