25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966.
ABSTRACT: Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)(2)) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = -0.4%, 95% confidence interval: -0.6, -0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = -0.3%, 95% confidence interval -0.6, -0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL.
Project description:Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In women, higher plasma 25-hydroxyvitamin D (25(OH)D) has been shown to be associated with longer telomere length, but the relationship has not been assessed in men.We conducted a cross-sectional analysis of 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D) and relative leukocyte telomere length (LTL) among 2483 men [1832 men for 1,25(OH)2D] who were selected as cases and controls in three studies of telomeres and cancer nested within the Health Professionals Follow-up Study. We also genotyped 95 SNPs representing common genetic variation in vitamin D pathway genes. LTL was measured by quantitative PCR, and z-scores within each study were calculated. Associations were assessed by linear as well as logistic regression adjusting for age and other potential confounders.Age (P-trend < 0.0001), pack-years of smoking (P-trend = 0.04) and body mass index (P-trend = 0.05) were inversely associated with LTL. Neither 25(OH)D nor 1,25(OH)2D was associated with LTL (multivariable-adjusted P-trend 0.69 and 0.41, respectively, for the linear regression model). One SNP in the retinoid X receptor alpha gene was associated with long LTL (P = 0.0003).In this cross-sectional study of men, 25(OH)D and 1,25(OH)2D were not associated with relative LTL.
Project description:Telomere length is considered a biomarker of biological aging. Shorter telomeres and obesity have both been associated with age-related diseases. To evaluate the association between various indices of obesity with leukocyte telomere length (LTL) in childhood, data from 1,396 mother-child pairs of the multi-centre European birth cohort study HELIX were used. Maternal pre-pregnancy body mass index (BMI) and 4 adiposity markers in children at age 8 (6-11) years were assessed: BMI, fat mass, waist circumference, and skinfold thickness. Relative LTL was obtained. Associations of LTL with each adiposity marker were calculated using linear mixed models with a random cohort effect. For each 1?kg/m² increment in maternal pre-pregnancy BMI, the child's LTL was 0.23% shorter (95%CI: 0.01,0.46%). Each unit increase in child BMI z-score was associated with 1.21% (95%CI: 0.30,2.11%) shorter LTL. Inverse associations were observed between waist circumference and LTL (-0.96% per z-score unit; 95%CI: -2.06,0.16%), and skinfold thickness and LTL (-0.10% per z-score unit; 95%CI: -0.23,0.02%). In conclusion, this large multicentric study suggests that higher child adiposity indicators are associated with short telomeres in children, and that associations are stronger for child BMI than for maternal pre-pregnancy BMI.
Project description:<h4>Background</h4>Low vitamin D status, adiposity, and at-risk lipid profile are associated with adverse health consequences. This study aimed to assess serum 25(OH)D concentration of Indigenous (Orang Asli) adults and to determine the associations between serum 25(OH)D with adiposity and lipid profile, respectively.<h4>Methods</h4>This cross-sectional study was conducted among 555 (164 men, 391 women) Orang Asli adults aged 18-65 years of Jah Hut sub-tribe in Krau Wildlife Reserve (KWR), Peninsular Malaysia. Demographic and socio-economic information were obtained using interviewer-administered questionnaire. Participants were also assessed for serum 25-hydroxyvitamin D (25(OH)D) concentration, adiposity indices (BMI, WC, WHtR, WHR, %BF) and lipid parameters (TC, LDL-C, HDL-C, TG). Data were analyzed using binary logistic regression via SPSS.<h4>Results</h4>The prevalence of suboptimal 25(OH)D concentration was 26.3%, comprising 24.9% insufficiency (50 to <75 nmol/L) and 1.4% deficiency (<50 nmol/L). While men (14-30.5%) were associated with a more proatherogenic lipid profile than women (6.1-14.3%), more women were with central obesity (M: 19.5-46.3%; F: 34.5-49.1%) and suboptimal (<75 nmol/L) vitamin D status (M: 11.6%; F: 32.4%). While suboptimal 25(OH)D concentration was significantly associated with higher odds of at-risk LDL-C (<i>p</i> < 0.01) and obesity (WC, WHtR) (<i>p</i> < 0.05) in men, no significant association was observed for women. Nonetheless, it should be noted that there were only 19 men with suboptimal (<75 nmol/L) vitamin D status.<h4>Conclusions</h4>While suboptimal vitamin D status was relatively low in Orang Asli adults, the prevalence of obesity and undesirable serum lipids were relatively high. The sex-specific associations between vitamin D status with adiposity indices and serum lipids warrant further investigation.
Project description:Background. Vitamin D deficiency is a global health problem. Some evidences indicate its association with metabolic syndrome, type II diabetes, and cardiovascular diseases. In the current study we aim to study the association of vitamin D level and indicators of adiposity in young Saudi females. Subjects and Methods. 87 young healthy Saudi females were recruited from University of Dammam, Dammam, Saudi Arabia. Each subject filled vitamin D questionnaire and had exercise stress test to determine VO2 peak. Body weight, BMI, waist and hip circumference, and ratios were determined. Blood was analyzed for 25-OH vitamin D, glucose, triglycerides, total cholesterol, and differential cholesterol. Results. 25-OH vitamin D/body weight was negatively associated with waist circumference and waist/stature ratio. No significant difference was found between the groups of BMI with regard to the data of questionnaire or 25-OH vitamin D/body weight. Obese and overweight subjects had lower VO2 peak. Conclusion. In young Saudi females we found that the relative value of vitamin D to body weight is a better indicator of vitamin D status particularly in obese subjects and it is negatively associated with adiposity measures of waist circumference and waist/stature ratio.
Project description:Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In the present study, we examined the association between vitamin D and relative leukocyte telomere length by using both plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) biomarkers. Vitamin D biomarker levels and leukocyte telomere length were measured using plasma samples collected in 1989-1990 from participants of the Nurses' Health Study, a study of nurses from 11 US states. In total, 1,424 participants had their 25(OH)D levels assessed and 837 had their 1,25(OH)2D levels assessed. Genotyping was performed on 480 participants on 12 single nucleotide polymorphisms in vitamin D-related genes. Linear and logistic regression models were used. Higher 25(OH)D levels were significantly associated with longer telomere length (P for trend = 0.05), and the odds ratio increased from 1.07 (P = 0.65) when comparing the second lowest quartile of 25(OH)D with the lowest to 1.59 (P = 0.01) when comparing the highest quartile with the lowest. Vitamin D-related single nucleotide polymorphisms and 1,25(OH)2D levels were not significantly associated with telomere length. Total calcium intake significantly modified the association between 25(OH)D and telomere length (P for interaction = 0.05). Higher plasma 25(OH)D levels may be associated with longer telomeres, and this association may be modified by calcium intake.
Project description:BACKGROUND/OBJECTIVES:Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. SUBJECTS/METHODS:Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ?25%; females ?35%; BF2% ?28% and ?38%, respectively), body mass index (BMI) and waist circumference (WC; men ?102?cm; females ?88?cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ?60 years; <70 vs ?70 years). RESULTS:We identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted ?-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (?=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (?=-0.025±0.0008; P=0.005) and WC (?=-0.0011±0.0004; P=0.007). High BF% (BF1%: ?=-0.035±0.011; P=0.002; BF2%: ?=-0.041±0.008; P<0.001) and WC (?=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality. CONCLUSIONS:Obesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.
Project description:OBJECTIVES:Lower vitamin D status has been associated with adiposity in children through adults. However, the evidence of the impact of maternal vitamin-D status during pregnancy on offspring's adiposity is mixed. The objective of this study was to examine the associations between maternal vitamin-D [25(OH)D] status at mid-gestation and neonatal abdominal adipose tissue (AAT) compartments, particularly the deep subcutaneous adipose tissue linked with metabolic risk. METHODS:Participants (N?=?292) were Asian mother-neonate pairs from the mother-offspring cohort, Growing Up in Singapore Towards healthy Outcomes. Neonates born at ?34 weeks gestation with birth weight ?2000?g had magnetic resonance imaging (MRI) within 2-weeks post-delivery. Maternal plasma glucose using an oral glucose tolerance test and 25(OH)D concentrations were measured. 25(OH)D status was categorized into inadequate (?75.0?nmol/L) and sufficient (>75.0?nmol/L) groups. Neonatal AAT was classified into superficial (sSAT), deep subcutaneous (dSAT), and internal (IAT) adipose tissue compartments. RESULTS:Inverse linear correlations were observed between maternal 25(OH)D and both sSAT (r?=?-0.190, P?=?0.001) and dSAT (r?=?-0.206, P?<?0.001). Each 1?nmol/L increase in 25(OH)D was significantly associated with reductions in sSAT (??=?-0.14 (95% CI: -0.24, -0.04) ml, P?=?0.006) and dSAT (??=?-0.04 (-0.06, -0.01)?ml, P?=?0.006). Compared to neonates of mothers with 25(OH)D sufficiency, neonates with maternal 25(OH)D inadequacy had higher sSAT (7.3 (2.1, 12.4) ml, P?=?0.006), and dSAT (2.0 (0.6, 3.4) ml, P?=?0.005) volumes, despite similar birth weight. In the subset of mothers without gestational diabetes, neonatal dSAT was also greater (1.7 (0.3, 3.1) ml, P?=?0.019) in neonates with maternal 25(OH)-inadequacy. The associations with sSAT and dSAT persisted even after accounting for maternal glycemia (fasting and 2-h plasma glucose). CONCLUSIONS:Neonates of Asian mothers with mid-gestation 25(OH)D inadequacy have a higher abdominal subcutaneous adipose tissue volume, especially dSAT (which is metabolically similar to visceral adipose tissue in adults), even after accounting for maternal glucose levels in pregnancy.
Project description:Previous Studies have mapped putative loci that may probably regulate leukocyte telomere length (LTL). The strongest associations with LTL were reported for SNP rs12696304 and rs16847897 near the non-coding Ribose Nucleic Acid (RNA) molecule component (TERC) of telomerase enzyme on 3q26. It is unclear whether these identified loci coding functional components of telomerase, exert a similar effect on LTL in other populations or influence risk factors of Type 2 Diabetes Mellitus (T2DM). The present study was performed to: study the influence of TERC polymorphisms on LTL, human telomerase reverse transcriptase (hTERT), indices of obesity and explore the potential associations with T2DM. 225 T2DM patients and 245 age and sex matched controls were studied. Allelic Discrimination (AD) genotyping was utilized to determine TERC SNPs [rs12696304 and rs16847897]. hTERT, adiponectin, Insulin, Homeostasis Model Assessment (HOMA-IR), and LTL were measured. Body Mass Index (BMI) and waist circumference (WC) were recorded. [CC] genotype of rs16847897 was significantly associated with shorter LTL [OR = 1.6, p = 0.004], lower hTERT levels [OR = 0.4, p = 0.006], higher BMI [OR = 2.2, p = 0.006], larger WC [OR = 23.4, p = 0.007] and hypo-adiponectemia [OR = 0.6, p = 0.006]. [GG] genotype of rs12696304 was also significantly associated with shorter LTL [OR = 1.5, p = 0.004], lower hTERT [OR = 0.7, p = 0.006] but with larger WC[OR = 5.3, p = 0.004]. [CC] genotype of rs16847897 and [GG] genotype of rs12696304 together increased the risk of T2DM significantly [OR = 1.7, p = 0.004]. We provide insights connecting a structure that is critically involved in maintaining genomic stability with obesity and T2DM. Given the central role of telomere length in determining telomere function our findings may expand our understanding of the pathological mechanisms underlying age associated conditions such as T2DM.
Project description:<h4>Background</h4>Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL).<h4>Methodology</h4>We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D.<h4>Findings</h4>After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (? per standard deviation increase: -0.01; SE: 0.02; P?=?0.52). Similarly, the T2D genetic score was not associated with LTL (? per standard deviation increase: -0.006; SE: 0.02; P?=?0.69).<h4>Conclusions</h4>In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.
Project description:<h4>Background</h4>Low vitamin D status may be pronounced in Arctic populations due to limited sun exposure and decreasing intake of traditional food.<h4>Objective</h4>To investigate serum 25(OH)D3 as a measure of vitamin D status among adult Inuit in Greenland, predictors of low serum 25(OH)D3 concentrations and the trend from 1987 to 2005-2010.<h4>Design</h4>A total of 2877 randomly selected Inuit (? 18 years) from the Inuit Health in Transition study were included. A sub-sample (n = 330) donated a blood sample in 1987 which allowed assessment of time trends in vitamin D status.<h4>Results</h4>The geometric mean serum 25(OH)D3 (25[OH]D2 concentrations were negligible and not reported) in 2005-2010 was lowest among the 18-29 year old individuals (30.7 nmol/L; 95% CI: 29.7; 31.7) and increased with age. In all age-groups it decreased from 1987 to 2005-2010 (32%-58%). Low 25(OH)D3 concentrations (<50 nmol/L) were present in 77% of the 18-29 year old and decreased with age. A characteristic seasonal variation in 25(OH)D3 concentrations was observed (range 33.2-57.1 nmol/L, p<0.001), with the highest concentrations in August to October. Age (2.0% per year increase; CI: 1.7, 2.2), female gender (7.1%; CI: 2.0; 12.5), alcohol intake (0.2% per increase in drinks/week; 0.0; 0.4), and traditional diet (10.0% per 100 g/d increase; CI: 7.9; 12.1) were associated with increased serum 25(OH)D3, whereas smoking (-11.6%; CI: -16.2; -6.9), BMI (-0.6%; CI: -1.1; -0.2) and latitude (-0.7% per degree increase; CI: -1.3; -0.2) were associated with decreased concentrations.<h4>Conclusion</h4>We identified a remarkable decrease in vitamin D status from 1987 to 2005-2010 and a presently low vitamin D status among Inuit in Greenland. A change away from a traditional diet may well explain the observed decline. The study argues for the need of increased dietary intake of vitamin D and supplementation might be considered.