Obesity, metabolic health, and the risk of end-stage renal disease.

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by the presence or absence of the metabolic syndrome and adjusted for demographic, lifestyle, and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95% CI 0.52, 0.95) but not those with (hazard ratio, 1.06) the metabolic syndrome. In models stratified by weight and metabolic health, compared with normal weight (BMI 18.5-24.9 kg/m2) participants without the metabolic syndrome the overweight individuals (BMI 25-29.9) and obese individuals (BMI of 30 or more) with the metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with the metabolic syndrome.

Bone Mineral Content as a Driver of Energy Expenditure in Prepubertal and Early Pubertal Boys.

OBJECTIVE: To examine the associations of bone and bone-secreted factors with measures of energy metabolism in prepubertal and early pubertal boys. STUDY DESIGN: Participants in this cross-sectional, observational study included 37 (69% black, 31% white) boys, aged 7-12 years (Tanner stage

Fibroblast growth factor-21, body composition, and insulin resistance in pre-pubertal and early pubertal males and females.

OBJECTIVE: Accumulating evidence derived primarily from animal models suggests that fibroblast growth factor-21 (FGF-21) may affect the musculoskeletal system via effects on the capacity of tissues to respond to insulin. A proportion of musculoskeletal properties and underpinnings of promoting/preventing insulin resistance are established early in the pubertal transition. Thus, the objective of this study was to test the hypothesis that insulin resistance and/or obesity will promote greater FGF-21 concentration which will be inversely associated with musculoskeletal parameters [lean mass and bone mineral content (BMC)] in pre-/early pubertal children. Given the sexual dimorphic nature of musculoskeletal development of fat mass accrual, differences by obesity status and sex were also investigated. DESIGN: Cross-sectional. PATIENTS: Children ages 7-12 years (n = 69, 38% male, 48% non-Hispanic black, 45% obese). MEASUREMENTS: Fasting FGF-21, glucose and insulin measures were obtained. An estimate of insulin resistance was derived using the homoeostatic model assessment of insulin resistance (HOMA-IR). Body composition (BMC, lean mass and fat mass) was assessed by DXA. Multivariate regression analysis was used to evaluate the influence of FGF-21 on BMC, lean mass and HOMA-IR as dependent variables. Obesity status was established based on BMI z-score. RESULTS: FGF-21 concentrations did not differ by obesity status or by sex. There was an inverse association between FGF-21 and BMC among nonobese individuals (P = 0·01) and an inverse association between FGF-21 and lean mass among females (P = 0·02), which were both independent of fat mass. FGF-21 was inversely associated with HOMA-IR in males, but not females (P = 0·04). CONCLUSIONS: The existence of relationships of FGF-21 with musculoskeletal parameters and insulin resistance raises the possibility of crosstalk between these systems. These findings suggest that circulating FGF-21 may differ in its association with bone, lean mass and insulin resistance depending on sex and weight status.

Vitamin D and calcium-sensing receptor polymorphisms differentially associate with resting energy expenditure in peripubertal children.

Given that calcium metabolism is influenced by genes and is tightly linked to energy-utilizing pathways, this study evaluated the association of single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) with resting energy expenditure (REE). In 273 boys and girls, 7-12 years of age, cross-sectional REE was measured via indirect calorimetry, body composition by DXA, and dietary measures by 24-h recall. SNPs for VDR Cdx-2 (rs11568820) and CASR A986S (rs1801725) were genotyped using the Illumina Golden Gate assay. Multiple linear regression models were used to determine the association between SNPs and REE. African American carriers of the 'A' VDR Cdx2 allele had increased levels of REE in the overall sample, and this association was apparent among participants with an adiposity level of <25 % and 30 % body fat in males and females, respectively. For CASR, an association between carriers of the 'A' allele and REE was observed only in those in the upper median of calcium intake. VDR and CASR variants are associated with REE in children and are influenced by levels of calcium intake and adiposity. Our results bring awareness to mechanisms underlying the regulation of REE and biological and dietary influential factors.

Getting to the height of the matter: the relationship between stature and adiposity in pre-pubertal children.

OBJECTIVE: Height has been inversely associated with cardiometabolic disease, with adiposity as the proposed contributor. Childhood represents a time when underlying metabolic pathways converge to determine growth. Although the extent to which influence is relevant, insulin, as a key growth signaling factor, likely provides key insight into mechanisms linking height and adiposity. Insulin concentration displays well-established sex and racial differences, with hyperinsulinemia more common among African Americans (AA) females relative to European Americans (EA). The objective of our study was to evaluate the relationship between height and adiposity in children. In addition, a secondary objective was to evaluate potential moderation by insulin concentration. DESIGN: Seventy-two pre-pubertal children aged 4-10 years (mu = 6.6 +/- .2) participated. MAIN OUTCOME MEASURES: Percent fat was assessed by DXA and fasting insulin by serum assay. RESULTS: Height was positively associated with percent fat in the overall sample (P = .04). When evaluated according to age, an association was identified at age seven years (P = .02). When evaluated by sex, a positive relationship was apparent only in AA girls (P = .05). Inclusion of insulin in the model attenuated all significant associations, barring marginal significance in those aged seven years (P = .08). CONCLUSIONS: A positive relationship between height and adiposity is apparent, particularly among those in younger years, which is contrary to what has been consistently reported in adults. Interestingly, age seven years was identified as a point of race-associated divergence in body composition. The degree to which growth-related processes in childhood underlie developmental origins of health disparities warrants further study.

Reduced carbohydrate diet to improve metabolic outcomes and decrease adiposity in obese peripubertal African American girls.

OBJECTIVE: Obesity prevalence among African American (AA) girls is higher than that in other groups. Because typical energy-restriction obesity treatment strategies have had limited success, alterations in macronutrient composition may effectively improve metabolic outcomes in this population and affect future body composition trajectories. The objective was to evaluate the efficacy of a moderately restricted carbohydrate (CHO) versus a standard CHO diet on weight/fat loss and metabolic parameters in overweight/obese AA girls ages 9 to 14 years. METHODS: A total of 26 AA girls (ranging from 92nd body mass index percentile and above) were assigned to either a reduced- (SPEC: 42% energy from CHO, n = 12) or a standard- (STAN: 55% of energy from CHO, n = 14) CHO diet (protein held constant) for 16 weeks. All of the meals were provided and clinically tailored to meet the estimated energy requirements (resting energy expenditure × 1.2 in eucaloric phase and resting energy expenditure × 1.2 - 1000 kcal in energy deficit phase). The first 5 weeks encompassed a eucaloric phase evaluating metabolic changes in the absence of weight change. The subsequent 11 weeks were hypocaloric (1000 kcal/day deficit) to promote weight/fat loss. Meal tests were performed during the eucaloric phase for metabolic analyses. Dual-energy x-ray absorptiometry was used to evaluate body composition. RESULTS: Both groups experienced reductions in weight/adiposity, but the difference did not reach significance. The solid meal test indicated improved glucose/insulin homeostasis on the SPEC diet up to 3 hours postingestion. In addition, significantly lower triglycerides (P < 0.001) were observed on the SPEC diet. CONCLUSIONS: Dietary CHO reduction favorably influences metabolic parameters but did not result in greater weight/fat loss relative to a standard diet in obese AA girls. Future research is needed to determine long-term effectiveness of a reduced CHO diet on glucose and insulin homeostasis and how it may apply to weight maintenance/fat loss during development alone and/or in combination with additional weight loss/metabolic improvement strategies.

Shorter sleep may be a risk factor for impaired bone mass accrual in childhood.

The purpose of the study was to investigate whether sleep duration during early childhood was associated with fat mass and bone mineral content (BMC). BMC and fat mass were measured by dual-energy X-ray absorptiometry in children (n=336) aged 4-12 yr. Sleep was quantified according to parental report of hours slept at night and napping. The relationship between sleep pattern and body composition was tested using analysis of variance including confounding factors. Based on the sample distribution, children were grouped into tertiles of sleep duration. BMC was greater in children with longer sleep duration (p=0.02). Age was inversely associated with sleep duration; therefore, the sample was analyzed by age category using age 7 yr as a cut-off point. The relationship remained significant only among younger children. Napping was positively associated with BMC (p=0.001). Sleep duration was not associated with fat parameters. Longer sleep duration may allow for optimal energy resource partitioning in which bone is favored. Sleep duration of less than 8h may impair bone mass accrual, particularly during periods of rapid growth.

Associations among calcium intake, resting energy expenditure, and body fat in a multiethnic sample of children.

OBJECTIVE: The objective was to determine if calcium intake was associated with resting energy expenditure (REE) and body fat in children after accounting for ancestral genetic background. STUDY DESIGN: Participants included 315 children. REE, body composition, and dietary calcium were assessed by indirect calorimetry, dual-energy x-ray absorptiometry, and 24-hour recalls, respectively. Structural equations modeling assessed the relationships among REE, calcium intake, and body fat. RESULTS: There were positive associations between calcium intake and REE (P<.01) and between REE and total body fat (P<.0001). There was indirect effect of calcium intake on total body fat (P<.01). There were positive associations between calcium intake and REE (P<.01), and a trend toward an association of calcium intake and total body fat (P=.065) among boys only, whereas the only significant relationship among girls was an association of REE on total body fat (P<.0001). CONCLUSIONS: REE was associated with calcium intake and mediated a relationship between calcium intake and total body fat. These findings suggest calcium intake may play a role in fat accumulation and energy balance through its effects on REE, especially in boys.

Does fat fuel the fire: independent and interactive effects of genetic, physiological, and environmental factors on variations in fat deposition and distribution across populations.

Markers of inflammation (MOI) have been reported to influence bone health in adults, with reports of inverse associations. Adipose has also been linked to bone. In children, the interrelationships are unclear. The objective of this study was to evaluate the relationship between MOI (i.e. CRP, TNFR2, IL-6) and bone mineral content (BMC) and determine the contribution of fat deposition/distribution in children. Forty-nine children (59% male) 7-12 y participated. Body composition was evaluated by DXA, and MOI and insulin sensitivity (S(I)) were obtained during an IVGTT. Multiple linear regression was used for analyses. TNFR2 was inversely associated with BMC. In boys, TNFR2 was inversely associated with BMC, and in girls IL-6 was inversely associated with BMC, and total and percent fat influenced the relationships. Our results suggest a potential inhibitory role of inflammation on bone as well as a negative impact of adiposity. Future investigations are warranted to further investigate these relationships.

Overweight adolescents with type 2 diabetes have significantly higher lipoprotein abnormalities than those with type 1 diabetes.

AIM: Diabetes-associated glucoregulatory derangements may precipitate atherogenesis in childhood and CVD risk, particularly with obesity. We aimed to delineate lipoprotein profile differences between children with type 1 and 2 diabetes who are overweight/obese. METHODS: Data were obtained from electronic medical records of patients ≥85th BMI percentile with type 1 (n=159) and type 2 (n=77) diabetes, ages 12-19y. Group differences were evaluated by correlations and general linear modeling analysis, adjusting for BMI, HbA1c, and diabetes duration. RESULTS: There were no group differences in TC, LDL, or non-HDL. Fewer subjects with type 1 diabetes had low HDL (17 vs. 30%; P<0.05). While no difference in HbA1c level was observed between groups, HbA1c was positively correlated with TC (P≤0.0001), LDL (P≤0.0001), non-HDL (P≤0.0001), ApoB100 (P≤0.0001), and LDL pattern B (P≤0.0001). In adjusted models, apoB100 (85.4 vs. 91.3mg/dl; P<0.05) and incidence of LDL pattern B (21 vs. 42%; P<0.01) were lower in subjects with type 1 diabetes. BMI was inversely correlated with HDL, HDL-2 and HDL-3 (all P≤0.0001). The correlation of BMI with HDL-2 and HDL-3 were attenuated when evaluating subjects by diabetes type. CONCLUSIONS: Despite having no difference in absolute LDL levels, children with type 2 diabetes were more likely to have small, dense LDL particle pattern, higher apo B100 and lower total HDL, HDL-2, and HDL-3 fractions. Furthermore, poor glycemic control was associated with abnormal lipoprotein profiles in patients with both type 1 and 2 diabetes.

Pediatric obesity prevention: From naïve examination of energy imbalance towards strategies that influence the competition for nutrient resources among tissues.

Current pediatric obesity interventions have collectively yielded relatively unsuccessful results. In this Field of Vision, we present plausible physiologic underpinnings fostering ineffectiveness of conventional strategies grounded in requisite induction of negative energy imbalance. Moreover, such recommendations exacerbate the underlying metabolic dysfunction by further limiting metabolic fuel availability, lowering energy expenditure, and increasing hunger (recapitulating the starvation response amid apparent nutritional adequacy) which precede and promote obesity during growth and development. The qualitative aspects of musculoskeletal system (i.e., endocrine response, muscle functional capacity) are likely to improve metabolic function and increase nutrient delivery and utilization. An intricate and complex system including multiple feedback mechanisms operates to homeostatically regulate energy balance and support optimal body composition trajectories and metabolic health, during growth and development. Thus, ignoring the interdependencies of regulatory growth processes initiates a nuanced understanding of energy regulation and thus misguided attempts at preventive strategies. Importantly, these gains are not dependent upon weight-loss, rather we suggest can be achieved through resistance training. Collectively, optimizing musculoskeletal health via resistance training elicits augmentation of competitive capacity across systems. Further, substantial gains can be achieved in skeletal muscle mass, strength, and functional capacity through resistance training in a relatively short period of time.

Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults.

INTRODUCTION: Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease. The underlying reason(s) for the rise accompanying cardiovascular health decline are unclear. Prior studies have shown that FGF23 concentrations are associated with markers of inflammation and insulin resistance but they have been limited by a focus on persons with chronic kidney disease (CKD) and lack of race and sex diversity. The objective of this study was to examine the associations of FGF23 and markers of inflammation, insulin resistance, and anthropometrics in a large cohort of community-dwelling adults. METHODS: Associations of FGF23 with markers of inflammation [interleukin-6 (IL-6), IL-10, high sensitivity-CRP (hsCRP)], insulin utilization [resistin, adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR)] and anthropometrics [BMI and waist circumference (WC)] were examined cross-sectionally in a 1,040 participants randomly selected from the Reason for Geographic and Racial Differences in Stroke (REGARDS) Study, a national study of black and white adults ≥45 years. Effect modification by race and CKD status was tested, and stratified models were analyzed accordingly. RESULTS: Median FGF23 concentration was 69.6 RU/ml (IQR: 53.2, 102.7). Higher quartiles of FGF23 were associated with higher mean concentrations of IL-6, IL-10, hsCRP and resistin (Ptrend<0.001 for all). There were no significant differences in HOMA-IR, adiponectin concentrations, BMI, or WC across FGF23 quartiles in the crude analyses. CKD significantly modified the relationships between FGF23 and inflammatory markers, HOMA-IR, BMI and WC (P ≤ 0.01 for all). In linear regression models adjusted for sociodemographic and clinical variables, FGF23 was positively associated with IL-6, hsCRP, IL-10, HOMA-IR, BMI and WC in individuals without CKD, but not among individuals with CKD. Additionally, FGF23 was positively associated with resistin irrespective of CKD status. CONCLUSIONS: Elevated FGF23 concentrations may be considered a biomarker for decline in metabolic function among individuals with normal kidney function.

Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals.

BACKGROUND: Circulating FGF21 levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating FGF21 in the absence of disease, as well as age-related differences in body composition that may contribute to FGF21 regulation across groups. OBJECTIVE: The objectives of this study were to assess FGF21 levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating FGF21. MATERIALS AND METHODS: We cross-sectionally analyzed serum concentrations of FGF21 in 184 healthy subjects aged 5-80y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5-12y, young adults: 20-29y, adults: 30-50y, older adults: 55-64y, elder adults: 65-80y) with FGF21 concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of FGF21. RESULTS: Incremental increases in FGF21 levels were observed across age groups (youngest to highest). Age group was positively associated with FGF21 level independent of body composition indices (age group variable: ß=0.25, 0.24, 0.24, 0.23, all P<0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By FGF21 tertile, age group was associated with FGF21 in the lowest tertile only (ß=13.1, 0.19, 0.18, all P≤0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD. CONCLUSIONS: Our findings in a healthy population display an age-related increase in serum FGF21, highlighting a potential age effect in response to metabolic demand over the lifecourse. FGF21 levels increase with age independently of body composition. At lower levels of FGF21, BMD, but not other body composition parameters, attenuates the association between FGF21 level and age, suggesting the metabolic demand of the skeleton may provide a link between FGF21 and energy metabolism.

The relationship between bioactive components in breast milk and bone mass in infants.

Human breast milk (HBM) contains numerous bioactive components, recently shown to be associated with growth and body composition in breastfed offspring. Reciprocity in adipogenic and osteogenic pathways suggests bone mass may also be influenced by these components. The association between bioactive components found in HBM and bone mineral content (BMC), to our knowledge, is unknown. The purpose of this proof-of-principle study was to evaluate the association between specific bioactive components in HBM in exclusively breastfed infants and skeletal health in the first 6 months of life and examine potential gender differences in these associations. Thirty-five mother-infant dyads were followed from 1 to 6 months. The contents of a single breast expression were used for analyses of bioactive components (insulin, glucose, leptin, interleukin-6 and tumor necrosis factor-α (TNFα), whereas BMC was evaluated by dual-energy X-ray absorptiometry. In the total sample, there was a positive association between TNFα and BMC at 1 (P=0.004) and 6 months (P=0.007). When stratified by sex, females exhibited a positive association between BMC and glucose and an inverse relationship between BMC and TNF-α at 1 month with TNF-α strengthening (P=0.006) at 6 months. In males, at 6 months a positive relationship between BMC and HBM glucose and an inverse relationship with HBM leptin were observed with no associations observed at 1 month. Although preliminary, the associations between bioactive components in HBM highlight the importance HBM has on bone accretion. It is critically important to identify factors in HBM that contribute to optimal bone health.

Associations between vascular health indices and serum total, free and bioavailable 25-hydroxyvitamin D in adolescents.

OBJECTIVE: The role of vitamin D in cardiovascular health remains debated as results have been inconsistent. Previous studies have not considered the bioavailability of 25-hydroxy vitamin D [25(OH)D]. Objectives of our study were to investigate the association between serum concentrations of total, free and bioavailable 25(OH)D and independent predictors of cardiovascular risk such as flow mediated dilatation (FMD) and augmentation index (AIx). DESIGN: This cross-sectional study included 47 post-menarchal, adolescent females [31 African American (AA) and 16 European American (EA)]. METHODS: AIx was standardized to a heart rate of 75 beats/min (AIx75). Free and bioavailable 25(OH)D concentrations were calculated from standard formulas. RESULTS AND CONCLUSIONS: Mean age of the participants was 15.8 ± 1.4 years and mean body mass index was 23.1 ± 4.0 kg/m2. Serum total 25(OH)D was not associated with FMD, but was positively associated with AIx75 in the adjusted model (rho = 0.4, P = 0.03). AIx75 was positively associated with bioavailable 25(OH)D (rho = 0.4, P = 0.004) and free 25(OH)D (rho = 0.4, P = 0.009) and the associations persisted after adjusting for covariates. In race-specific analyses, total, free and bioavailable 25(OH)D were strongly positively associated with AIx75 in AA (rho = 0.5, 0.4, 0.4, respectively), which persisted even after adjusting for covariates. Whereas in EA there was an inverse association between total 25(OH)D and AIx75 in EA (rho = -0.6), which attenuated after adjusting for covariates. CONCLUSION: Circulating total, free and bioavailable 25(OH)D were associated with arterial stiffness in adolescent girls, and these associations were race dependent. Notwithstanding, the implications of associations between vascular function indices and 25(OH)D remains unclear.

Subclinical Indication of Linkage Between Markers of Skeletal and Cardiovascular Properties.

Little is known about early coincidental changes in bone and vascular properties, particularly in the context of skeletal anabolism (puberty) versus relative equilibrium (young adulthood). We aimed to determine if subclinical markers of vascular function were associated with bone mineral content (BMC) and to evaluate the contribution of systemic factors in healthy females ages 14-42 years. Endothelial function was assessed by flow mediated dilatation (FMD), arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), blood pressure (BP) by sphygmomanometer, BMC by DXA, and systemic factors by fasting blood draw. General linear models controlled for age, race and height indicated a positive association between systolic BP (SBP) and BMC independent of systemic factors. When stratified by age using 19 years as a cut-point, there was an inverse relationship between AIx75 in adolescents with insulin (P<0.10) or inflammatory markers (P<0.10) in statistical models. Conversely, there was a positive relationship between BMC and both PWV and AIx75 in young adults (P<0.05). The link between bone and the vasculature may be life stage-dependent. In the context of a less dynamic microenvironment in young adult females, metabolic factors appear to moderate less of an effect of hemodynamic properties on the skeleton relative to adolescents.

Diabetes-related impairment in bone strength is established early in the life course.

AIM: To evaluate properties of bone quantity/quality using young non-obese Type 1 (T1D)-diabetic (NOD) prone and syngenic non-diabetic (NOD.scid) mice. METHODS: Quantitative bone assessment of tibia was conducted using dual-energy X-ray absorptiometry (DXA) for the evaluation of body mass, bone mineral content, body fat mass and lean mass. Qualitative assessment was accomplished by three-point breakage for assessment of force to failure and micro-computed tomography for evaluation of trabecular and cortical properties of bone. In addition, fasting blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and compare glucose homeostasis between the strains of mice. RESULTS: Our findings support a perturbation in the relationship between bone quantity, quality, and subsequently, the association between structure and strength. There were no differences in DXA-assessed body composition (body fat, % fat mass and lean mass) and bone composition (bone mineral content and bone mineral density) between strains. However, relative to NOD.scid, NOD mice had lower trabecular bone volume, relative trabecular bone volume, trabecular number and trabecular total material density (P < 0.05). Conversely, NOD mice had greater cortical total mean volume (P < 0.05). General linear models analysis adjusted for body weight revealed a significant contribution of T1D to bone health as early as 5 wk. CONCLUSION: It is well-established that diabetes is a significant risk factor for increased fractures, although the underlying mechanisms are not fully understood. Investigation of bone parameters encompassing strength and structure early in the life course will facilitate the elucidation of the pathogenesis of impaired bone integrity.

BMI but Not Race Contributes to Vitamin D-Parathyroid Hormone Axis in Peripubertal Girls.

Currently, there is widespread interest in establishing 25-hydroxy vitamin D (25OHD) level preventing a secondary elevation in parathyroid hormone (PTH). The aim of this study was to identify the 25OHD nadir resulting in a rise of PTH and to determine if this inflection point is weight- or race-specific during growth and development in peripubertal girls. A total of 104 normal (n = 61) and overweight (n = 43) African American (AA) and European American (EA) girls, 5 to 14 years of age, were included. Though AAs had lower 25OHD levels, there was no difference in PTH compared with EAs. A 25OHD concentration of 27.2 ng/mL (P < .01) was indicated to increase PTH in normal-weight girls, although a statistically significant level was not established in overweight girls. No race difference in inflection point was observed. These data suggest a potential influence of weight status on the 25OHD-PTH inflection point in peripubertal girls. Accordingly, on determination of 25OHD level reflecting optimal health, consideration of weight status appears to be important during this critical period of growth and development.

Metabolic subtypes and risk of mortality in normal weight, overweight, and obese individuals with CKD.

BACKGROUND AND OBJECTIVES: Higher body mass index (BMI) is paradoxically associated with lower mortality in persons with CKD, but whether cardiometabolic abnormalities modulate this association is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants with CKD from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (n=4374) were analyzed. The harmonized criteria for metabolic syndrome were used to define metabolic health, and participants were categorized into one of six mutually exclusive categories defined by combined measures of metabolic health (metabolically healthy, <3 criteria for metabolic syndrome; metabolically unhealthy, ≥3 criteria) and weight status (normal weight, BMI 18.5-24.9 kg/m(2); overweight, BMI 25-29.9 kg/m(2); obese, BMI ≥30 kg/m(2)). Cox models were used to estimate the hazard ratio (HR) of death as a function of each category. RESULTS: A total of 683 deaths were observed over a mean 4.5 years of follow-up. In analyses adjusted for age, race, sex, and geographic region of residence, compared with metabolically healthy normal weight persons, the HRs of mortality in metabolically healthy overweight and obese persons were 0.68 (95% confidence interval [95% CI], 0.53 to 0.87) and 0.71 (95% CI, 0.51 to 0.98), respectively, whereas there were no statistically significant differences in survival among metabolically unhealthy overweight or obese individuals. After further adjustment for lifestyle, clinical and laboratory factors including markers of kidney function, the HR of mortality remained lower in metabolically healthy overweight individuals compared with metabolically healthy normal weight individuals (HR, 0.74; 95% CI, 0.57 to 0.96). CONCLUSIONS: Metabolic abnormalities may attenuate the magnitude and strength of survival benefits associated with higher BMI in individuals with CKD.

Macronutrient intake influences the effect of 25-hydroxy-vitamin d status on metabolic syndrome outcomes in african american girls.

The objectives were to determine the effect of macronutrient modification on vitamin D status and if change in 25-hydroxy-vitamin D concentration influences components of metabolic syndrome in obese African American girls. Methods. Five-week intervention using reduced CHO (43% carbohydrate; 27% fat: SPEC) versus standard CHO (55% carbohydrate; 40% fat: STAN) eucaloric diet. Subjects were 28 obese African American females, aged 9-14 years. Dual energy X-ray absorptiometry and meal test were performed at baseline and five weeks. Results. Approximately 30% of girls had metabolic syndrome. Serum 25OHD increased in both groups at five weeks [STAN: 20.3 ± 1.1 to 22.4 ± 1.1 (P < 0.05) versus SPEC: 16.1 ± 1.0 to 16.8 ± 1.0 (P = 0.05)]. The STAN group, increased 25OHD concentration over five weeks (P < 0.05), which was positively related to triglycerides (P < 0.001) and inversely associated with total cholesterol (P < 0.001) and LDL (P < 0.001). The SPEC group, had increase in 25OHD (P = 0.05), which was positively related to fasting insulin (P < 0.001) and insulin sensitivity while inversely associated with fasting glucose (P < 0.05). The contribution of vitamin D status to metabolic syndrome parameters differs according to macronutrient intake. Improvement in 25OHD may improve fasting glucose, insulin sensitivity, and LDL; however, macronutrient intake warrants consideration.