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Insulin resistance in Chileans of European and indigenous descent: evidence for an ethnicity x environment interaction.

ABSTRACT: BACKGROUND: Effects of urbanisation on diabetes risk appear to be greater in indigenous populations worldwide than in populations of European origin, but the reasons are unclear. This cross-sectional study aimed to determine whether the effects of environment (Rural vs. Urban), adiposity, fitness and lifestyle variables on insulin resistance differed between individuals of indigenous Mapuche origin compared to those of European origin in Chile. METHODOLOGY/PRINCIPAL FINDINGS: 123 Rural Mapuche, 124 Urban Mapuche, 91 Rural European and 134 Urban European Chilean adults had blood taken for determination of HOMA-estimated insulin resistance (HOMA(IR)) and underwent assessment of physical activity/sedentary behaviour (using accelerometry), cardiorespiratory fitness, dietary intake and body composition. General linear models were used to determine interactions with ethnicity for key variables. There was a significant "ethnicity x environment" interaction for HOMA(IR) (Mean±SD; Rural Mapuche: 1.65±2.03, Urban Mapuche: 4.90±3.05, Rural European: 0.82±0.61, Urban European: 1.55±1.34, p((interaction))?=?0.0003), such that the effect of urbanisation on HOMA(IR) was greater in Mapuches than Europeans. In addition, there were significant interactions (all p<0.004) with ethnicity for effects of adiposity, sedentary time and physical activity on HOMA(IR,) with greater effects seen in Mapuches compared to Europeans, an observation that persisted after adjustment for potential confounders. CONCLUSIONS/SIGNIFICANCE: Urbanisation, adiposity, physical activity and sedentary behaviour influence insulin resistance to a greater extent in Chilean Mapuches than Chileans of European descent. These findings have implications for the design and implementation of lifestyle strategies to reduce metabolic risk in different ethnic groups, and for understanding of the mechanisms underpinning human insulin resistance.

SUBMITTER: Celis-Morales CA

PROVIDER: S-EPMC3169638 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Insulin resistance in Chileans of European and indigenous descent: evidence for an ethnicity x environment interaction.

Celis-Morales Carlos A CA Perez-Bravo Francisco F Ibañes Luis L Sanzana Ruth R Hormazabal Edison E Ulloa Natalia N Calvo Carlos C Bailey Mark E S ME Gill Jason M R JM

PloS one 20110908 9

<h4>Background</h4>Effects of urbanisation on diabetes risk appear to be greater in indigenous populations worldwide than in populations of European origin, but the reasons are unclear. This cross-sectional study aimed to determine whether the effects of environment (Rural vs. Urban), adiposity, fitness and lifestyle variables on insulin resistance differed between individuals of indigenous Mapuche origin compared to those of European origin in Chile.<h4>Methodology/principal findings</h4>123 Ru ...[more]

PMID: 21931814

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Project description:A more thorough understanding of the genetic architecture underlying obesity-related lipid disorders could someday facilitate cardiometabolic risk reduction through early clinical intervention based upon improved characterization of individual risk. In recent years, there has been tremendous interest in understanding the endocannabinoid system as a novel therapeutic target for the treatment of obesity-related dyslipidemia.N-arachidonylethanolamine activates G-protein-coupled receptors within the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is a primary catabolic regulator of N-acylethanolamines, including arachidonylethanolamine. Genetic variants in FAAH have inconsistently been associated with obesity. It is conceivable that genetic variability in FAAH directly influences lipid homeostasis. The current study characterizes the relationship between FAAH and obesity-related dyslipidemia, in one of the most rigorously-phenotyped obesity study cohorts in the USA.Members of 261 extended families (pedigrees ranging from 4 to 14 individuals) were genotyped using haplotype tagging SNPs obtained for the FAAH locus, including 5 kb upstream and 5 kb downstream. Each SNP was tested for basic obesity-related phenotypes (BMI, waist and hip circumference, waist:hip ratio, fasting glucose, fasting insulin and fasting lipid levels) in 1644 individuals within these 261 families. Each SNP was also tested for association with insulin responsiveness using data obtained from a frequently sampled intravenous glucose tolerance test in 399 individuals (32 extended families).A well characterized coding SNP in FAAH (rs324420) was associated with increased BMI, increased triglycerides, and reduced levels of high-density lipoprotein cholesterol. Mean (standard deviation) high-density lipoprotein cholesterol level was 40.5 (14.7) mg/dl for major allele homozygotes, 39.1 (10.4) mg/dl for heterozygotes, and 34.8 (8.1) mg/dl for minor allele homozygotes (p < 0.01, Family-Based Association Test). This SNP was not associated with insulin sensitivity, acute insulin response to intravenous glucose, glucose effectiveness or glucose disposition index.Genetic variability in FAAH is associated with dyslipidemia, independent of insulin response.

Project description:Obesity-insulin connections have been considered potential risk factors for postmenopausal breast cancer, and the association between insulin resistance (IR) genotypes and phenotypes can be modified by obesity-lifestyle factors, affecting breast cancer risk. In this study, we explored the role of IR in those pathways at the genome-wide level. We identified IR-genetic factors and selected lifestyles to generate risk profiles for postmenopausal breast cancer. Using large-scale cohort data from postmenopausal women in the Women's Health Initiative Database for Genotypes and Phenotypes Study, our previous genome-wide association gene-behavior interaction study identified 58 loci for associations with IR phenotypes (homeostatic model assessment-IR, hyperglycemia, and hyperinsulinemia). We evaluated those single-nucleotide polymorphisms (SNP) and additional 31 lifestyles in relation to breast cancer risk by conducting a two-stage multimodal random survival forest analysis. We identified the most predictive genetic and lifestyle variables in overall and subgroup analyses [stratified by body mass index (BMI), exercise, and dietary fat intake]. Two SNPs (LINC00460 rs17254590 and MKLN1 rs117911989), exogenous factors related to lifetime cumulative exposure to estrogen, BMI, and dietary alcohol consumption were the most common influential factors across the analyses. Individual SNPs did not have significant associations with breast cancer, but SNPs and lifestyles combined synergistically increased the risk of breast cancer in a gene-behavior, dose-dependent manner. These findings may contribute to more accurate predictions of breast cancer and suggest potential intervention strategies for women with specific genetic and lifestyle factors to reduce their breast cancer risk. SIGNIFICANCE: These findings identify insulin resistance SNPs in combination with lifestyle as synergistic factors for breast cancer risk, suggesting lifestyle changes can prevent breast cancer in women who carry the risk genotypes.

Project description:ImportanceIndividuals of African descent have been reported to be at higher risk for becoming visually impaired from glaucoma compared with individuals of European descent.ObjectiveTo investigate racial differences in longitudinal visual field variability and their impact on time to detect visual field progression.Design, setting, and participantsThis multicenter prospective observational cohort study included 236 eyes of 173 individuals of European descent and 235 eyes of 171 individuals of African descent followed up for a mean (SD) time of 7.5 (3.4) years.Main outcomes and measuresDifferences in test-retest variability and simulated time to detect progression in individuals of African descent and of European descent with glaucoma. Standard automated perimetry mean deviation values were regressed over time for each eye, and SD of the residuals was used as a measure of variability. Distributions of residuals were used in computer simulations to reconstruct "real-world" standard automated perimetry mean deviation trajectories under different assumptions about rate of change and frequency of testing. Times to detect progression were obtained for the simulated visual fields.ResultsAmong the 344 patients, the mean (SD) age at baseline was 60.2 (10.0) and 60.6 (9.0) years for individuals of African descent and of European descent, respectively; 94 (52%) and 86 (48%) of individuals of African descent and of European descent were women, respectively. The mean SD of the residuals was larger in eyes of individuals of African descent vs those of European descent (1.45 [0.83] dB vs 1.12 [0.48] dB; mean difference: 0.33 dB; 95% CI of the difference, 0.21-0.46; P < .001). The eyes in individuals of African descent had a larger increase in variability with worsening disease (P < .001). When simulations were performed assuming common progression scenarios, there was a delay to detect progression in eyes of individuals of African descent compared with those of European descent. For a scenario with baseline mean deviation of -10 dB and rate of change of -0.5 dB/y, detection of progression in individuals of African descent was delayed by 3.1 (95% CI, 2.9-3.2) years, when considered 80% power and annual tests.Conclusions and relevancePatients of African descent with glaucoma showed increased visual field variability compared with those of European descent, resulting in delayed detection of progression that may contribute to explain higher rates of glaucoma-related visual impairment in individuals of African descent compared with those of European descent with glaucoma.

Dataset Information

Insulin resistance in Chileans of European and indigenous descent: evidence for an ethnicity x environment interaction.

Publications

Insulin resistance in Chileans of European and indigenous descent: evidence for an ethnicity x environment interaction.

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