title: Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families.
abstract: OBJECTIVE
  While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D.
  
  
  METHODS
  Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes.
  
  
  RESULTS
  Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment--insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals.
  
  
  CONCLUSIONS
  Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D.
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Manju
authors.initials: M
authors.lastname: Mamtani
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Juan
authors.initials: J
authors.lastname: Peralta
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Marcio
authors.initials: M
authors.lastname: Almeida
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Goring
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States of America.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams-Blangero
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008598:Menstruation; D017058:Mexican Americans; D013781:Texas
chemical_list: D015815:Cell Adhesion Molecules