Intramyocellular lipid, adiposity, and muscle oxygen supply in prepubertal type 1 diabetes

Abstract:  Background: In the non-diabetic population, intramyocellular lipid (IMCL) accumulation is associated with obesity and poor muscle oxygen supply. IMCL levels are increased in type 1 diabetes, but their significance is less clear.
Methods:  We studied a group of 16 prepubertal boys (age 6.4–9.9 yr) with type 1 diabetes and a range of glycemic control [hemoglobin A1c (HbA1c) 6.4–10.2%]. Children's adiposity was assessed by anthropometry, muscle oxygen supply by near-infrared spectroscopy (NIRS), abdominal and IMCL content by magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS).
Results:  IMCL content did not associate with muscle reoxygenation rate, abdominal adiposity, duration of diabetes, or recent glycemic control. Muscle reoxygenation rate correlated with percentage body fatness (r² = 0.46, p = 0.004), visceral (r² = 0.45, p = 0.007) and abdominal subcutaneous fat volume (r² = 0.63, p = 0.0004), and dietary fat intake (r² = 0.27, p = 0.03) but not with the duration of diabetes nor HbA1c. HbA1c was significantly related to dietary fat intake only (r² = 0.28, p = 0.03).
Conclusion:  While causality cannot be inferred, interventions aimed at improving muscle oxygen supply, or preventing its deterioration, might reduce the development of adiposity in children with type 1 diabetes.     

REDUCED SERUM 1,25-(OH)2 VITAMIN D3 LEVELS IN PREDNISONE-TREATED ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract. The serum levels of 1,25-(OH)₂ vitamin D₃ were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D₃ may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D.     

VITAMIN D NUTRITIONAL STATUS OF PREMATURE INFANTS SUPPLEMENTED WITH 500 IU VITAMIN D2 PER DAY

ABSTRACT. The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D₂ per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D₃ fortified formula. Gestational age was 32.2±2.4 weeks (mean ± 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values ( r =0.81). The infants' mean plasma concentration increased from 30.6±13.7 nmol/l (mean±1 SD) after birth to 46.3±10.5 nmol/l after 9±1 days ( p <0.0025), and to 65.3±16.6 nmol/l after 37±10 days of vitamin D₂ treatment ( p <0.0005). 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined separately, and it appeared that the rise was accounted for by the D₂ fraction while 25-hydroxyvitamin D₃ concentrations were unchanged. The results demonstrate that vitamin D₂ is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.     

Nutritional rickets and z scores for height in the United Arab Emirates: To D or not to D?

Background: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D₂ (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency.
Methods: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment.
Results: The improvement in z score after treatment was 0.86 ± 0.95. The 95% confidence interval for the mean difference was 1.32–0.40 ( t  = 3.95, P  < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D₃ (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r  = 0.59, 95%CI: 0.15–0.84; P  = 0.01), indicating that younger infants had the lowest 25D levels.
Conclusion: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets.     

Premature Cranial Synostosis in X-Linked Hypophosphatemic Rickets: Possible Precipitation by 1-alpha-OH-Cholecalciferol Intoxication

ABSTRACT. A child suffering from X-linked hypophosphatemic rickets developed vitamin D intoxication under treatment with 1-alpha-OH-cholecalciferol (1(OH)D₃) and phosphorus. Beside the usual findings in this condition he showed precocious synostosis of the skull with signs of raised intracranial pressure. In view of earlier reports of coincidence of craniostenosis and X-linked hypophosphatemic rickets, we conclude that the possibility exists that intoxication with 1(OH)D₃ has been the precipitating factor. In addition we found hypersensitivity to 1 (OH)D₃ 2 months after cessation of treatment, and normal levels of calcitriol (1,2S(OH)₂D₃) at the same time.     

Insulin-related metabolism following hematopoietic stem cell transplantation in childhood

Objectives:  To assess insulin-related metabolism following hematopoietic stem cell transplantation (HSCT) in childhood.
Study design:  Thirty-four patients who underwent HSCT were compared with 21 patients with similar diseases who were not transplanted. Median follow-up was 3.6 yr after HSCT. Anthropometric parameters, fasting plasma glucose and insulin levels, hemoglobin A_1c (HbA_1c) and lipid profile were measured and compared.
Results:  HbA_1c was significantly higher (p = 0.001) in the study group. Two (5.8%) patients in the study group developed type 2 diabetes mellitus. Among thalassemic patients, significantly lower insulin resistance indices (p = 0.05) and fasting plasma insulin levels (p = 0.033) were found in the study group compared with the control group.
Conclusions:  Attentive follow-up of insulin-related metabolism following HSCT in children is needed. The significance of the higher HbA1c values in the study group remains to be evaluated in a larger cohort of patients.     

Vitamin D Metabolism in Pre-Operative Extrahepatic Biliary Atresia

ABSTRACT. In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)₂D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D₂ tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)₂D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D₂ tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25-hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia.     

THE PLASMA LEVELS OF 25-HYDROXYVITAMIN D IN PATIENTS WITH VARIOUS LIVER DISEASES AND THE RESPONSE OF 25-HYDROXYVITAMIN D TO VITAMIN D TREATMENT

ABSTRACT. The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D₂ for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5±3.7 (S.E.) ng/ml to 34.0±6.8 (S.E.) ng/ml after administration of vitamin D₂ in controls ( p <0.05). The mean plasma level of 25-OH-D also increased from 8.0±2.1 (S.E.) ng/ml to 22.1±2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group ( p <0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect the plasma levels of 25-OH-D.     

Effect of individualized weight-loss programmes on adiponectin, leptin and resistin levels in obese adolescent boys

Aim:  We investigate the effects of a 2-month weight-loss programme on plasma levels of adiponectin, leptin and resistin in obese adolescent boys.
Methods:  Twenty-one obese adolescent boys (BMI = 30.8 ± 3.2 kg/m²) completed the weight-loss programme including: 1/ either energy restriction (R), 2/ or individualized exercise training at the point of maximum lipid oxidation (Lipox_max) (E), 3/ or energy restriction and training (RE). Body composition, lipid oxidation and plasma levels of adiponectin, leptin and resistin were measured before and after intervention.
Results:  Following the weight-loss programme, adolescents of the RE group showed an improvement of their body composition (p < 0.01), an increase in plasma adiponectin (+73.7%, p < 0.01) and a decrease in plasma leptin (−38.8%, p < 0.01) leading to an increase in adiponectine/leptin ratio (ALR, +144.4%, p < 0.01) higher than the R or E groups. E and RE groups only showed a similar significant increase in plasma resistin (p < 0.05) and a significant improvement of lipid oxidation rate at Lipox_max (p < 0.01 and p < 0.001). In addition, in RE group, ALR is correlated with waist/hip and waist/height ratios, resistin level, homoeostasis mode assessment (HOMA-IR) index and Lipox_max.
Conclusion:  In obese adolescents boys, moderate exercise training completed at Lipox_max and combined with energy restriction improves their ability to oxidize lipids, which is associated with a normalization of their adiponectin, leptin and resistin levels resulting in an improved insulin sensitivity, as attested by a higher ALR and a lower HOMA-IR.     

Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: A pilot study

Cysteinyl leukotrienes (cys-LTs), LTB₄ and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB₄ and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756  m). Sputum eosinophil percentage and measurement of cys-LTs, LTB₄ and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 ± 1.1% at T0 and 3.5 ± 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 ± 0.5% at T0 and 1.5 ± 1.0% at T1 (ns). Cys-LTs mean level was 14.24 ± 4.53 pg/ml at T0 and 4.65 ± 0.68 pg/ml at T1 (p = 0.0125). LTB₄ level was 2.36 ± 0.19 pg/ml at T0 and 2.41 ± 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 ± 3.18 pg/ml at T0 to 7.36 ± 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.     

Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

Abstract:  To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days −3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm² (day -3) vs 1477 mm² (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm² (day -3) vs 648 mm² (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation, and peaked after the day of graft infusion (day 0). sTNFRI levels at day 0 predicted changes in weight SDS (r = 0.65; p = 0.05), triceps skinfold SDS (r = 0.85; p = 0.007) and gastrointestinal dysfunction (r = 0.88; p = 0.004). Likewise, IL-1Ra levels at day 0 correlated with the gastrointestinal dysfunction (r = 0.83; p = 0.01) and with the change in weight SDS (r = 0.77; p = 0.03). This study suggests that pretransplant levels of inflammatory markers are associated with posttransplant symptoms of gastrointestinal dysfunction and loss of both fat and lean body mass. Future studies should adress if the use of conditioning regimens with limited proinflammatory cytokine inducing activity, anti-inflammatory agents, or more optimised nutritional support can reduce the burden of such posttransplant complications.     

Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes

Objective:  To determine if use of an injection port, the Insuflon™, would help to improve glycemic control in youth with type 1 diabetes (TID) who were in suboptimal glycemic control (hemoglobin A1c, HbA1c >8.0%).
Study design:  A three-arm randomized protocol was used to study the effects of the Insuflon (a subcutaneous injection port) vs. an alarmable blood glucose meter vs. a control group on glycemic control in 66 youth with T1D. All participants used insulin glargine™ as their basal insulin and the NovoPen^® Junior with insulin aspart™ as their rapid-acting insulin. Participants were randomized into control, alarm, or Insuflon groups. HbA1c levels were the primary outcome with values at baseline, 3, and 6 months.
Results:  Initial parameters were similar in the three groups. HbA1c values were significantly lower for youth who used the Insuflon than for the control group at 3 and 6 months (p = 0.025). The HbA1c values (in %) for youth using the Insuflon decreased significantly from 9.4 at screening to 8.7 at 3 months (p < 0.001) and 8.5 at 6 months (p < 0.001). There were no significant reductions (p ≥ 0.05) in the HbA1c values within the other two groups.
Conclusion:  The Insuflon injection port helps some youth with T1D to improve glycemic control.     

Time series analysis of ultraviolet B radiation and type 1 diabetes in Newfoundland

Background:  Type 1 diabetes mellitus (T1DM) has been previously been associated with decreased levels of vitamin D. This study investigates the temporal association between average daily ultraviolet B (UVB) irradiance and T1DM in Newfoundland.
Methods:  A complete list of patients diagnosed with T1DM in the province of Newfoundland and Labrador was constructed using multiple sources. Pooled and unpooled monthly incidence data along with monthly UVB measurements were used to build a time series transfer function model. The model was used to predict the future incidence of T1DM based on previous monthly trends, and these predictions were compared with actual measured incidences.
Results:  A seasonal variation in pooled monthly incidence was observed. The transfer function model was able to reasonably predict the future incidence of T1DM based on previous observations and monthly UVB measurements. Tests of seasonality demonstrated a significant seasonal trend (p = 0.0003).
Conclusions:  This study suggests that erythemal UVB radiation may be temporally associated with the incidence of T1DM.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.     

25-羟维生素D与儿童1型糖尿病及酮症酸中毒的相关性研究

目的探讨血清25-羟维生素D[25-(OH)D]水平与儿童1型糖尿病(T1DM)及酮症酸中毒(DKA)的相关性。方法选取2006年1月—2009年12月期间152例住院患儿,其中52例为首次发病的T1DM患儿,包括酮症酸中毒(DKA组)21例,以及非酮症酸中毒(非DKA组)31例,其余100例为非T1DM组。检测并比较三组患儿的血清25-(OH)D水平,分析血清25-(OH)D水平与儿童T1DM及DKA的相关性。结果 DKA组患儿的血清25-(OH)D平均为(53.6±27.8)nmol/L,显著低于非DKA组的(69.7±27.9)nmol/L和非T1DM组的(81.8±28.3)nmol/L(P<0.05);非DKA组患儿的血清25-(OH)D水平显著低于非T1DM组(P<0.05)。结论 T1DM患儿的血清25-(OH)D水平低,尤以DKA患儿最为明显,维生素D在儿童T1DM发病中的潜在保护效应值得关注。     

Thyroid autoimmunity in children with features of both type 1 and type 2 diabetes

Aim/hypothesis:  To assess the prevalence of autoimmune thyroid disease (ATD) in insulin-treated youth with clinical features of type 2 diabetes mellitus (T2DM).
Methods:  We evaluated prevalence of thyroid peroxidase (TPO) and thyroglobulin (TGA) antibodies at onset of insulin-treated diabetes and follow-up in 183 White and Black children. Of these, 136 had a body mass index (BMI) <85th percentile with 122 (89%) positive for β-cell autoimmunity [type 1 diabetes mellitus (T1DM)/group I], 25 were overweight (BMI ≥85thpercentile) with or without acanthosis nigricans with β-cell autoimmunity ['double' diabetes (DD)/group II], and 22 were overweight with no conventional β-cell autoantibodies (group III).
Results:  The prevalence of TPO and/or TGA was 39 and 29% (p = 0.19) in White and Black children and 39, 32, and 0% (p = 0.007) in groups I, II, and III, respectively. After a median follow-up of 60 months, 3.7, 4.3, and 0% developed hypothyroidism (increased thyroid-stimulating hormone with or without decreased free T4) in groups I, II, and III, respectively (p = 0.6). In subjects with TPO and/or TGA, hypothyroidism developed in 10 and 14% of groups I and II, respectively (p = 0.7). No child without thyroid antibodies developed hypothyroidism.
Conclusions:  In patients with clinical features of T2DM who have evidence of β-cell autoimmunity (DD), the frequency of thyroid antibodies and ATD is similar to that in classical T1DM. This suggests that TIDM comorbidities may be common in clinical T2DM patients who have β-cell autoimmunity. Despite their obesity, youth with insulin-requiring diabetes should be screened for thyroid and possibly other T1DM-associated autoimmune diseases.     

Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus

Objective:  The purpose of this study was to determine the effect of adjuvant premeal pramlintide with postmeal insulin on postprandial hyperglycemia in children with type 1 diabetes mellitus (T1DM).
Methods:  Eight adolescents with T1DM on intensive insulin therapy participated in an open-label, non-randomized, crossover study, comparing postprandial glucose excursions in study A (prescribed insulin regimen and given premeal) vs. study B (pramlintide + insulin). Prandial insulin dose for study B was decreased by 20% and given postmeal, while pramlintide was given just before the meal. Blood glucose (BG), glucagon, and pramlintide concentrations were measured basally and at timed intervals during a 300-min study period.
Results:  Postprandial incremental BG for the duration of the study was reduced in study B vs. study A with AUC_{(−60 to 300 min)} (area under the curve) at 6600 ± 2371 vs. 20 230 ± 3126 mg/dL/min (367 ± 132 vs. 1124 ± 174 mmol/L/min) (p < 0.001). Glucagon concentration was suppressed for ∼120 min following administration of 30 μg of pramlintide and postmeal insulin (p < 0.003). No severe hypoglycemic episodes were experienced in this study.
Conclusions:  Postprandial hyperglycemia is considerably reduced in adolescents with T1DM when treated with fixed-dose premeal pramlintide, and precisely calculated postmeal insulin, without significant side effects.     

One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangements

Background:  Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.
Objective:  To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements.
Methods:  CF population was screened for glucose tolerance. CF patients with age >10 yr were screened with fasting hyperglycemia (FH). CF patients with age >10 yr without FH and those with age <10 yr with occasional FH were evaluated for glucose abnormalities on the basis of oral glucose tolerance test and/or continuous glucose monitoring system. All CF patients with glucose derangements were enrolled in an open clinical trial with glargine. Body mass index (BMI) z-score, forced expiratory volume in the first second (FEV₁), number of acute pulmonary exacerbations and hemoglobin A1c, were as outcome measures at baseline and after 1 yr of treatment.
Results:  After 12 months of therapy, BMI z-score improved only in patients with baseline BMI z-score less than −1 (p = 0.017). An 8.8% increase in FEV₁ (p = 0.01) and 42% decrease in the number of pulmonary exacerbations (p = 0.003) were found in the whole group compared with previous 12 months of therapy.
Conclusion:  Glargine could represent an innovative strategy to prevent lung disease progression in CF patients with early glucose derangements. Larger controlled trials are needed to better clarify the effects of insulin on clinical status in CF patients with early glucose derangements.     

The occurrence of primary nocturnal enuresis and associated factors in 5-year-old outpatients in Slovenia

Aim:  To determine the occurrence of primary nocturnal enuresis in 5-year-old outpatients in Slovenia and the possible correlations with different factors.
Methods:  The epidemiological study was conducted in Slovenia between 2005 and 2007. A special questionnaire was distributed randomly among the parents of 1846 5-year olds in children's outpatient clinics in all regions of Slovenia.
Results:  The response rate was on average 71.0%, which means that 7% of all Slovenian 5-year olds were included in the study. The occurrence of primary nocturnal enuresis was 8.7% and was higher in families with many siblings (χ² test, p < 0.01). The boy:girl ratio was 1.4 (Student t -test, p = 0.024). Parents were found to be more disturbed by the problem than their children (χ² test, p < 0.01). The maternal and paternal education levels of children with primary nocturnal enuresis did not differ from the Slovenian adult population (χ² test, p > 0,05).
Conclusion:  The occurrence of primary nocturnal enuresis in 5-year-old outpatients in Slovenia is comparable with data from other countries. Primary nocturnal enuresis is more frequent in boys than in girls, with higher occurrence in families with more siblings, and parents are more disturbed by the problem than their children.