Dataset Information

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.

Conclusion

Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D.

SUBMITTER: Kulkarni H

PROVIDER: S-EPMC4805238 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families.

Kulkarni Hemant H Mamtani Manju M Peralta Juan J Almeida Marcio M Dyer Thomas D TD Goring Harald H HH Johnson Matthew P MP Duggirala Ravindranath R Mahaney Michael C MC Olvera Rene L RL Almasy Laura L Glahn David C DC Williams-Blangero Sarah S Curran Joanne E JE Blangero John J

PloS one 20160323 3

<h4>Objective</h4>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.<h4>Methods</h4>Da ...[more]

PMID: 27007680

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Project description:There is growing interest in the hypertriglyceridemic waist (HTGW) phenotype, defined as high waist circumference (?95 cm in males and ?80 cm in females) combined with high serum triglyceride concentration (?2.0 mmol/L in males and ?1.5 mmol/L in females) as a marker of type 2 diabetes (T2D) and cardiovascular disease. However, the prevalence of this phenotype in high-risk populations, its association with T2D, and the genetic or epigenetic influences on HTGW are not well explored. Using data from large, extended families of Mexican Americans (a high-risk minority population in the USA) we aimed to: (1) estimate the prevalence of this phenotype, (2) test its association with T2D and related traits, and (3) dissect out the genetic and epigenetic associations with this phenotype using genome-wide and epigenome-wide studies, respectively.Data for this study was from 850 Mexican American participants (representing 39 families) recruited under the ongoing San Antonio Family Heart Study, 26 % of these individuals had HTGW. This phenotype was significantly heritable (h (2) r?=?0.52, p?=?1.1?×?10(-5)) and independently associated with T2D as well as fasting glucose levels and insulin resistance. We conducted genome-wide association analyses using 759,809 single nucleotide polymorphisms (SNPs) and epigenome-wide association analyses using 457,331 CpG sites. There was no evidence of any SNP associated with HTGW at the genome-wide level but two CpG sites (cg00574958 and cg17058475) in CPT1A and one CpG site (cg06500161) in ABCG1 were significantly associated with HTGW and remained significant after adjusting for the closely related components of metabolic syndrome. CPT1A holds a cardinal position in the metabolism of long-chain fatty acids while ABCG1 plays a role in triglyceride metabolism.Our results reemphasize the value of HTGW as a marker of T2D. This phenotype shows association with DNA methylation within CPT1A and ABCG1, genes involved in fatty acid and triglyceride metabolism. Our results underscore the importance of epigenetics in a clinically informative phenotype.

Project description:BackgroundAlthough obesity rates are high among Latino children, relatively few studies of parental feeding practices have examined Latino families as a separate group. Culturally-based approaches to measurement development can begin to identify parental feeding practices in specific cultural groups. This study used qualitative and quantitative methods to develop and test the Parental Feeding Practices (PFP) Questionnaire for use with Mexican American parents. Items reflected both parent's use of control over child eating and child-centered feeding practices.MethodsIn the qualitative phase of the research, 35 Latino parents participated in focus groups. Items for the PFP were developed from focus group discussions, as well as adapted from existing parent feeding practice measures. Cognitive interviews were conducted with 37 adults to evaluate items. In the quantitative phase, mothers and fathers of 174 Mexican American children ages 8-10 completed the PFP and provided demographic information. Anthropometric measures were obtained on family members.ResultsConfirmatory factor analyses identified four parental feeding practice dimensions: positive involvement in child eating, pressure to eat, use of food to control behavior, and restriction of amount of food. Factorial invariance modeling suggested equivalent factor meaning and item response scaling across mothers and fathers. Mothers and fathers differed somewhat in their use of feeding practices. All four feeding practices were related to child body mass index (BMI) percentiles, for one or both parents. Mothers reporting more positive involvement had children with lower BMI percentiles. Parents using more pressure to eat had children with lower BMI percentiles, while parents using more restriction had children with higher BMI percentiles. Fathers using food to control behavior had children with lower BMI percentiles.ConclusionsResults indicate good initial validity and reliability for the PFP. It can be used to increase understanding of parental feeding practices, children's eating, and obesity among Mexican Americans, a population at high risk of obesity.

Dataset Information

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families.

Objective

Methods

Results

Conclusion

Publications

Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families.

Similar Datasets

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