Dataset Information

Specific Genotypes Associated with Differences in Fasting Insulin Levels and Body Mass Index in Healthy Young Males: Implications for Gene-Nutrient Interactions-an Exploratory Study.

ABSTRACT:

Background

Genetic variation may significantly impact an individual's susceptibility to diseases, particularly when combined with specific nutrients. Additionally, genetic variations can lead to interindividual differences in metabolic responses.

Objective

The present study explores the association between gene variants and observed interindividual differences in metabolic responses.

Methods

The study included 30 healthy males (aged 20-34) who underwent a fasting period and subsequently consumed a standardized meal. Blood samples were collected both before and after the meal to assess metabolic changes. BMI served as an indirect measure for assessing physiological responses associated with body composition. Appetite changes were assessed using an online Visual Analog 100-point Scale. Buccal swabs were collected to analyze genetic variants in single nucleotide polymorphisms (SNPs).

Results

The data underwent multiple regression analysis, revealing significant associations with 3 SNPs and their metabolic status: the insulin-receptor substrate 1 (IRS1) gene variant rs2943641, genotypes CT and CC, with elevated fasting insulin levels (R² = 0.639, P = < 0.0001); the mitochondrial uncoupling protein 1 (UCP1) gene variant rs1800592, genotypes GG and GA, with increased BMI (R² = 0.261, P = 0.007); and the peroxisome proliferator-activated receptor γ2 (PPARγ2) gene variant rs1801282, genotypes GG and GC, with increased BMI (R² = 0.200, P = 0.024).

Conclusions

Therefore, our study established significant associations between these 3 SNPs and differences in fasting insulin levels and BMI within our cohort.

SUBMITTER: Brown JE

PROVIDER: S-EPMC10663744 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Specific Genotypes Associated with Differences in Fasting Insulin Levels and Body Mass Index in Healthy Young Males: Implications for Gene-Nutrient Interactions-an Exploratory Study.

Brown Julie E JE Pham Toan T Burden Hannah H Braakhuis Andrea J AJ

Current developments in nutrition 20231021 11

<h4>Background</h4>Genetic variation may significantly impact an individual's susceptibility to diseases, particularly when combined with specific nutrients. Additionally, genetic variations can lead to interindividual differences in metabolic responses.<h4>Objective</h4>The present study explores the association between gene variants and observed interindividual differences in metabolic responses.<h4>Methods</h4>The study included 30 healthy males (aged 20-34) who underwent a fasting period and ...[more]

PMID: 38026570

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Project description:Background/objectivesObesity is often considered to increase the risk for premature mortality. Higher fasting insulin and c-reactive protein are associated with higher body mass index (BMI) and all-cause mortality, so may confound the association between obesity and mortality. Our objective was to determine the independent associations between BMI, fasting insulin, c-reactive protein, and all-cause mortality in a general population sample.MethodsThis prospective cohort study included non-institutionalized US adults (≥20 years) from the National Health and Nutrition Examination Surveys 1999-2000 to 2013-2014. The main exposures of interest were BMI, fasting insulin, c-reactive protein. Mortality data were obtained through linking participants to the National Death Index (ending December 31, 2015).ResultsThere were 12,563 participants with a median age of 45 years (range 20-85) and 47.9% were male. The median BMI was 27 kg/m2 (IQR 24-32), median fasting insulin was 54 pmol/L (IQR 35-87), and median c-reactive protein was 1.9 mg/L (IQR 0.8-4.4). In a Cox model adjusted for age, biological sex, cigarette smoking, and ten chronic conditions, higher BMI parameterized with quadratic and linear terms was not associated with mortality. When fasting insulin and the natural logarithm of c-reactive protein were included in the model, an inverse association between BMI and mortality was present (compared to the referent category of 5th percentile: 1st percentile, HR 1.10, 95% CI 1.06-1.13; 99th percentile, HR 0.48, 95% CI 0.34-0.69). In contrast, higher levels of fasting insulin and c-reactive protein were associated with an increased risk of mortality (for fasting insulin: 1st percentile, HR 0.98, 95% CI 0.97-0.99; 99th percentile, HR 1.83, 95% CI 1.48-2.26; for c-reactive protein, 1st percentile, HR 0.87, 95% CI 0.84-0.90; 99th percentile, HR 2.77, 95% CI 2.12-3.62).ConclusionsHigher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.

Project description:Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders (n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([13C]glucose and [6,6-2H2]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower (P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA (P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate (r = -0.738) and Δγ-glutamylalanine (r = -0.810), were inversely associated (P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate (r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate (r = -0.738) were inversely associated (P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.

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Project description:BACKGROUND:Perfluorooctanoate (PFOA) has been used extensively in the manufacture of both commercial and household products. PFOA serum concentrations have been associated with adverse health effects, including lower body mass in children and infants. OBJECTIVE:To determine if there is an association between serum PFOA concentration and body mass, serum insulin and lipid profile in exposed young girls. METHODS:We conducted a cross-sectional study of PFAS environmental biomarkers and insulin resistance in 6 to 8 year-old girls from Greater Cincinnati (n=353). In 2004-2006, blood samples were obtained to measure polyfluoroalkyl substances (PFAS), fasting insulin, glucose and lipids. Clinical exams included anthropometric measurements and pubertal maturation staging. Linear regression and mediation analyses, specifically structural equation modeling (SEM), were used to determine the strength and direction of the relationships between PFAS, pubertal maturation status, body mass index (BMI), cholesterol and insulin resistance. RESULTS:The median PFOA (7.7ng/ml) was twice the National Health and Nutrition Examination Survey (2005-2006). Only PFOA, a PFAS sub-species, showed statistically significant relationships with the outcomes. In regression models, PFOA was associated with decreased BMI and waist-to-height ratio (p=0.0008; p=0.0343), HDL-cholesterol (p=0.0046) and had a borderline inverse association with the HOMA Index of insulin resistance (p=0.0864). In SEM, PFOA retained an inverse relationship with BMI (p<0.0001) but the relationships with HOMA and HDL-cholesterol were no longer statistically significant. Pubertal initiation (Tanner breast or pubic stage 2 or greater) and BMI were associated with increased HOMA Index (p<0.0001). CONCLUSIONS:These findings suggest PFOA exposure in young girls affects both BMI and ultimately insulin resistance. In mediation analysis with puberty in the model, the direct effects of PFOA on insulin resistance and were reduced.

Dataset Information

Specific Genotypes Associated with Differences in Fasting Insulin Levels and Body Mass Index in Healthy Young Males: Implications for Gene-Nutrient Interactions-an Exploratory Study.

Background

Objective

Methods

Results

Conclusions

Publications

Specific Genotypes Associated with Differences in Fasting Insulin Levels and Body Mass Index in Healthy Young Males: Implications for Gene-Nutrient Interactions-an Exploratory Study.

Similar Datasets

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