Effects of long-term antiepileptic polytherapy on bone biochemical markers in ambulatory children and adolescents and possible benefits of vitamin D supplementation: a prospective interventional study.

PURPOSE: Our aim was to investigate any adverse effects of long-term polytherapy (VPA and add-on-therapy) on bone biochemical markers in ambulatory children and adolescents with epilepsy and the possible benefits of vitamin D supplementation on the same markers. METHODS: In this prospective interventional study, the levels of 25(OH)D and the bone turnover markers of CrossLaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were determined in forty-two ambulatory children with epilepsy on polytherapy (valproic acid + one or more other from levetiracetam, topiramate, lamotrigine, or rufinamide). The same markers were assessed after a year's supplementation of vitamin D (400 IU/d) and were compared with those of clinically healthy controls. The respective mean (±SD) ages were 11.9 ±â€¯4.6 and 11.4 ±â€¯4.4 yrs. RESULTS: The basal mean 25(OH)D levels in the patients did not differ from controls (23.9 ±â€¯11.5 vs 27.4 ±â€¯13.3 ng/ml), but increased significantly after the vitamin D intake (31.1 ±â€¯13.3 ng/ml, p < 0.01). In parallel, basal serum CTX levels were found to be significantly lower in the patients than controls (0.89 ±â€¯0.63 vs 1.22 ±â€¯0.58 ng/ml, p < 0.02), but not tALP. Osteoprotegerin was higher in the patients (5.7 ±â€¯7.7 pmol/L vs 2.6 ±â€¯1.0 pmol/L, p < 0.03), while sRANKL did not differ. After vitamin D, the CTX levels increased to comparable levels in controls (0.99 ±â€¯0.57 ng/ml), and those of OPG decreased to levels that did not differ from controls (4.9 ±â€¯5.1 pmol/L). The ratio of OPG/sRANKL was higher in patients than controls before treatment (0.030 ±â€¯0.045 vs 0.009 ±â€¯0.005, p < 0.03), but decreased (0.026 ±â€¯0.038) to comparable values in controls later. CONCLUSIONS: These findings imply a lower bone turnover in the young patients on long-term polytherapy (VPA and add-on-therapy), but after one year's vitamin D intake, bone biochemical markers improved.

Use of Vitamin D Bolus in Fortified Juice for Improving Vitamin D Status in Children with Cerebral Palsy.

Children with cerebral palsy (CP) are at risk of poor nutrition due to a number of factors. Feeding, eating, drinking, and swallowing (FEDS) problems are common in these children and may result in protein-calorie malnutrition usually accompanied by micronutrient deficiencies. Vitamin D is among the elements whose uptake is obstructed. Insufficient exposure to solar radiation in children and adolescents with CP adds to further decreasing serum vitamin D levels thus potentially affecting growth, bone density, and muscle function. Since maintaining long-term adherence to daily oral administration of vitamin D in this population is often difficult, bolus therapy by using vitamin D-fortified products could be an alternative way of effective and safe vitamin D intake. PURPOSE: Assessing the efficacy of administration of bolus vitamin D in fortified juice for increasing 25(OH)D levels in a group of 15 children with CP. RESULTS: The juice was well tolerated, and a significant increase in 25(OH)D levels was observed from 54.1 to 110.3 nmol/L (p < 0.0001) 4 weeks after the administration without any case of hypercalcemia. CONCLUSION: Bolus therapy with vitamin D3-fortified juice is well tolerated and effectively increases 25(OH)D levels in children with CP.

Use of Fortified Bread for Addressing Vitamin D Deficiency.

Vitamin D deficiency due to inadequate sun exposure and/or inadequate intake from food is very common worldwide, consisting a major public health problem. As prolonged exposure to ultraviolet radiation involves risks, food fortification of staple foods emerges as a favorable solution for addressing vitamin D deficiency. Bread is a suitable candidate for fortification as it is consumed often and is the main carbohydrate source in European countries.The purpose of this study was the evaluation of the bioavailability of vitamin D from a fortified Greek-type bread that was developed as a means for addressing vitamin D deficiency, by comparing the absorption curve of vitamin D in fortified bread in relation to that of plain vitamin supplementation. Two groups of clinically healthy volunteers consumed 25,000 international units (IU) of vitamin D3 (cholecalciferol) either in fortified bread (Group A) or in a plain supplement form (Group B). The baseline plasma concentrations of cholecalciferol were 8.1 ± 6.0 ng/mL and 6.8 ± 3.4 ng/mL in Groups A and B, respectively. After 12, 24, and 48 h, the concentrations of cholecalciferol in Group A were 16.7 ± 4.8, 15.3 ± 8.3 and 11.9 ± 6.0 ng/mL, respectively, and in Group B, 15.2 ± 3.3, 11.6 ± 2.4, and 9.6 ± 3.6 ng/mL, respectively. In both groups, the concentrations of cholecalciferol at 12 and 24 h were significantly higher than the baseline concentrations (p < 0.01). There were no statistically significant differences between the concentrations of cholecalciferol between Groups A and B, at each time point.Cholecalciferol is bioavailable from Greek-type fortified bread and bread could be used for addressing vitamin D deficiency.

Increased Body Mass Index (BMI) and Sunscreen Use Are Associated with Inadequate Vitamin D Status in Greek Adults in Winter : BMI, Sunscreen Use and Vitamin D Status in Greek Adults.

Vitamin D deficiency is common even in sunny countries like Greece, especially during winter and is associated with skeletal disorders and additionally with increased risk for chronic diseases and adipose metabolic diseases such as obesity and diabetes. The purpose of this pilot study was the determination of vitamin D status in Greek adults and the investigation of possible correlation with lifestyles and somatometric characteristics. The study was conducted during winter and included 36 members (20 women and 16 men) of a university community in central Greece (latitude 39.6° North). Their age was 36.2 ± 16.3 years, body mass index (BMI) 26.4 ± 4.8 (women 26.6 ± 5.6, men 26.3 ± 3.8), and waist circumference 85.7 ± 13.3 cm (women 81.5 ± 13.0, men 90.7 ± 12.4) (mean ± SD). Mean serum 25(OH)D concentration was 20.1 ± 7.3 ng/mL (women 19.7 ± 7.6, men 20.7 ± 7.1). More than half of the participants had 25(OH)D levels below the 20 ng/mL (50 nmol/L) threshold of deficiency. There was a significant negative association between the use of sunscreen during summer and serum 25(OH)D concentrations during winter and a significant positive association between physical exercise and serum 25(OH)D. Levels of 25(OH)D tended to decrease with increasing BMI in persons with a BMI over 25.0. There is a high prevalence of vitamin D insufficiency in Greek adults during winter. Serum 25(OH)D levels in winter are positively associated with exercise and negatively associated with high BMI and the use of sunscreen during summer.

Investigation of Autoimmune Disease in Children with Chronic Spontaneous Urticaria.

INTRODUCTION: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children. METHODS: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation. RESULTS: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected. CONCLUSION: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs.

Vitamin D supplementation and bone markers in ambulatory children on long-term valproic acid therapy. A prospective interventional study.

PURPOSE: Our aim was to investigate any adverse effects of long-term valproic acid (VPA) therapy on bone biochemical markers in ambulatory children and adolescents with epilepsy, and the possible benefits of vitamin D supplementation on the same markers. METHODS: In this single center, the prospective interventional study levels of 25-hydroxyvitamin D (25OHD) and the bone turnover indices of Crosslaps (CTX), total alkaline phosphatase (tALP), osteoprotegerin (OPG), and the receptor activator for nuclear factor kB (RANK) ligand (sRANKL) were assessed before and after one year of vitamin D intake (400 IU/d) and were compared with those of clinically healthy controls. Fifty-four ambulatory children with mean (±standard deviation [SD]) age 9.0 ±â€¯4.5 yrs on VPA (200-1200 mg/d) long-term monotherapy (mean: 3.2 ±â€¯2.6 yrs) were studied, before and after a year's vitamin D intake (400 IU/d). RESULTS: Nearly half of the cases were vitamin D insufficient/deficient with mean levels 23.1 ±â€¯12.8 vs 31.8 ±â€¯16.2 ng/mL of controls (p = 0.004) and after the year of vitamin D intake increased to 43.2 ±â€¯21.7 ng/mL (p < 0.0001). In parallel, serum CTX and tALP had a decreasing trend approaching control levels but OPG and sRANKL did not change and were not different from controls. However, after vitamin D intake, a positive correlation was seen between 25OHD and OPG but not before. CONCLUSIONS: The findings imply a higher bone turnover in the young patients on long-term VPA therapy that decreased after vitamin D intake.

Elevated 1-hour post-load plasma glucose identifies obese youth with abnormal glucose metabolism and an unfavourable inflammatory profile.

CONTEXT: Adults with plasma glucose levels at one hour (1h-GL) ≥8.6 mmol/L during an oral glucose tolerance test (OGTT) are at increased risk for type 2 diabetes mellitus and present an unfavourable cardiometabolic and inflammatory profile, but relevant data on children are scarce. OBJECTIVE: To investigate if elevated 1h-GL during OGTT in obese children and adolescents is associated with insulin resistance and specific pro-inflammatory biomarkers. RESEARCH DESIGN AND METHODS: The study group comprised 88 obese children who attended the Outpatient Pediatric Clinic of our Hospital between January and December 2016. Children were divided into two groups according to 1h-GL during an OGTT: group 1 (n = 57) consisted of those with 1h-GL <8.6 mmol/L and group 2 (n = 31) of those with 1h-GL ≥8.6 mmol/L. Arterial blood pressure, body mass index (BMI) and waist circumference (WC) z-scores were measured in all participants. Specific insulin resistance (IR) indices, that is HOMA-IR, Matsuda index and Cederholm insulin sensitivity index (ISI) were calculated. Further, pro-inflammatory biomarkers that have been correlated with obesity complications, namely adiponectin, leptin, visfatin and interleukin (IL)-6 together with lipid levels were measured in all participants. Logistic regression analysis was used. RESULTS: Children in group 2 had higher insulin (15.5 ± 6.4 vs 10.9 ± 4.8 µU/mL), HOMA-IR (3.41 ± 1.4 vs 2.34 ± 1.05) and lower Matsuda index [4.7 (3.1) vs 18.4 (17) median plus IQR] and Cederholm ISI (38 ± 6 vs 56 ± 11), than children in group 1 (all P < 0.001). They also had higher visfatin (15.4 ± 5.2 vs 10.1 ± 7 ng/mL), and IL-6 [12.5 (6.7) vs 4.8 (4.4) pg/mL], and lower adiponectin (5.9 ± 3.4 vs 11.8 ± 4.7 µg/mL) than children in group 1 (all P < 0.001). Logistic regression showed that these differences between the two groups were independent of age, sex, Tanner stage, BMI and WC z-scores. CONCLUSIONS: In obese children, 1h-GL ≥8.6 mmol/L during an OGTT is correlated with worsened IR, and an unfavourable metabolic and inflammatory profile. Thus, 1h-GL could be used as an additional marker to identify obese children and adolescents at increased risk of developing obesity complications.

Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study.

BACKGROUND: A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. METHODS: A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3 months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (ß-Crosslaps) and the OPG and sRANKL levels were determined. RESULTS: No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The ß-Crosslaps and the ß-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). CONCLUSIONS: Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum ß-Crosslaps may reflect a beneficial response.

Comparative study of quantitative ultrasonography and dual-energy X-ray absorptiometry for evaluating renal osteodystrophy in children with chronic kidney disease.

Our aim was to assess bone parameters in children with chronic kidney disease (CKD) with both dual-energy X-ray absorptiometry (DXA) and quantitative ultrasonography (QUS) and additionally with biochemical markers of bone turnover. Twenty children (12 boys and 8 girls) with CKD and a mean decimal age of 9.47 ± 4.44 years were included in the study where anthropometric parameters (height and weight), pubertal status, bone mineral density (BMD) at lumbar spine, speed of sound (SOS) measured by QUS at radius and at tibia, and biochemical markers of bone metabolism were measured. Six patients (30%) had tibial SOS Z score <-1, and 52.7% had radial SOS Z score <-1, whereas only 16.67% had BMD Z score <-1. Patients had significantly increased levels of serum intact parathormone (p < 0.001), serum bone alkaline phosphatase (BAP) (p < 0.001) and serum N-terminal-mid fragment (aminoacids 1-43) of osteocalcin (p < 0.001) compared to controls, whereas serum osteoprotegerin was significantly decreased in patients compared to controls (p = 0.001). SOS was significantly correlated to BAP (r = -0.586, p = 0.013 and r = -0.709, p = 0.001, respectively, for radius and tibia). In conclusion no association between DXA and QUS measurements was documented in our study, whereas QUS was better correlated to biochemical indices of ROD.

Renal function and kidney length in preterm infants with nephrocalcinosis: a longitudinal study.

Renal injury in early life may lead to hypertension and renal disease in adulthood. In this prospective study, we estimated renal glomerular and tubular function and kidney length (KL) during the first 2 years of life of preterm infants with nephrocalcinosis (NC) associated with prematurity. The study cohort comprised 107 preterm children, 63 with NC and 44 control subjects without NC who were matched for gender, gestational age and birth weight. Kidney function was estimated based on measurements of serum creatinine (Scr), estimated glomerular filtration rate (eGFR), fractional excretion (FE) of sodium (Na), potassium (K), phosphate (P), magnesium (Mg) and uric acid (UA) and on the ratios of urinary Ca, oxalate (UOx) and citrate (UCit) to urinary creatinine (UCa/Ucr, UOx/Ucr and UCit/Ucr, respectively) calculated from morning urine collections. KL was measured by ultrasonography. Measurements were made at 40 weeks postmenstrual age and at 3, 6, 12 and 24 months of age. At 3 and 6 months, the NC group had higher UCa/Ucr, FEK and FEUA than the control group; at 12 months, only the UCa/Ucr and FEUA was still higher. The UCa/UCit ratio was higher in the NC group. Scr and eGFR did not differ between the groups at any time point. The NC group had a shorter KL up to 12 months of life (left kidney) or 24 months (right kidney). Based on these results, we conclude that NC in the preterm infants enrolled in our study was associated with impaired renal tubular function and a shorter KL in the first year of life.

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease.

Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3-4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3-4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (ß = 0.297, p < 0.01) and FGF-23 (ß = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (ß = -0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (ß = 0.368, p < 0.05) or iPTH (ß = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.

Inorganic phosphorus homeostasis during the first hour of dialysis.

BACKGROUND/AIM: Hyperphosphatemia is a well-recognized complication of chronic kidney disease, and phosphorus kinetics during hemodialysis (HD) remains a vague area of investigation. We studied the inorganic phosphorus homeostasis during the first hour of an HD session. MATERIALS/METHODS: Twelve patients were studied twice, in two consecutive HD sessions. Total (TPR), extracellular (EPR), and intracellular (IPR) phosphorus mass removal was determined using the direct dialysate quantification (DDQ) method. Alterations of serum inorganic phosphorus (sP), erythrocyte intracellular phosphorus (P(ERY)), and 2,3-diphosphoglycerate (2,3-DPG) concentrations were measured before HD initiation and at 1, 2, 3, 4, 5, 10, 30, and 60 min. RESULTS: The contribution of IPR to TPR was negative in the first 10 min of both HD sessions (-27.2 ± 6.5 and -26.4 ± 58 mmol, respectively, p = ns) while the contribution of the IPR to TPR increased as the time elapsed. Intracellular phosphorus and 2,3-DPG remained almost unchanged during the 60 min of HD session. CONCLUSIONS: Unchanged P(ERY) concentration during the first hour of an HD session does not reject the hypothesis of a simultaneous efflux and influx of phosphorus from/to intracellular compartment.

Serum adipocytokine and vascular inflammation marker levels in Beta-thalassaemia major patients.

BACKGROUND/AIM: The adipocytokines leptin and adiponectin represent a critical link between metabolism, immunity and chronic inflammation. A chronic vascular inflammatory state plays an important role in the pathophysiology of thalassaemia. We aimed to analyze the levels of these adipocytokines and determine any possible correlations with disease severity or vascular inflammation markers in beta-thalassaemia. METHODS: Serum leptin, adiponectin, high-sensitivity C-reactive protein, endothelins, vascular adhesion molecule-1, intracellular adhesion molecule-1 and L- and E-selectin were measured in 28 beta-thalassaemia patients and compared with levels in healthy controls. RESULTS: Leptin was significantly lower in patients compared to controls (2.23 ± 1.8 vs. 10.24 ± 5.78 µg/l; p = 0.0018), whereas adiponectin was elevated (11.75 ± 5.67 vs. 6.83 ± 2.75 µg/l; p = 0.009). For both adipocytokines, no correlations were found with characteristics such as age, gender, type of chelation, body mass index z score or haemoglobin. Leptin, but not adiponectin, was negatively correlated with ferritin (p = 0.032, r = -0.61). No correlations were found between leptin and the inflammation markers. However, adiponectin was positively correlated with endothelin-1 (p = 0.022, r = 0.63). CONCLUSIONS: Serum leptin is low in beta-thalassaemia, perhaps due to the toxic effect of iron overload on adipose tissue. Paradoxically, adiponectin levels are high and positively correlated with endothelin-1, raising questions about the pro- or anti-inflammatory role of this adipocytokine in beta-thalassaemia.

Vitamin D status and cardiometabolic risk factors in Greek adolescents with obesity - the effect of vitamin D supplementation: a pilot study.

INTRODUCTION: Obesity is associated with cardiovascular disease (CVD) risk factors as well as decreased 25(OH) vitamin D serum levels. We aimed to study 25(OH) vitamin D levels in adolescents with obesity compared with normal weight controls in association with CVD risk factors, and the possible effect of vitamin D supplementation. MATERIAL AND METHODS: In a cross-sectional study, 69 obese and 34 normal-weight adolescents were included. In an interventional study 15 adolescents with obesity and vitamin D insufficiency were given 2000 IU vitamin D per os daily for 3 months. RESULTS: Adolescents with obesity had significantly lower 25(OH) vitamin D levels compared with normal-weight controls (12.0 (3.0-36.0) vs. 34.0 (10.0-69.0) ng/ml, respectively, p < 0.001). In adolescents with obesity, 25(OH) vitamin D was inversely associated with leptin even after adjustment for body mass index (BMI) (r = -0.340, p = 0.009). Conversely, 25(OH) vitamin D was not related with other parameters, such as BMI, blood pressure, lipids, glucose, insulin, homeostasis model assessment (HOMA) index, adiponectin, leptin/adiponectin ratio, and visfatin levels. Following supplementation in 15 vitamin D insufficient adolescents with obesity, 25(OH) vitamin D significantly increased (from 17.3 (12.5-27.8) to 32.6 (14.3-68.0) ng/ml, p = 0.005) and so did low-density lipoprotein cholesterol (LDL-C) (from 85.4 ±9.5 to 92.1 ±15.8 mg/dl, p = 0.022), while there were reductions in glycated haemoglobin (HbA1c) (from 5.8 ±0.2 to 5.5 ±0.1%, p = 0.03) and leptin (from 19.7 (7.8-45.5) to 15.1 (4.3-37.3) ng/ml, p = 0.03). Oxidised LDL, paraoxonase, arylesterase, and urine isoprostanes remained unchanged. CONCLUSIONS: Adolescents with obesity had lower 25(OH) vitamin D, which may be associated with higher leptin levels. Vitamin D supplementation may lead to HbA1c and leptin reductions, but also to an increase in LDL-C.

The association between vitamin D status and infectious diseases of the respiratory system in infancy and childhood.

PURPOSE: Respiratory tract infections (RTIs) are a major cause of illness worldwide and the most common cause of hospitalization for pneumonia and bronchiolitis. These two diseases are the leading causes of morbidity and mortality among children under 5 years of age. Vitamin D is believed to have immunomodulatory effects on the innate and adaptive immune systems by modulating the expression of antimicrobial peptides, like cathelicidin, in response to both viral and bacterial stimuli. The aim of this review is to summarize the more recently published data with regard to potential associations of 25-hydroxyvitamin D [25(OH)D] with infectious respiratory tract diseases of childhood and the possible health benefits from vitamin D supplementation. METHODS: The literature search was conducted by using the PubMed, Scopus, and Google Scholar databases, with the following keywords: vitamin D, respiratory tract infection, tuberculosis, influenza, infancy, and childhood. RESULTS: Several studies have identified links between inadequate 25(OH)D concentrations and the development of upper or lower respiratory tract infections in infants and young children. Some of them also suggest that intervention with vitamin D supplements could decrease both child morbidity and mortality from such causes. CONCLUSIONS: Most studies agree in that decreased vitamin D concentrations are prevalent among most infants and children with RTIs. Also, normal to high-serum 25(OH)D appears to have some beneficial influence on the incidence and severity of some, but not all, types of these infections. However, studies with vitamin D supplementation revealed conflicting results as to whether supplementation may be of benefit, and at what doses.

Effect of combined vitamin D administration plus dietary intervention on oxidative stress markers in patients with metabolic syndrome: A pilot randomized study.

BACKGROUND: Metabolic syndrome (MetS) patients can have low 25-hydroxyvitamin D 25(OH)VitD levels, which may be associated with increased oxidative stress. There is little data on the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in these patients. AIM: To study the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in MetS patients. METHODS: This is a pre-specified analysis of a previously published study (NCT01237769 ClinicalTrials.gov). MetS participants (n = 50, 52 ± 10 years) were given dietary instructions and were randomized to 25(OH)VitD 2.000 IU/day p.o. (Suppl group) or no supplementation (No-Suppl group). Serum 25(OH)VitD, oxidized LDL (ox-LDL), paraoxonase activity (PON-1), arylesterase activity (ARYL) and urine 8-isoprostane (8-iso-PGF2a) levels were measured at baseline and after 3 months. RESULTS: MetS patients had low baseline 25(OH)VitD levels, which increased by 90% in the Suppl group [from 16.1 (3.3-35.1) to 30.6 (8.4-67.6) ng/mL, p = 0.001] and by 33.3% in the No-Suppl group [from 9.9 (4.0-39.6) to 13.2 (3.5-36.8) ng/mL, p = NS] after intervention. Ox-LDL, PON-1 and ARYL did not change significantly at follow-up in both groups, except for urine 8-iso-PGF2a levels that decreased by 22.7% in the Suppl group [from 48.8 (26.8-137.1) to 37.7 (12.3-99.0) ng/mmol creatinine, p = 0.015] and by 14.4% in No-Suppl group [from 45.8 (16.6-99.3) to 39.2 (13.3-120.1) ng/mmol creatinine, p = NS]. The reduction in 8-iso-PGF2a levels did not differ significantly between the 2 groups. CONCLUSION: The administration of 25(OH)VitD plus dietary intervention in patients with MetS was not associated with meaningful reductions in oxidative stress markers compared with dietary intervention alone.

Serum vitamin D in obese and overweight subjects according to estimated glomerular filtration rate.

OBJECTIVE: Obesity and renal disease are both associated with low serum 25(OH)D. The aims of the present study were to (a) assess vitamin D status and compare serum vitamin D levels in overweight/obese versus normal-weight individuals according to eGFR and (b) assess the role of 25(OH)D in the development of secondary hyperparathyroidism (SHPT). DESIGN: Serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), calcium, and phosphate were measured in 104 subjects with BMI > 25 kg/m2. Participants were categorized according to eGFR (ml/min/1.73m2): G1 ≥ 60 (n = 53), G2 30-59 (n = 35), and G3 15-29 (n = 16). Fifty normal-weight individuals with comparable eGFR served as controls: G1-nw (n = 23), G2-nw (n = 18), and G3-nw (n = 9). RESULTS: 25(OH)D levels were lower in G1 compared to those in G1-nw (21.7 ± 6.5 vs 26.5 ± 7.0 ng/ml, p = 0.005), G2 versus G2-nw (19.0 ± 6.0 vs 25.0 ± 5.2 ng/ml, p = 0.001), and G3 vs G3-nw (15.8 ± 4.7 vs 20.3 ± 4.5 ng/ml, p = 0.030). 1,25(OH)2D and PTH levels were similar in obese/overweight versus normal-weight individuals in each of the eGFR categories. Factors independently associated with low 25(OH)D levels were BMI > 25 kg/m2, lower eGFR, and female gender. Mean 25(OH)D levels were < 30 ng/ml in both overweight and controls, in all eGFR groups. SHPT was universally observed when eGFR was < 30 ml/min/1.73m2. CONCLUSIONS: Lower serum 25(OH)D but similar 1,25(OH)2D and PTH levels were observed in overweight/obese compared to normal-weight individuals. Even though vitamin D insufficiency was common across all eGFR categories, secondary hyperparathyroidism was more prevalent as eGFR declined.

Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth.

OBJECTIVE: Insulin resistance has been linked to intrauterine growth retardation (IUGR); adiponectin is a protein with insulin-sensitizing properties. This study was designed to test whether being born small for gestational age (SGA) has an effect on blood levels of adiponectin and leptin, insulin resistance parameters, and lipid profile in pre-puberty, taking into consideration the severity of IUGR. METHODS: Serum levels of adiponectin, leptin, total cholesterol (t-CHOL), high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, apolipoproteins A-1 (Apo A-1), Apo B and Apo E, lipoprotein(a) (Lp(a)), fasting glucose, and insulin (Ins), the homeostasis model assessment insulin resistance index (HOMA-IR) and anthropometric indices were evaluated in 70 children aged 6-8 years, born appropriate for gestational age (AGA; n = 35) and SGA (n = 35), matched for age, gender, height, and BMI. SGA children were divided into two subgroups according to the severity of IUGR: SGA<3rd percentile (n = 20), and SGA 3rd-10th percentile (n = 15). They were also subdivided in two subgroups, those with (n = 25) and those without (n = 10) catch-up growth, considering their actual height corrected for mid-parental height. RESULTS: SGA children had higher Ins and HOMA-IR than AGA children (Ins, 42 +/- 23 vs 32 +/- 11 pmol/l; HOMA-IR, 1.30 +/- 0.8 vs 0.92 +/- 0.3; P<0.05). No significant difference in serum leptin was found between the SGA and the AGA groups but adiponectin showed a trend to be higher in SGA children (13.6 +/- 5.7 vs 10.8 +/- 5.9 microg/ml respectively). SGA children without catch-up growth had higher adiponectin (15.6 +/- 8.5 microg/ml, P<0.05) than AGA children. Among the SGA children, the subgroup <3rd percentile had higher Lp(a) than the subgroup 3rd-10th percentile (P<0.05). An independent positive correlation between adiponectin and Lp(a) was observed in SGA children (R = 0.59, P<0.01). CONCLUSION: SGA children, although more insulin resistant, had similar or higher adiponectin levels than matched AGA children in pre-puberty. The severity of IUGR appears to affect their metabolic profile during childhood.

No effect of vitamin D supplementation on cardiovascular risk factors in subjects with metabolic syndrome: a pilot randomised study.

INTRODUCTION: Patients with metabolic syndrome (MetS) may have lower 25-hydroxyvitamin D (25(OH)VitD) serum levels compared with non-MetS individuals. Vitamin D (VitD) deficiency is associated with various cardiovascular disease (CVD) risk factors. Yet, the effect of VitD supplementation on MetS remains uncertain. Our aim was to examine the effect of VitD supplementation on CVD risk factors in MetS subjects. MATERIAL AND METHODS: This pilot study had a PROBE (prospective, randomised, open-label, blinded end-point) design. Fifty patients with MetS were included and randomised either to dietary instructions (n = 25) (control group) or dietary instructions plus VitD 2000 IU/day (n = 25) (VitD group) for 3 months. This study is registered in ClinicalTrials.gov (NCT01237769). RESULTS: In both groups a similar small weight reduction was achieved. In the VitD group serum 25(OH)VitD levels significantly increased by 91% (from 16.0 (3.0-35.0) to 30.6 (8.4-67.0) ng/ml, p < 0.001), while in the control group no significant change was observed (from 10.0 (4.0-39.6) to 13.0 (3.5-37.0) ng/ml). In both groups triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, haemoglobin A1c, homeostasis model assessment index and diastolic blood pressure did not significantly change. Systolic blood pressure decreased by 3.7% (from 134 ±14 to 129 ±13 mm Hg, p = 0.05) in the VitD group, while it decreased by 1.5% (from 132 ±13 to 130 ±16 mm Hg, p = NS) in the control group (p = NS between groups). In the VitD group serum 25(OH)VitD increase was negatively correlated with SBP decrease (r = -0.398, p = 0.049). CONCLUSIONS: VitD supplementation (2000 IU/day) did not affect various CVD risk factors in patients with MetS.