Body Mass Index Is Associated with Dietary Patterns and Health Conditions in Georgia Centenarians

Associations between body mass index (BMI) and dietary patterns and health conditions were explored in a population-based multiethnic sample of centenarians from northern Georgia. BMI ≤20 and ≥25 was prevalent in 30.9% and 25.3% of study participants, respectively. In a series of logistic regression analyses controlled for gender and place of residence, the probability of having BMI ≥25 was increased by being black versus white and having a low citrus fruit, noncitrus fruit, orange/yellow vegetable or total fruit and vegetable intake. The probability of having BMI ≤20 was not associated with dietary intake. When controlled for race, gender, residence, and total fruit and vegetable intake, BMI ≥25 was an independent risk factor for diabetes or having a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, whereas BMI ≤20 was a risk factor for anemia. Given the many potential adverse consequences of under- and overweight, efforts are needed to maintain a healthy weight, even in the oldest old

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation

Bone Turnover is not Influenced by Serum 25-Hydroxyvitamin D in Pubertal Healthy Black and White Children

Low serum 25-hydroxyvitamin D [25(OH)D] is common in healthy children particularly in blacks. However, serum 25(OH)D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25(OH)D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25(OH)D and changes in serum 25(OH)D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D3 supplementation (0 to 4000 IU/d). Serum 25(OH)D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12 weeks. Relationships among baseline 25(OH)D and bone biomarkers, and between changes over 12 weeks were determined and tested for effects of race, sex, latitude, and baseline 25(OH)D. Median 25(OH)D was 27.6 ng/mL (n=318, range 10.1–46.0 ng/mL) at baseline and 34.5 ng/mL (n=302, range 9.7–95.1 ng/mL) at 12 weeks. Neither baseline nor change in 25(OH)D over 12 weeks were associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25(OH)D. Serum 25(OH)D in the range of 10-46 ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents

Cognitive Function, Physical Performance, Health, and Disease: Norms From the Georgia Centenarian Study

This study provides, for the first time, normative data on cognitive functioning and physical performance, health and health behaviors, and diseases from a population-based sample of 244 centenarians and near-centenarians (M age = 100.5 years, range 98–108, 84.8% women, 21.3% African American) from the Georgia Centenarian Study. Data are presented by the four key dimensions of gender, race, residence, and educational attainment. Results illustrate the profound range of functioning in this age group and indicate considerable differences as a function of each dimension. Bivariate models generally suggest that cognitive functioning and physical performance is higher for men than women; whites than African Americans; community than facility residents; and those with more than high school education than those with less than high school education. Multivariate models elaborate that differences in educational attainment generally account for the largest proportion of variance in cognitive functioning and residential status generally accounts for the largest proportion of variance in physical performance measures. Addition of health variables seldom increases variance accounted for in each domain beyond these four dimensions

Diabetes mellitus in centenarians

OBJECTIVES: Describe prevalence of diabetes mellitus among centenarians. DESIGN: Cross-sectional, population-based. SETTING: 44 counties in northern Georgia. PARTICIPANTS: 244 centenarians (aged 98-108, 15.8% men, 20.5% African-American, 38.0% community-dwelling) from the Georgia Centenarian Study (2001-2009). MEASUREMENTS: Nonfasting blood samples assessed HbA(1c) and relevant clinical parameters. Demographic, diagnosis, and diabetes complications covariates were assessed. RESULTS: 12.5% of centenarians were known to have diabetes. Diabetes was more prevalent among African-Americans (27.7%) than Whites (8.6%, p=.0002). There were no differences between men (16.7%) and women (11.7%, p=.414), centenarians living in the community (10.2%) or facilities (13.9%, p=.540). Diabetes was more prevalent among overweight/obese (23.1%) than non-overweight (7.1%, p=.002) centenarians. Anemia (78.6% versus 48.3%, p=.004) and hypertension (79.3% versus 58.6%, p=.041) were more prevalent among centenarians with diabetes than without and centenarians with diabetes took more nonhypoglycemic medications(8.6 versus 7.0, p=.023). No centenarians with hemoglobin A1c < 6.5% had random serum glucose levels above 200 mg/dl. Diabetes was not associated with 12 month all-cause mortality, visual impairment, amputations, cardiovascular disease or neuropathy. 37% of centenarians reported onset before age 80 (survivors), 47% between 80 and 97 years (delayers) and 15% age 98 or older (escapers). CONCLUSION: Diabetes is a risk factor for cardiovascular disease and mortality, but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of diabetes were observed in centenarians

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed

HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging

The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. © 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

Common Genetic Variants Associate with Serum Phosphorus Concentration

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR &lt;45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P &lt; 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation