Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity.

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14-18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

Pulmonary function changes in older adults with and without metabolic syndrome.

The low-grade inflammation associated with metabolic syndrome (MS) triggers functional and structural alterations in several organs. Whereas lung function impairment is well reported for older adult population, the effect of MS on functional and immunological responses in the lungs remains unclear. In this cross-sectional study we determined whether MS alters pulmonary function, and immunological responses in older adults with MS. The study sample consisted of older adults with MS (68 ± 3 years old; n = 77) and without MS (67 ± 3 years old; n = 77). Impulse oscillometry was used to evaluate airway and tissue resistance, and reactance. Biomarkers of inflammation and fibrosis were assessed in the blood and in breath condensate. The total resistance of the respiratory system (R5Hz; p < 0.009), and the resistance of the proximal (R20Hz; p < 0.001) and distal (R5Hz-R20Hz; p < 0.004) airways were higher in MS individuals compared to those without MS. Pro-inflammatory (leptin, IL-1beta, IL-8, p < 0.001; TNF-alpha, p < 0.04) and anti-inflammatory cytokines (adiponectin, IL-1ra, IL-10, p < 0.001), anti-fibrotic (relaxin 1, relaxin 3, Klotho, p < 0.001) and pro-fibrotic (VEGF, p < 0.001) factors were increased in sera and in breath condensate individuals with MS. The results show that MS adversely affect lung mechanics, function, and immunological response in older adults. The data offer a metabolic basis for the inflammaging of the lungs and suggest the lungs as a potential therapeutic target for controlling the immune response and delaying the onset of impaired lung function in older adults with MS.

Branched-chain Amino Acids and Relationship With Inflammation in Youth With Obesity: A Randomized Controlled Intervention Study.

CONTEXT: Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. OBJECTIVE: We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). METHODS: Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. RESULTS: Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P < 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P < 0.05). The PAL-I produced only negligible effects (P > 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P < 0.05). CONCLUSION: The novel finding of the BCAA-inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.

Durability of Changes in Biomarkers of Cardiometabolic Disease: 1-Year Family-Based Intervention in Children with Obesity.

Background: The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Methods: Children with an age-adjusted body mass index (BMI) percentile ≥85 (N = 130; age 8-11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Results: Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 (P < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen (P < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits (P < 0.05) from the 6- to 12-month follow-up. Conclusions: The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).

Fish Oil Supplementation in Overweight/Obese Patients with Uncontrolled Asthma. A Randomized Trial.

Rationale: Omega-3 fatty acid (n3PUFA) supplementation has been proposed as a promising antiasthma strategy. The rs59439148 ALOX5 polymorphism affects leukotriene production and possibly inflammatory responses to n3PUFA. Objectives: Assess the effects of n3PUFA supplementation and ALOX5 genotype on asthma control in patients with obesity and uncontrolled asthma. Methods: This multicenter trial among 12- to 25-year-olds with overweight/obesity and uncontrolled asthma randomized subjects in a 3:1 allotment to n3PUFA (4 g/d) or soy oil control for 24 weeks. Asthma Control Questionnaire was the primary outcome; secondary outcomes included blood leukocyte n3PUFA levels, urinary leukotriene-E4, spirometry, and asthma-related events. The number of SP1 tandem repeats in rs59439148 determined ALOX5 genotype status. Simple and multivariable generalized linear models assessed effects on outcomes. Results: Ninety-eight participants were randomized (77 to PUFA, 21 to control), and more than 86% completed all visits. Asthma and demographic characteristics were similar among treatment groups. n3PUFA treatment increased the n3-to-n6 PUFA ratio in circulating granulocytes (P = 0.029) and monocytes (P = 0.004) but did not affect mean Asthma Control Questionnaire change at 6 months (n3PUFA: mean, -0.09; 95% confidence interval [CI], 0.09 to 0.10; vs. control: mean, -0.18; 95% CI, -0.42 to 0.06; P = 0.58). Changes in urinary leukotriene-E4 (P = 0.24), forced expiratory volume in 1 second % predicted (P = 0.88), and exacerbations (relative risk [RR], 0.92; 95% CI, 0.30-2.89) at 6 months were similar in both groups. n3PUFA treatment was associated with reduced asthma-related phone contacts (RR, 0.34; 95% CI, 0.13-0.86; P = 0.02). ALOX5 genotype did not affect n3PUFA treatment responses. Conclusions: We did not find evidence that n3PUFA use improves most asthma-related outcomes and cannot recommend it as a prevention strategy for overweight/obese patients with asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01027143).

Roux-en-Y gastric bypass surgery in youth with severe obesity: 1-year longitudinal changes in spexin.

BACKGROUND: Spexin is a novel peptide predominantly produced in human white adipose tissue and has recently been implicated as a potential signal in the regulation of body weight, energy homeostasis, and satiety. The effect of bariatric surgery on spexin is unknown. OBJECTIVES: To study the effect of Roux-en-Y gastric bypass (RYGB) surgery on endogenous spexin concentration and various risk factors of type 2 diabetes and cardiovascular disease in youth with severe obesity. SETTING: University hospital, United States METHODS: Spexin, body mass index (BMI), insulin, glucose, total and high molecular weight adiponectin, leptin, and high sensitivity C- reactive protein were measured longitudinally (baseline, 6 mo, and 12 mo) after RYGB surgery in girls with severe obesity (n = 12; age = 16.7 ± 1.5 years; BMI = 51.6 ± 2.9 kg/m2). RESULTS: Serum spexin concentration increased (P = .01) at 6 months after surgery and stabilized afterward. Spexin level correlated negatively with homeostatic model assessment insulin resistance, HOMA-IR (Spearman correlation r = -.796, P < .001) and positively with high molecular weight adiponectin (Spearman correlation r = .691, P = .011). The change in spexin concentration, from baseline to 6 months after surgery, was inversely correlated with the corresponding change in BMI (Spearman correlation r = -.573, P = .051). Furthermore, the 6-month changes in spexin and HOMA-IR were inversely correlated (slope [standard error, SE] = -.0084 (.0019), P = .001)], even after adjusting for the change in BMI. CONCLUSIONS: The enhancement of circulating spexin concentration in response to RYGB and correlations with beneficial postoperative changes in various adipokines in youth are novel findings that require further validation.

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents.

BACKGROUND: The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues. METHODS: We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment. RESULTS: 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05). CONCLUSIONS: The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.

Self-initiated physical activity is associated with high sensitivity C-reactive protein: A longitudinal study in 5,030 adults.

BACKGROUND AND AIMS: Structured regular exercise programs decrease high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation in adults. Longitudinal effects of self-initiated physical activity levels (PAL) on hsCRP are less clear. This study evaluated the association of longitudinal changes in hsCRP in relation to modifications in PAL, over time, in a large sample of adults. METHODS: Participants included 5030 adults, 4045 (80%) males, undergoing routine health screening examinations. Elevated level of hsCRP was defined as ≥3 mg/L. Self-reported PAL, height, weight, blood pressure and blood samples were collected at baseline and after a median of 2.9 years (P25th 1.97 and P75th 4.37 yrs). Participants were stratified according to their PAL at baseline and follow-up as: i) persistently physically inactive; ii) became physically inactive; iii) became physically active; iv) persistently physically active (active both at baseline and follow-up). RESULTS: Persistently physically active participants had lower odds of having higher hsCRP (OR = 0.35 [95% CI: 0.25 to 0.48]). The maintenance of high PAL was associated with lower hsCRP in both sexes (men: OR = 0.44 [0.30 to 0.65] and women: OR = 0.35 [0.16 to 0.76]). Participants with overweight/obesity (OR = 0.43 [95% CI: 0.29 to 0.63]) and smokers (OR = 0.123 [95% CI: 0.03 to 0.60]) who were persistently active had lower odds of having higher hsCRP compared to physically inactive peers. CONCLUSIONS: Self-initiated PAL was longitudinally associated with hsCRP in adults. The data suggest that the initiation or maintenance of PA attenuates the low-grade inflammatory state, independent of sex, body weight and smoking status.

Effect of parathyroidectomy on osteopontin and undercarboxylated osteocalcin in patients with primary hyperparathyroidism.

PURPOSE: Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with ß-carboxyl-terminal cross-linking telopeptide of type 1 collagen (ß-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT. METHODS: We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy. Circulating levels of OC, ucOC, OPN, ß-CTX, and OPG were examined as bone biomarkers along with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25-hydroxyvitamin D, creatinine, and demographics. RESULTS: Participants (27 females/3 males) were 60 ± 9 (mean±SD) years old. There was a significant reduction of ucOC (7.9 ± 5.1 [median±SIQR] vs. 6.6 ± 3.7 ng/mL, p = 0.022) and OPN (75.4 ± 14.5 vs. 54.5 ± 9.2 ng/mL, p < 0.001) pre- versus post-parathyroidectomy. There were no univariate differences postoperatively for IL-6, HOMA-IR, leptin, or adiponectin. Regression analysis showed that postoperative levels of adiponectin, IL-6, and OPN were significantly associated with ucOC, while adjusting for PTH and albumin corrected calcium levels (model R2 = 0.610, p = 0.001). With OPN as the dependent variable, higher adiponectin and lower ucOC were significantly associated with lower OPN levels postoperatively (model R2 = 0.505, p = 0.010). CONCLUSION: The lower 1-month postoperative OPN and ucOC levels in PHPT seem to indicate reduced bone resorption. Decreased ucOC levels may also suggest lower energy demands postoperatively.

Physical activity levels and hepatic steatosis: A longitudinal follow-up study in adults.

BACKGROUND AND AIM: This study aimed to evaluate the impact of physical activity (PA) on the course of hepatic steatosis (HS) in adults. METHODS: Hepatic steatosis status (ultrasonography) and PA levels were evaluated in 5860 subjects at baseline and after approximately 2.5 years (range: 19-50 months). At follow up, possible exposures to different PA levels were those who remained inactive, became inactive, became active, and remained active. After follow up, subjects were then classified according to the four possible states (outcomes): "remained without HS," "developed HS" (subjects without HS at baseline), "remained with HS," or "reverted HS." RESULTS: After multivariate adjustments, individuals without HS that became or remained physically active were less likely to develop HS compared with those who remained physically inactive (odds ratio = 0.75, P = 0.04 and 0.75, P = 0.03, respectively). Among those with HS at baseline, becoming and remaining physically active beneficially improved the HS status (odds ratio = 0.64, P = 0.01 and 0.66, P = 0.01, respectively). However, the significance was lost when adjusted for changes in body mass index. CONCLUSION: Higher levels of PA were associated with prevention and treatment of HS, with evidence of effect mediation by changes in body mass index.

Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study.

PURPOSE: To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. METHODS: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m-2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. RESULTS: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL-1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL-1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL-1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL-1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL-1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. CONCLUSIONS: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.

Pre-heparin lipoprotein lipase mass as a potential mediator in the association between adiponectin and HDL-cholesterol in type 2 diabetes.

AIM: Lipoprotein lipase (LPL) is a major enzyme in lipid metabolism. Dyslipidemia, characterized by decreased high-density lipoprotein cholesterol (HDL-C), is prevalent in persons with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether pre-heparin LPL mass mediates the association between adiponectin and HDL-C in individuals with T2DM. METHODS: Pre-heparin LPL mass was measured via an enzyme-linked immunosorbent assay, adiponectin by radioimmunoassay, and HDL-C was determined enzymatically. Participants' (n = 50) demographics, HbA1c, adiposity, homeostasis model assessment for insulin resistance (HOMA-IR), serum creatinine, and lipids were measured. Path analysis was utilized to test whether pre-heparin LPL mass is a mediator in the relationship between adiponectin and HDL-C. RESULTS: All four criteria for mediation were satisfied in the path analysis. The indirect effect of adiponectin on HDL-C through pre-heparin LPL mass was significant, p = 0.001, whereas the direct effect of adiponectin on HDL-C was not significant, p = 0.074. These results remained consistent even after adjustments for age, gender, body mass index, HOMA-IR, and serum creatinine in the model. CONCLUSION: The findings in this study suggest that pre-heparin LPL mass may mediate the association between adiponectin and HDL-C in T2DM. This relationship for measures of HDL-C functionality requires future investigation.

Effects of Mixed Carotenoids on Adipokines and Abdominal Adiposity in Children: A Pilot Study.

Context: Carotenoids have been implicated in the regulation of adipocyte metabolism. Objective: To compare the effects of mixed-carotenoid supplementation (MCS) versus placebo on adipokines and the accrual of abdominal adiposity in children with obesity. Design and Setting: Randomized (1:1), double-blind, placebo-controlled intervention trial to evaluate the effects of MCS over 6 months in a subspecialty clinic. Participants: Twenty (6 male and 14 female) children with simple obesity [body mass index (BMI) > 90%], a mean age (± standard deviation) of 10.5 ± 0.4 years, and Tanner stage I to V were enrolled; 17 participants completed the trial. Intervention: MCS (which contains ß-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin, and γ-tocopherol) or placebo was administered daily. Main Outcome Measures: Primary outcomes were change in ß-carotene, abdominal fat accrual (according to magnetic resonance imaging), and BMI z-score; secondary outcomes were adipokines and markers of insulin resistance. Results: Cross-sectional analysis of ß-carotene showed inverse correlation with BMI z-score, waist-to-height ratio, visceral adipose tissue, and subcutaneous adipose tissue (SAT) at baseline. MCS increased ß-carotene, total adiponectin, and high-molecular-weight adiponectin compared with placebo. MCS led to a greater reduction in BMI z-score, waist-to-height ratio, and SAT compared with placebo. The percentage change in ß-carotene directly correlated with the percentage change in SAT. Conclusions: The decrease in BMI z-score, waist-to-height ratio, and SAT and the concomitant increase in the concentration of ß-carotene and high-molecular-weight adiponectin by MCS suggest the putative beneficial role of MCS in children with obesity.

Decreased Circulating Levels of Spexin in Obese Children.

CONTEXT: Spexin is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in children. OBJECTIVE: The aim of the current study was to determine the potential role of Spexin in obese children and explore its relationships with various cardiometabolic risk factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study composed of 69 children (51 obese and 18 normal weight; age 15.3 ± 0.26 y). OUTCOME MEASURES: Spexin was measured using a specific enzyme-linked immunosorbent assay. Leptin, total and high-molecular-weight adiponectin, IL-6, high-sensitivity C-reactive protein, glucose, and insulin were also measured. Mann-Whitney U test, Pearson and Spearman rank correlations, logistic regression, and cluster analysis were used for the analysis and interpretation of the data. RESULTS: Spexin levels were significantly lower in obese vs normal-weight children, median(IQR) (0.33 ng/mL [0.27-0.44] vs 0.42 ng/mL [0.33-0.55]; P = .024), but did not correlate with other adipokines and/or insulin and glucose levels. Ordinal categorical variables of Spexin showed a strictly reverse association of obesity with the level of Spexin. Cluster analysis of Spexin and body mass index z score resulted in splitting the participants into normal-weight and obese-weight groups with high accuracy. CONCLUSIONS: Lower circulating levels of Spexin in obese children compared with their normal-weight counterparts and the ability to discriminate obese and normal-weight groups based on Spexin concentration enabled us to suggest a potential role for this novel peptide in childhood obesity. The clinical significance of these findings needs additional investigation.

Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function.

AIMS: Osteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM). METHODS: RR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants' demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined. RESULTS: Using stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age×25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R2=0.598, p<0.001; E/I model R2=0.594, p<0.001). CONCLUSION: Our results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.

Effect of vitamin D3 treatment on endothelial function in obese adolescents.

BACKGROUND: Obesity in children is associated with vitamin D deficiency and endothelial dysfunction. It is not known if treatment with vitamin D improves endothelial function in obese adolescents. OBJECTIVE: This study aimed to determine whether treatment with vitamin D3 improves endothelial function in obese adolescents. METHODS: Nineteen obese adolescents, 13-18 years of age, with 25-hydroxy vitamin D (25[OH]D) levels <75 nmol L(-1) were treated with 100 000 IU vitamin D3 orally once a month for 3 months in an open-label, single-centre prospective trial. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at study entry and 1 month after the third dose of vitamin D3 . Biochemical parameters, including calcium, fasting lipids, glucose, insulin and high-sensitivity C-reactive protein, were also obtained. RESULTS: Mean 25(OH)D levels increased from 55.9 ± 12.2 to 86.9 ± 16.7 nmol L(-1) (P < 0.01). There was no correlation between 25(OH)D levels and brachial artery FMD. The brachial artery FMD (%) did not change significantly following vitamin D3 treatment (9.5 ± 3.53 vs. 10.3 ± 3.83, P = 0.83). Serum parathyroid hormone declined from 3.8 ± 1.5 to 3.1 ± 1 pmol L(-1) (P = 0.01). The remainder of biochemical measurements did not show a significant change. CONCLUSIONS: Treatment with vitamin D3 , 100 000 IU once a month for 3 months was effective in increasing 25(OH)D levels in obese adolescents but did not impact endothelial function.