Sudipta Misra

Lower Uncarboxylated Osteocalcin Concentrations in Children with Prediabetes Is Associated with β-Cell Function

CONTEXT Although animal studies suggest that it is the uncarboxylated rather than carboxylated form of osteocalcin that affects glucose homeostasis, the human data are scant and equivocal. OBJECTIVE This study investigated associations of uncarboxylated and carboxylated forms of osteocalcin with insulin sensitivity and β-cell function in 140 overweight prepubertal children (43% female, 46% black, 84% obese) with normal glucose levels (n = 99) and prediabetes (n = 41). METHODS An oral glucose tolerance test was used to identify prediabetes and for measurement of insulin sensitivity (Matsuda index), β-cell function [oral glucose tolerance test derived insulinogenic index and disposition index (DI(OGTT))] and uncarboxylated and carboxylated forms of osteocalcin. Visceral adipose tissue (VAT) was assessed using magnetic resonance imaging. RESULTS After controlling for age, sex and race, lower uncarboxylated osteocalcin concentrations, Matsuda index, insulinogenic index, and DI(OGTT) and higher VAT levels were found in the prediabetes vs. normal-glucose group (all P < 0.03). Carboxylated osteocalcin levels were not different between groups. Multiple linear regression adjusting for age, sex, race, and VAT revealed that uncarboxylated osteocalcin was associated with insulinogenic index and DI(OGTT) (β = 0.34, 0.36, respectively, both P < 0.04) in the prediabetes group but not the normal-glucose group. In both the normal-glucose and prediabetes groups, carboxylated osteocalcin was associated with insulin sensitivity (β = 0.26, 0.47, respectively, both P < 0.02). CONCLUSIONS These data suggest that the lower uncarboxylated osteocalcin concentrations found in children with prediabetes may be associated with β-cell dysfunction. In addition, our findings between carboxylated osteocalcin and insulin sensitivity suggest that carboxylated osteocalcin plays a role in human glucose homeostasis.

A Randomized Controlled Trial to Evaluate the Efficacy of Lactobacillus GG in Infantile Diarrhea

In a randomized, double-blind, placebo-controlled trial, 229 infants hospitalized for acute diarrhea in rural India were given a 10-day course of Lactobacillus rhammosus GG (minimum dose, 10 degrees bacteria) or placebo. There was no difference in groups in the duration of diarrhea or numbers of stool on days 3, 6, or 10 of treatment.

Chronic constipation in overweight children.

BACKGROUND Obesity and functional constipation seem to share a common biopsychosocial model of causation. Though chronic constipation can significantly affect the quality of life of an overweight child, this association has not been highlighted in the literature. The purpose of this study was to compare the proportion of overweight children among children with chronic constipation with a control group of children with normal bowel habits. METHODS Retrospective chart review with a control population. One hundred one consecutive children 5-18 years of age referred to the Subspecialty Clinic for functional constipation were the study group. The control group consisted of 100 consecutive children from the general pediatric practice seen for physicals and minor illnesses. Children with a body mass index (BMI) of >85 percentile from the National Institutes of Health (NIH) 2000 chart were classified as overweight. RESULTS The control and study groups were statistically comparable in mean age (10.97 +/- 3.83 years and 8.07 +/- 2.56 years, respectively) and gender ratio (58 males in each group). Thirty children in the control group and 44 in the study population were overweight (p < .05). Among children with chronic constipation, the group of overweight children was male predominant (70.45% vs 47.36%, p < .05), had increased incidence of psychological/behavioral problems (45.45% vs 22.8%, p < .05), and was more likely to fail treatment (40.9% vs 21.05%, p < .05). There was no significant difference in the clinical profile of constipation, such as mean duration of constipation before presentation, sex ratio, incidence of painful defecation, and soiling and frequency of defecation between these 2 groups. CONCLUSIONS There appears to be an association between chronic severe constipation and being overweight. Children with constipation are more likely to be overweight when compared with controls. Among children with chronic constipation, overweight individuals seem to constitute a distinct clinical group. This group is male predominant, has increased incidence of psychological/behavioral disorders, and is more likely to fail treatment.

Plasma Choline Concentrations in Children Requiring Long-Term Home Parenteral Nutrition: A Case Control Study

BACKGROUND Low plasma free choline concentration has been associated with elevated serum hepatic aminotransferase concentrations and hepatic steatosis in adults who need home parenteral nutrition (HPN). We sought to determine if plasma free choline is similarly reduced in children who need home total parenteral nutrition (TPN). METHODS We compared the plasma free choline concentration in 21 children who required long-term HPN with 31 normal controls. Patients had received HPN for 75 +/- 13 (SD) months (range 3-206 months). All control children ingested a normal, mixed, nonvegetarian diet. RESULTS The mean plasma free choline concentration in the children receiving HPN was significantly lower than normal children (6.6 +/- 4.3 vs 8.0 +/- 2.3 nmol/mL, p = .002). Plasma free choline concentration was correlated with age (r = -0.43, p = .049). Using multiple linear regression analysis for age, sex, and squared age (considered in order to account for possible nonlinearity between choline and age), HPN children showed a steady and significant decline in plasma free choline concentration with increased age at the rate of 0.03 nmol/mL per month. Plasma lipid bound choline concentration did not vary with age. No relationship was seen between either plasma free and lipid bound choline concentration and amount of daily IV lipid infusion. A significant negative correlation was observed between plasma free choline concentration and aspartate aminotransferase (AST) and alanine aminostransferase (ALT) (r = -0.72, p = .04 and r = -0.80, p = .02, respectively). CONCLUSION Our data support the notion that patients who need long-term HPN without significant enteral feeding have a significant risk for the development of choline deficiency with its associated hepatic dysfunction.

A Prospective Study of Rotavirus Diarrhea in Children Under 1 Year of Age

The aim of this study was to document the changing clinical profile and prognosis of acute diarrhea in infants. This was a prospective observational study with follow-up. Demographic, anthropometric, and clinical data were collected in children younger than 1 year with acute diarrhea. Stool was examined under the microscope, cultured, tested for presence of reducing substance and occult blood, and subjected to electrophoresis to detect rotavirus infection. Thirty-one (91.2%) of the 34 infants were breastfed, 18 exclusively and 13 partially. Twenty-three had rotavirus infection and had slower nutritional recovery than others. There was no difference in the incidence of rotavirus infection between exclusively and partially breastfed infants. Continuation of feeds containing lactose did not affect prognosis, though 23 (67.6%) infants had reducing substance in stool. We documented a high incidence of rotavirus infection, which negatively affected growth of infants by some ill-defined mechanism. Failure of exclusive breastfeeding to protect against rotavirus infection highlights the need for universal rotavirus vaccination. Lactose malabsorption detected in many infants did not affect prognosis after acute diarrhea.

Profile of anemia in children after liver transplantation.

Background. Clinical and hematological profile of chronic anemia in children after orthotopic liver transplantation (OLT) is unknown. Methods. We prospectively studied children after orthotopic liver transplantation (OLT) with hemoglobin levels < 2 standard deviation of age appropriate mean for > 6 months. Investigations included hemogram, reticulocyte count, peripheral blood smear, serum vitamin B-12, folic acid levels, iron studies, Coomb’s tests, serum erythropoietin (EPO) levels, and stool and urine tests for occult blood. Results. Fifty-six participants (22 male and 34 female, mean age 82.9 months, range 20–232, mean post-OLT duration 48.8 months, range 6–132) were studied. The causes of anemia were idiopathic (32), iron deficiency (4), viral infections (2, HIV=1, parvovirus=1), and lymphoproliferative disease (2). Fifteen participants showed spontaneous recovery within 1–6 months. Thirty-one children with idiopathic anemia had low or normal EPO levels (mean 7.33 m&mgr;/L, range <2.5 to 15.9, normal 4–24). When outliers (iron deficiency=4, HIV disease=1) were excluded, there was no statistical correlation between hematocrits and EPO levels. Serum vitamin B-12 levels (n=52) were elevated (normal 110–930 pg/ml) (mean=1186 pg/ml) in 32 (61.5%) and were significantly higher in those with abnormal liver function tests. Conclusion. Anemia is a common problem in children after OLT. More than half the participants had anemia of unknown etiology with an inappropriate EPO response for the degree of anemia. The normal negative correlation between hematocrit and EPO was lost in these children. The observation regarding serum vitamin B-12 levels requires further study.

Transpyloric feeding in gastroesophageal-reflux-associated apnea in premature infants.

Objective: The aetiological role of gastroesophageal reflux in apnea of prematurity is controversial. We hypothesized that transpyloric feeds, which decreases reflux and aspiration, will not be associated with decrease in reflux‐related apnea.

Is biliary scintigraphy a reliable diagnostic tool for biliary dyskinesia in children

Background and Aim The role of hepatobiliary scintiscan (HIDA) in children suspected to be having functional biliary tract disease has not been studied. We evaluated HIDA scan results as long-term prognostic indicators for biliary dyskinesia with or without intervention. Methods Children who had HIDA scan for chronic abdominal pain, nausea, or vomiting were included. These children had inconclusive gastrointestinal diagnostic workup. HIDA scan was performed according to a standardized protocol. Clinical data were collected by retrospective chart review. A telephonic survey was done 5 years after the initial HIDA scan to document long-term outcome. Results Forty-two of 61 children had abnormal HIDA scan. There was no difference between children with normal and abnormal HIDA results in clinical presentations, short-term (85.7% and 84.2%) and long-term (64.9% and 60%) outcomes. Twenty-seven of the 42 children with abnormal scan results underwent interventions (21 cholecystectomy only, 4 cholecystectomy followed by sphincter of Oddi sphincterotomy, and 2 sphincterotomy only). After intervention, children with abnormal HIDA scan had better short-term prognosis (88.9% and 54.5%), but their long-term prognosis (52.2% and 85.7%) was worse than those without intervention. No clinical prognostic factor could be identified. Conclusions HIDA scan result is not a good prognostic indicator in children with suspected biliary dyskinesia. Caution should be exercised while using HIDA scan for selecting patients for surgical intervention. Focused prospective studies are needed to define biliary dyskinesia in children.

Sphincter of Oddi dysfunction in children with recurrent abdominal pain: 5‐year follow‐up after endoscopic sphincterotomy

Background:   Sphincter of Oddi (SO) dysfunction has not been reported as a cause of recurrent abdominal pain (RAP) in children. We present a 5‐year follow‐up of a group of children with RAP and manometry proven SO dysfunction.

Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor–Deficient Mice

Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor-deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes.