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Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study.

ABSTRACT: Published data concerning associations between IRS1 variants and type 2 diabetes and related traits have been inconsistent. We examined the relationship between common variants in IRS1, type 2 diabetes, and related traits including insulin resistance, hyperglycemia and DNA damage in the Boston Puerto Rican Health Study.We genotyped six common IRS1 variants in an adult Puerto Rican population (n=1132) and tested for association with risk of type 2 diabetes and related traits.SNPs rs934167 and rs1801123 showed significant association with fasting glucose concentrations (p = 0.005 and p = 0.016, respectively) and rs934167 showed significant association with plasma insulin levels (p = 0.005). Carriers of the rs934167 minor allele had significantly higher HOMA-IR and lower QUICKI (p = 0.001 and p = 0.001, respectively), and a 40% and 58% greater likelihood of being hyperglycaemic or hyperinsulinemic (OR = 1.40 and 1.58; p = 0.013 and 0.002, respectively). However, they exhibited only a marginally significant trend towards having type 2 diabetes (OR=1.27, p = 0.077). Furthermore, carriers of the haplotype C-T of the rs934167 and rs1801123 minor alleles showed consistent patterns of associations after correction for multiple testing. In addition, the G972R (rs1801278) minor allele was significantly associated with higher urinary 8-OHdG concentrations (p = 0.020) and plasma CRP levels (p = 0.035).Our results support IRS1 variants associated with type 2 diabetes risk in adult Puerto Ricans. Moreover, we report the novel finding that IRS1 variant G972R (rs1801278) may contribute to oxidative DNA damage and inflammation.

SUBMITTER: Feng X

PROVIDER: S-EPMC4428925 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study.

Feng Xiang X Tucker Katherine L KL Parnell Laurence D LD Shen Jian J Lee Yu-Chi YC Ordovás José M JM Ling Wen-Hua WH Lai Chao-Qiang CQ

Asia Pacific journal of clinical nutrition 20130101 1

<h4>Objective</h4>Published data concerning associations between IRS1 variants and type 2 diabetes and related traits have been inconsistent. We examined the relationship between common variants in IRS1, type 2 diabetes, and related traits including insulin resistance, hyperglycemia and DNA damage in the Boston Puerto Rican Health Study.<h4>Methods</h4>We genotyped six common IRS1 variants in an adult Puerto Rican population (n=1132) and tested for association with risk of type 2 diabetes and re ...[more]

PMID: 23353623

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Project description:Background and objectivesThe Boston Puerto Rican Health Study (BPRHS) is a longitudinal study following self-identified Puerto Rican older adults living in the Greater Boston area. Studies have shown higher prevalence of hypertension (HTN) and type 2 diabetes (T2D) within this ethnic group compared to age-matched non-Hispanic White adults. In this study, we investigated the associations of HTN and T2D comorbidity on brain structural integrity and cognitive capacity in community-dwelling Puerto Rican adults and compared these measures with older adult participants (non-Hispanic White and Hispanic) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC) databases.MethodsBPRHS participants who underwent brain MRI and cognitive testing were divided into 4 groups based on their HTN and T2D status: HTN-/T2D-, HTN+/T2D-, HTN-/T2D+, and HTN+/T2D+. We assessed microstructural integrity of white matter (WM) pathways using diffusion MRI, brain macrostructural integrity using hippocampal volumes, and brain age using T1-weighted MRI and cognitive test scores. BPRHS results were then compared with results from non-Hispanic White and Hispanic participants from the ADNI and NACC databases.ResultsThe prevalence of HTN was almost 2 times (66.7% vs 38.7%) and of T2D was 5 times (31.8% vs 6.6.%) higher in BPRHS than in ADNI non-Hispanic White participants. Diffusion MRI showed clear deterioration patterns in major WM tracts in the HTN+/T2D+ group and, to a lesser extent, in the HTN+/T2D- group compared to the HTN-/T2D- group. HTN+/T2D+ participants also had the smallest hippocampal volume and larger brain aging deviations. Trends toward lower executive function and global cognitive scores were observed in HTN+/T2D+ relative to HTN-/T2D- individuals. MRI measures and the Mini-Mental State Examination (MMSE) scores from the HTN+/T2D+ BPRHS group resembled those of ADNI White participants with progressive mild cognitive impairment (MCI), while the BPRHS HTN-/T2D- participants resembled participants with stable MCI. The BPRHS was not significantly different from the ADNI + NACC Hispanic cohort on imaging or MMSE measures.DiscussionThe effects of T2D and HTN comorbidity led to greater brain structural disruptions than HTN alone. The high prevalence of HTN and T2D in the Puerto Rican population may be a key factor contributing to health disparities in cognitive impairment in this group compared to non-Hispanic White adults in the same age range.Trial registration informationClinicalTrials.gov identifier: NCT01231958.

Project description:Puerto Ricans living in the United States mainland present multiple disparities in prevalence of chronic diseases, relative to other racial and ethnic groups. Allostatic load (AL), or the cumulative wear and tear of physiological responses to stressors such as major life events, social and environmental burden, has been proposed as a possible mechanism for the inequalities observed in minority groups, but has not been studied in Puerto Ricans. The aim of this study was to determine the association of AL to six chronic diseases (abdominal obesity, hypertension, diabetes, and self-reported cardiovascular disease (CVD), arthritis and cancer) in Puerto Ricans, and to contrast AL to metabolic syndrome (MetS). Participants of the Boston Puerto Rican Health Study (n=1116, ages 45-75 years) underwent a home-based interview, where questionnaires were completed and biological samples collected. A summary definition of AL was constructed using clinically-defined cutoffs and medication use for 10 physiological parameters in different body systems. Logistic regression models were run to determine associations between AL score and disease status, controlling for age, sex, smoking, alcohol use, physical activity, total fat intake and energy intake. Parallel models were also run with MetS score replacing AL. We found that increasing categories of AL score were significantly associated with abdominal obesity, hypertension, diabetes and self-reported cardiovascular disease (CVD) and arthritis, but not with self-reported cancer. The strength of associations of AL with all conditions, except diabetes and cancer, was similar to or larger than those of MetS score. In conclusion, Puerto Rican older adults experienced physiological dysregulation that was associated with increased odds of chronic conditions. AL was more strongly associated with most conditions, compared to MetS, suggesting that this cumulative measure may be a better predictor of disease. These results have prospective research implications for Puerto Ricans and other ethnic groups.

Project description:BackgroundPuerto Rican adults residing in the US mainland experience a high prevalence of metabolic syndrome (MetS). A diet containing healthy protein-rich sources may help control risk factors for MetS.ObjectiveThis study aimed to evaluate 2-year longitudinal associations between intake of various protein-rich foods and changes in the six MetS components.DesignThis is a secondary analysis of a longitudinal cohort study using data from the baseline (2004-2007) and 2-year follow-up visits (2006-2011) in the Boston Puerto Rican Health Study.Participants/settingParticipants were self-identified Puerto Ricans, aged 45 to 75 years, residing in Boston, Massachusetts, or the surrounding area (n = 1,126).Main outcome measuresMetS components were fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic and diastolic blood pressures, and waist circumference.Statistical analysisBaseline intake of foods reported in a semiquantitative food frequency questionnaire were expressed as servings/day, and protein-rich foods were categorized as unprocessed white meat, unprocessed red meat, processed meat, milk and yogurt, cheese, fish and seafood, beans, nuts, and eggs. Associations between each continuous protein food group and continuous 2-year change in MetS components were assessed using linear mixed models adjusted for socioeconomic and behavioral factors, and other dietary sources.ResultsThe top contributors to total protein intake were unprocessed red meat (13.3%) and unprocessed poultry (13.0%), and the lowest were eggs (2.92%) and nuts (0.91%). Higher intake of processed meats was associated with an increase in waist circumference over 2 years (β = 1.28; standard error [SE] = 0.63), whereas higher intake of fish and seafood was associated with a decrease in waist circumference (β = -3.47; SE = 1.39). Intake of unprocessed poultry was associated with a decrease in triglycerides (β = -24.5; SE = 9.13). No other significant associations were observed between protein sources and 2-year changes in MetS components.ConclusionsConsuming less processed meat and more fish and seafood and unprocessed poultry was associated with decreases in waist circumference and triglycerides among US mainland Puerto Ricans. Other dietary protein sources were not related to cardiometabolic health.

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Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study.

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Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study.

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