The relation of vitamin D status with metabolic syndrome in childhood and adolescence: an update.

Among children and adolescents, metabolic syndrome (MetS) is more common than previously believed. Hence, any information on the relation between vitamin D insufficiency/deficiency and insulin resistance (IR) in this population with risk of developing MetS is of great importance. This review analyzes and evaluates the existing evidence from cross-sectional, observational, and retrospective studies concerning the effect of vitamin D insufficiency/deficiency on MetS as a whole or on its various components. Most data show that insufficient vitamin D status is associated with increased prevalence of MetS or its individual components, mainly blood pressure and IR, often independent of overall obesity or abdominal adiposity. The implications of these findings could be associated with increased risk for developing cardiovascular disease and type 2 diabetes mellitus in later life. The very few randomized control trials examining any possible beneficial effects of vitamin D supplementation are also included.

Vitamin D, parathormone, and insulin resistance in children born large for gestational age.

BACKGROUND: Low vitamin D [25(OH)D] levels have been associated with type-2 diabetes mellitus. Children born large for gestational age (LGA) may exhibit increased indices of insulin resistance early in life. OBJECTIVE: This study aims to prospectively examine serum 25(OH)D and parathormone (iPTH) levels in LGA and appropriate for gestational age (AGA) prepubertal children, in relation to the severity of macrosomia and insulin resistance. METHODS: Children were examined at age 5-7.5 years, 38 born LGA and 39 AGA, matched for age, gender, body weight, height and body mass index (BMI). Twenty-one LGA had birth weights in the 90th-97th percentile and 17 >97th percentile. Fasting serum levels of glucose, insulin, 25(OH)D, and iPTH were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was estimated. RESULTS: The insulin resistance indices were higher in the LGA >97th percentile subgroup than in the AGA group: HOMA-IR 1.53±0.66 vs. 1.04±0.53 and fasting insulin 6.92±3.1 vs. 4.78±2.2 µIU/mL (but similar to the AGA group), and in the LGA 90th-97th percentile subgroup: HOMA-IR 1.17±0.61 and insulin 5.53±2.2. There was no difference in 25(OH)D among the three subgroups. The iPTH was higher in the LGA >97th percentile subgroup than in the AGA group (26.8±7.6 and 22.6±7.2 pg/mL, respectively, p<0.05), although it was not correlated with insulin resistance indices. Birth weight was correlated negatively with fasting insulin and HOMA-IR in the entire cohort, independent of age, sex, waist circumference, and BMI (ß=0.37, p<0.01 and ß=0.30, p<0.05, respectively), while waist circumference was positively correlated with HOMA-IR (R=0.40, p<0.001). CONCLUSION: Birth weight and current body composition appear to affect glucose homeostasis in LGA prepubertal children, while the serum levels of 25(OH)D and iPTH appear to be uninvolved.

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.

Prothrombotic state, cardiovascular, and metabolic syndrome risk factors in prepubertal children born large for gestational age.

OBJECTIVE: To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS: At 6-7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS: LGA children had higher levels of leptin (P<0.01), fasting insulin (P<0.01), and HOMA-IR (P<0.01), but lower IGFBP-3 (P=0.0001), fibrinogen (P=0.0001), and lipoprotein(a) (P<0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P=0.0016). CONCLUSIONS: Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.

Growth factors and adipocytokines in prepubertal children born small for gestational age: relation to insulin resistance.

OBJECTIVE: The aim of this study was to test whether being born small for gestational age (SGA) has an impact on adiponectin and leptin levels and the IGF system in relation to insulin sensitivity, taking into consideration the severity of growth restriction. RESEARCH DESIGN AND METHODS: Serum levels of adiponectin, leptin, fasting glucose, fasting insulin (I(F)), the homeostasis model assessment insulin resistance index (HOMA-IR), IGF-1, free IGF-1, IGF-binding protein (IGFBP)-1 and -3, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were evaluated in 57 children at age 4-10 years. Of these, 32 had been born appropriate size for gestational age (AGA) and 25 SGA (14 in the <3rd percentile and 11 in the 3rd-10th percentile). RESULTS; The SGA 3rd-10th percentile children were already insulin resistant at prepubertal age (I(F) 39.6 +/- 16.8 vs. 27 +/- 12 pmol/l, P < 0.01, and HOMA-IR 1.4 +/- 0.6 vs. 0.95 +/- 0.42 in SGA vs. AGA children, P < 0.05). Their IGF-1 and IGFBP-3 concentrations were significantly lower than those in AGA children (160.4 +/- 66.2 vs. 207 +/- 66.8 microg/l, P < 0.05 and 2.3 +/- 0.4 vs. 3.51 +/- 1.21 mg/l in SGA vs. AGA children, P < 0.01). The SGA <3rd percentile children had higher adiponectin (15.6 +/- 5.7 mg/l, P < 0.05) and IGFBP-1 levels (113.5 +/- 33.9 microg/l, P < 0.05) than AGA children (11.3 +/- 6.6 mg/l and 90.8 +/- 24.2 microg/l, respectively) and lower IGF-1 and IGFBP-3 concentrations (162.6 +/- 68.4 microg/l, P < 0.05 and 2.4 +/- 0.7 mg/l, P < 0.01). They also had significantly lower waist circumference (P < 0.05). Leptin levels did not differ among groups, but an inverse correlation with IGFBP-1 (r = -0.55, P < 0.01) was found in the pooled SGA group. CONCLUSIONS: Intrauterine growth restriction appears to affect the IGF axis at prepubertal age, and its severity plays a role in insulin sensitivity.

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.

Urinary lithogenic and inhibitory factors in preterm neonates receiving either total parenteral nutrition or milk formula.

UNLABELLED: The aim of this study was to evaluate prospectively the influence of nutrition on certain factors which may inhibit or promote nephrocalcinosis in two groups of preterm infants, receiving total parenteral nutrition (TPN) and special preterm milk formula respectively, but not furosemide. A total of 37 preterm infants, 15 on TPN and 22 fed a special preterm formula were studied at the end of the 1st, 2nd and 3rd weeks of life, at which time serum and 8 h urine specimens were collected. High ratios of urinary calcium to urinary creatinine (UCa/cr), urinary oxalate to urinary creatinine (Uox/cr) and urinary calcium to urinary citrate (UCa/cit) indicates an increased risk for nephrocalcinosis while high urinary citrate to urinary creatinine (Ucit/cr) ratio indicates protection. Uox/cr increased significantly (P<0.05) in those infants fed preterm formula, from the end of 2nd week of life and was two-fold higher than in the TPN group of preterm infants (P<0.01). Ucit/cr was higher throughout the study period in the formula fed than in the TPN preterm infants. UCa/cit was five-fold higher (P<0.01) in the TPN group, by the end of the 3rd week. Urinary calcium and magnesium was similar in both groups during the study period. Two of the infants studied (5.4%), one from each group, developed nephrocalcinosis. CONCLUSION: In preterm neonates on total parenteral nutrition, urinary oxalate -to-creatinine ratio (a potent lithogenic factor) was lower and urinary citrate -to-creatinine ratio (a lithoprotective factor) also lower than in formula fed neonates. The type of feeding (total parenteral nutrition or special preterm milk formula) seems to affect urinary oxalate and citrate but not calcium and magnesium in non-furosemide treated preterm infants during the first 3 weeks of life.