title: Caffeine Consumption Contributes to Skin Intrinsic Fluorescence in Type 1 Diabetes.
abstract: BACKGROUND
  A variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine.
  
  
  METHODS
  SIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and SIF14 (456-nm LED). Food frequency questionnaires were used to estimate mean caffeine intake. To establish replication, we examined a second type 1 diabetes cohort.
  
  
  RESULTS
  Higher caffeine intake was significantly associated with higher SIF1(LED 375 nm[0.6, 0.2]) (P=2×10(-32)) and SIF14L(ED 456 nm[0.4, 0.8]) (P=7×10(-31)) and accounted for 4% of the variance in each after adjusting for covariates. When analyzed together, caffeine intake and rs1495741 both remained highly significantly associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]). Mean caffeinated coffee intake was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) (P=9×10(-12)) and SIF14(LED 456 nm[0.4, 0.8]) (P=4×10(-12)), but no association was observed for decaffeinated coffee intake. Finally, caffeine was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]) (P<0.0001) in the replication cohort.
  
  
  CONCLUSIONS
  Caffeine contributes to SIF. The effect of rs1495741 on SIF appears to be partially independent of caffeine consumption. Because SIF and coffee intake are each associated with cardiovascular disease, our findings suggest that accounting for coffee and/or caffeine intake may improve risk prediction models for SIF and cardiovascular disease in individuals with diabetes.
authors.affiliation: 1 Program in Genetics and Genome Biology, Hospital for Sick Children , Toronto, Ontario, Canada .
authors.forename: Karen M
authors.initials: KM
authors.lastname: Eny
authors.affiliation: 2 Department of Epidemiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
authors.affiliation: 2 Department of Epidemiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Rachel Grace
authors.initials: RG
authors.lastname: Miller
authors.affiliation: 3 VeraLight, Inc. , Albuquerque, New Mexico.
authors.forename: John
authors.initials: J
authors.lastname: Maynard
authors.affiliation: 4 Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada .
authors.forename: Denis M
authors.initials: DM
authors.lastname: Grant
authors.affiliation: 2 Department of Epidemiology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: 5 The Biostatistics Center, The George Washington University , Rockville, Maryland.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cleary
authors.affiliation: 5 The Biostatistics Center, The George Washington University , Rockville, Maryland.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Braffett
authors.affiliation: 1 Program in Genetics and Genome Biology, Hospital for Sick Children , Toronto, Ontario, Canada .|6 Dalla Lana School of Public Health, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
mesh_terms: D000293:Adolescent; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage*; D003069:Coffee; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D003069:Coffee; D017127:Glycation End Products, Advanced; D002110:Caffeine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human