Clinico-pathologic profile and outcomes of pediatric endocrine patients managed by endocrine surgeons: Experience over three decades in a tertiary center in India.

BACKGROUND: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. METHODS: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. RESULTS: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy. CONCLUSION: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.

Relative Adrenal Insufficiency in Decompensated Cirrhotic Children: Does It Affect Outcome?

INTRODUCTION: Relative adrenal insufficiency (RAI) is associated with poor outcome in adult cirrhotics. So far, pediatric studies are not available on the same. We aimed to prospectively study the presence and outcome of RAI in children with decompensated cirrhosis over 180 days. METHODS: Hemodynamically stable children with decompensated cirrhosis were sampled for serum basal cortisol and peak cortisol (after 30 minutes of 1-µg intravenous Synacthen) at day 1 and day 21. RAI was diagnosed as peak cortisol <500 nmol/L. Serum cytokines (interleukin-6 and tumor necrosis factor-α) and lipid profile were correlated with RAI. Cohort was followed up for outcomes over 180 days for complications and survival. With the identified risk factors, prognostic models were derived and compared with pediatric end-stage liver disease (PELD) and Child-Turcotte-Pugh scores. RESULTS: Prevalence of RAI was 54% at baseline and 61% at day 21 in the enrolled patients (n = 63, aged 128 ± 48 months, male 78%). No significant differences in cytokines and serum lipid levels were seen between RAI and normal adrenal function groups. Patients with RAI at baseline (D1-RAI) developed higher complications at follow-up as compared to the normal adrenal function group (53% vs 24%, P = 0.02). The PELD score (odds ratio 1.08, confidence interval 1.05-1.12, P < 0.01) and D1-RAI (odds ratio 3.19, confidence interval 1.32-7.73, P = 0.01) were independent predictors of follow-up complications. The PELD-delta cortisol model (area under the receiver operating curve 0.84, P < 0.001, 92% sensitivity; 60% specificity) predicted morbidity better than isolated PELD or Child-Turcotte-Pugh scores. DISCUSSION: RAI is a risk factor for development of complications in pediatric cirrhosis over short-term follow-up. The PELD-delta cortisol score is a promising prognostic model for predicting follow-up complications.

Prevalence and epidemiological profile of celiac disease in children with type 1 diabetes mellitus: Experience from a tertiary care center of India.

BACKGROUND: The HLA associations of celiac disease (CD) in north Indians differ from that in Europeans. Our dietary gluten is among the highest in the world. Data on CD in people with diabetes (PWD) in north India is scant. OBJECTIVE: To estimate the prevalence and clinical profile of CD in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Retrospective review of case records of PWD with onset ≤18 years of age, registered between 2009 and 2020, having at least one anti tissue-transglutaminase (anti-tTG) serology report. RESULTS: Of 583 registered PWD, 398 (68.2%) had celiac serology screening. A positive report was obtained in 66 (16.6%). Of 51 biopsied people, 22 (5.5%) were diagnosed to have CD, 12 in the first 2 years of diabetes onset. Symptomatic CD at diagnosis was seen in 63% (14/22). Age at diabetes onset (median [IQR] age 5.5 years, [2-12]) was lower in PWD and CD compared to PWD alone (10 years, [7-14], p < 0.016). Of 36 biopsied children with anti-tTG >100 au/ml, 20 (55.5%) had CD, while 2 out of 15 (13.3%) of those with lower anti-tTG titer had histopathology suggestive of CD. Of 23 seropositive children not diagnosed with CD, 5 of 8 with anti tTG >100 au/ml, and all 15 with lower anti-tTG, had normalization of titers over the 24 (10-41) months. CONCLUSIONS: Our prevalence of CD is comparable to international data. Celiac disease was common with younger age at onset of T1D and higher titer of celiac serology. A high proportion was symptomatic of CD at diagnosis.

High prevalence of idiopathic (islet antibody-negative) type 1 diabetes among Indian children and adolescents.

OBJECTIVES: To study the prevalence and clinical characteristics of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) among Indian children and adolescents at the time of diagnosis of illness. METHODS: In a hospital-based cross-sectional study, we studied 110 patients with T1DM aged ≤18 years. This included 61 patients with duration of diabetes ≤2 weeks (mean ± SD age of onset 9.9 ± 4.4 years) and 49 patients with duration 2 to 12 weeks. Antibodies against GAD65 (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A), detected by radio-binding assay, were measured in all patients. Insulin autoantibody (IAA) was measured only in subjects with duration ≤2 weeks, using a competitive radio-binding assay. RESULTS: The prevalence of GADA, IA-2A, and ZnT8A was 53%, 34%, and 29% respectively, while IAA (measured in 61 patients) was detected in 31%. All four antibodies were absent in 17 of 61 (28%) patients. The prevalence of islet antibody-negative patients was similar among both sexes and in children with onset younger and older than 10 years. ZnT8A was the only antibody detected in four patients, and its measurement resulted in 6% reduction in islet antibody-negative patients. Patients with idiopathic T1DM did not differ in their clinical features or fasting plasma C-peptide at the onset and after follow-up of 1 year. Compared with idiopathic T1DM, antibody-positive patients had an increased allele frequency of HLA DRB1*0301 (46% vs 14%, OR = 5.10 [confidence interval = 1.61-16.16], P = .003). CONCLUSION: Nearly 30% of Indian patients were negative for all islet antibodies at the onset of T1DM. Patients with idiopathic T1DM had similar clinical features to antibody-positive subjects.

Pediatric Primary Hyperparathyroidism: Experience in a Tertiary Care Referral Center in a Developing Country Over Three Decades.

BACKGROUND: There is limited experience in managing pediatric primary hyperparathyroidism (PHPT). The aim of this study was to analyze the clinical presentation and outcome of surgery in children with PHPT managed at a tertiary referral center. METHODS: This retrospective study (September 1989-August 2019) consisted of 35 pediatric PHPT patients (< 18 years) who underwent parathyroidectomy. Clinico-pathologic profile and outcome were noted. RESULTS: The mean age of cohort was 15.2±2.9 years and girls outnumbered boys (M:F = 1:1.9). Familial and symptomatic disease was noted in 8.5 and 94.3% cases, respectively. Skeletal manifestations (83%) were the commonest followed by renal (29%). Fifty-four percent children had skeletal fractures, and 23% were bed-ridden. Among rare manifestations, hypercalcemic crisis, recurrent pancreatitis and stigmata of rickets were observed in 2.8, 11.4 and 14.2% children, respectively. Mean calcium concentration was 12.1 ± 2.0 mg/dl and PTH 91.8 ± 66.5 pmol/L. The sensitivity of preoperative imaging in parathyroid localization was 91.4%. Minimally invasive parathyroidectomy (MIP) was performed in 40% cases. Parathyroid adenoma was observed in 91.4% patients, whereas remaining had hyperplasia. Thirty-four percent suffered from Hungry bone syndrome in postoperative period. The cure rate following primary surgery was 97%. One child with persistent PHPT had successful re-operation. Median follow-up was 5 (1-17) years, and no recurrence or familial disease was revealed during this period. CONCLUSION: Majority of pediatric patients present with symptomatic PHPT. Despite relatively high incidence of familial disease select pediatric patients can undergo successful MIP.

Vitamin D status of children in Kerala, southern India.

OBJECTIVE: To study plasma 25-hydroxyvitamin D (25(OH)D) status of children in Kerala, southern India, and its relationship with sociodemographic variables. DESIGN: Cross-sectional observational study. SETTING: Tertiary government hospital. PARTICIPANTS: Children (n 296) with trivial acute illness were enrolled. Sun exposure and Ca and vitamin D intakes (7 d dietary recall) were documented. Serum Ca, P, alkaline phosphatase, plasma 25(OH)D and parathyroid hormone (PTH) were measured. RESULTS: Prevalence of vitamin D deficiency (plasma 25(OH)D <30 nmol/l) was 11·1% (median, interquartile range (IQR): 52·6, 38·4-65·6 nmol/l). Children who ate fish daily had significantly higher plasma 25(OH)D than those who did not (median, IQR: 52·5, 40·8-68·9 v. 49·1, 36·2-60·7 nmol/l; P = 0·02). Those investigated in the months of March-May showed highest 25(OH)D v. those enrolled during other times (median, IQR: 58·7, 45·6-81·4 v. 45·5, 35·6-57·4 nmol/l; P <0·001). Plasma 25(OH)D correlated positively with serum P (r = 0·24, P <0·001) and Ca intake (r = 0·16, P 0·03), negatively with age (r = -0·13, P 0·03) and PTH (r = -0·22, P <0·001.). On linear regression, summer season (March-May), lower age, daily fish intake and higher Ca intake were independently associated with plasma 25(OH)D. CONCLUSIONS: Prevalence of vitamin D deficiency is low in Kerala. The natural fish diet of coastal Kerala and the latitude may be protective. Public health policy in India should take account of this geographical diversity.

The impact of free medical supplies and regular telephonic contact on glycemic control in Indian children and adolescents with type 1 diabetes.

BACKGROUND/OBJECTIVE: The effect of economic assistance to underprivileged families with type 1 diabetes has never been described. Such a study is relevant as logistic and cultural factors may preclude an anticipated good outcome. The objective of the study is to determine the impact of economic and educational intervention on hemoglobin A1c (HbA1c) and diabetes knowledge. METHODS: Eighty-five consecutive participants were prospectively provided insulin and glucose strips for 1 year. From the 6th to 12th month, patients were randomized such that half of them (telephone group) received proactive telephonic advice by a diabetes educator, while the non-telephone group received usual care. HbA1c and diabetes knowledge were measured at baseline, 6 and 12 months. RESULTS: Significant improvement was seen in HbA1c with provision of free diabetes supplies, when patients were compared with their own HbA1c values during the prior 36 months (baseline [8.38 ± 2.0%], at 3 months [8.0 ± 1.6%] and at 6 months [8.1 ± 1.5%, P = 0.0106]). Knowledge score increased from baseline (48 ± 15) to 6 months (58 ± 13, P < 0.001). No difference was seen between the telephone and non-telephone groups in HbA1c from the 6th to 9th and 12th month. The knowledge score showed significant improvement in the telephone group during the proactive telephonic advice study compared with the non-telephone group (P = 0.002). CONCLUSIONS: The provision of free medical supplies improved HbA1c and diabetes knowledge. Intensive telephone contact improved knowledge, not HbA1c. These results provide important background for policy makers and diabetes management teams.

Maternal vitamin D supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial.

We studied bone mineral content (BMC), bone mineral density (BMD), and body composition in offspring of women supplemented with vitamin D during pregnancy. Pregnant women were randomized to receive oral cholecalciferol 60,000 units 4 weekly (group 1), 8 weekly (group 2), or placebo (group 3). All received 1 g calcium daily (groups 1 and 2 without, and group 3 with 400 units vitamin D). Offspring at 12-16 months underwent dual-energy X-ray absorptiometry. Maternal hypovitaminosis D at recruitment was common (serum 25OHD <50 nmol/L in 88 %) and severe (25OHD <25 nmol/L in 46 %). Groups 1 and 2 (n = 23 and 13, median age 14 months) had higher cord blood 25OHD (47.8 ± 13.8 and 31.0 ± 14.0 nmol/L) versus group 3 (n = 16, median age 16 months, 17.8 ± 13.5 nmol/L, p < 0.001). Babies in group 3 had higher whole-body BMC (250.8 ± 42.5 gm) and BMD (0.335 ± 0.033 gm/cm2) compared to group 1 (213.1 ± 46.2 gm and 0.295 ± 0.041 gm/cm2) and group 2 (202.9 ± 29.9 gm and 0.287 ± 0.023 gm/cm2) (p = 0.006 and 0.001, respectively). In multivariate analysis, age, weight z score, and lean body mass remained significant contributors to BMC. Parameters of body composition were comparable among the groups. Vitamin D supplementation to pregnant women with severe deficiency in doses that improved cord blood 25OHD did not result in improved bone health or body composition in offspring at 12-16 months, compared to a dose too small to improve 25OHD levels.

Sun exposure, UV irradiance and serum 25-hydroxycholecalciferol in pregnant women in rural north India.

OBJECTIVE: To document the effect of season and environmental pollution on UVB irradiance; and to estimate cutaneous vitamin D synthesis in village women in different seasons. DESIGN: Radiant UVB energy was measured by a spectroradiometer in different seasons and, in April and May, on successive days in open areas at the city outskirts, at a crowded inner-city area and the villages of our participants. Clothing, outdoor activity pattern and serum 25-hydroxycholecalciferol (25(OH)D) levels were documented. SETTING: Rural north India, latitude 26·8°N. SUBJECTS: Pregnant women (n 139, aged 20-40 years). RESULTS: UVB irradiance ranged from 56 µW/cm2 in January to 470 µW/cm2 in June. Proportion of skin exposed was 18·5 % in summer and 9·5 % in winter. Mean (sd) daily duration of sun exposure was 3·2 (0·2) h during winter and 2·1 (0·4) h during summer. Cutaneous vitamin D synthesis was estimated to be 19·25 µg (770 IU) during winter and 37·25 µg (1490 IU) during summer. Mean (sd) serum 25(OH)D was 28 (15) nmol/l during winter (92 % of participants with 50 nmol/l). Mean (sd) UVB irradiance at peak summer was significantly higher at the open areas and in the villages than at the inner-city location (340 (45) and 310 (60) v. 250 (50) µW/cm2, P=0·03). CONCLUSIONS: In our population, at latitude 26·8°N, poor skin exposure is a limiting factor in all seasons. During winter, low UVB radiation energy also contributes. Particulate pollution limits UVB irradiance. Vitamin D supplementation during winter may be necessary.

Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial.

We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26°N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000µg/month oral vitamin D3 by the mother (group A) or 10µg/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45·3; interquartile range (IQR) 22-59·5 nmol/l) than in groups A (median 60·8; IQR 41·3-80·5 nmol/l (P7.5µkat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46·5; IQR 14·8-73·3 d) than in group A (median 18·5; IQR 8·8-31·0 d (P<0·01)) or group B (median 13·0; IQR 7·0-28·5 (P<0·05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3·5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity.

High direct costs of medical care in patients with Type 1 diabetes attending a referral clinic in a government-funded hospital in Northern India.

BACKGROUND: There is little information regarding costs of managing type 1 diabetes mellitus (T1DM) from low- and middle-income countries. We estimated direct costs of T1DM in patients attending a referral diabetes clinic in a governmentfunded hospital in northern India. METHODS: We prospectively enrolled 88 consecutive T1DM patients (mean [SD] age 15.3 [8] years) with age at onset <18 years presenting to the endocrine clinic of our institution. Data on direct costs were collected for a 12 months-6 months retrospectively followed by 6 months prospectively. RESULTS: Patients belonged predominantly (77%) to the middle socioeconomic strata (SES); 81% had no access to government subsidy or health insurance. The mean direct cost per patient-year of T1DM was `27 915 (inter-quartile range [IQR] `19 852-32 856), which was 18.6% (7.1%-30.1%) of the total family income. A greater proportion of income was spent by families of lower compared to middle SES (32.6% v. 6.6%, p<0.001). The mean out-of-pocket payment for diabetes care ranged from 2% to 100% (mean 87%) of the total costs. The largest expenditure was on home blood glucose monitoring (40%) and insulin (39.5%). On multivariate analysis, total direct cost was associated with annual family income (ß=0.223, p=0.033), frequency of home blood glucose monitoring (ß=0.249, p=0.016) and use of analogue insulin (ß=0.225, p=0.016). CONCLUSIONS: Direct costs of T1DM were high; in proportion to their income the costs were greater in the lower SES. The largest expenditure was on home blood glucose monitoring and insulin. Support for insulin and glucose testing strips for T1DM care is urgently required.

Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease.

BACKGROUND & AIMS: There are currently no published data on post-paracentesis circulatory dysfunction (PPCD) or its prevention in children. Our study was aimed to analyze the safety and complications of large volume paracentesis (LVP) in children with severe ascites due to chronic liver disease with or without albumin therapy. METHODS: A prospective longitudinal observational study enrolled children with severe ascites who underwent single time LVP at admission. They were divided into albumin infused (AI) and albumin non-infused (ANI) groups. Hemodynamic monitoring and laboratory parameters including plasma renin activity (PRA) were compared between baseline, 48 h and day 6 of LVP. Their outcome at 3 months and maximal follow-up were noted. RESULTS: 32 children (AI, n=17; ANI, n=15) had comparable baseline characteristics and 90.6% had high PRA at onset. The incidence of PPCD was 37.5% (ANI: 67%; AI: 12%, p=0.003), occurred if ascitic fluid extraction was >197.5 ml/kg (sensitivity: 90%; specificity: 50%, p=0.01) and if flow rate was higher in ANI group (1224 ± 476 vs. 678 ± 214 ml/h, p=0.009). ANI patients were susceptible to asymptomatic, persistent hyponatremia (baseline vs. day 6, 131 ± 4 vs. 128 ± 6 mEq/L; p=0.04) and had higher rates of recurrent ascites (42%) and hospital readmission (67%) within 3 months. No survival benefit among the AI or non-PPCD groups was demonstrated. CONCLUSIONS: LVP is safe in all age groups, best performed under albumin cover to overcome the problems of PPCD and hyponatremia. It is prudent to restrict volume extraction to less than 200 ml/kg actual dry weight for all and flow rate of 680 ml/h in ANI.

Growth and obesity status of children from the middle socioeconomic group in Lucknow, northern India: A comparison with studies on children from the upper socioeconomic group.

BACKGROUND: Children from the upper socioeconomic group in India currently show a modest positive secular trend in height, accompanied by a high prevalence of obesity. We examined the anthropometric pattern among children from the middle socioeconomic group. METHODS: A cross-sectional study of anthropometry in 3794 schoolchildren from the middle socioeconomic group in the city of Lucknow, Uttar Pradesh, India. RESULTS: A comparison with the data of a 20-year-old study of children from the upper socioeconomic group showed that the height of boys in our study was at par with or higher than that of boys of the same (Lucknow-Allahabad-Varanasi) region or national data, at all centiles. In contrast, girls in our study were shorter than national data at all centiles and shorter than girls of the same region at the 3rd centile. Children from the middle socioeconomic group did not show the large increase in weight centiles seen in the recent data of the upper socioeconomic group. The values of body mass index at the 85th and 95th percentile at 17 or 18 years of age in girls and boys were 23 and 25 kg/m2, respectively. Obesity was prevalent in 1% of children of the middle socioeconomic group and an additional 5.7% were overweight. CONCLUSIONS: Children from the middle socioeconomic group in Lucknow have grown taller than their 20-year-old counterparts from the upper socioeconomic group. Boys have fared better than girls. Children from the middle socioeconomic group in Lucknow are at present spared from the epidemic of obesity.

School-time Hyperglycemia and Prolonged Night-Time Hypoglycemia on Continuous Glucose Monitoring in Children With Type 1 Diabetes.

OBJECTIVE: To document glycemic patterns during school and sleep by continuous glucose monitoring system (CGMS) in school-going children with type 1 diabetes. To correlate glycemia with meal composition. METHODS: Patients with type 1 diabetes (n = 22) aged 4 to 19 years were enrolled. Food recording was taught, and a retrospective CGMS sensor was worn by them for 6 to 14 days. Dietary composition and glycemic patterns during school and sleep were analyzed. RESULTS: The mean (SD) of dietary carbohydrate was 62.9 (9.2)% of daily calories (high) and protein 13 (2.5) % (low). Sensor glucose > 180 mg/dL (hyperglycemia) was detected on 73% of 139 school day CGMS records and involved 58 % of the school time. Sensor glucose < 70 mg/dL (hypoglycemia) was present on 45% of 172 nights. Time below range was 20 (25) %. Mean (SD) protein content (g) of dinner was significantly higher when it included lentil (dal) than without [20.4 (9.7) vs 15.3 (8.3); P < 0.001]. Hypoglycemia occurred less often on nights with vs without dal for dinner (42.1% vs 51.7%; P = 0.048). CONCLUSIONS: Hyperglycemia during school hours was notable. The inclusion of lentil (dal) in the night meal in the traditional diet may reduce nocturnal hypoglycemia.

Beyond HbA1c: Identifying Gaps in Glycemic Control Among Children and Young People with Type 1 Diabetes Using Continuous Glucose Monitoring.

OBJECTIVES: To describe continuous glucose monitoring (CGM) derived glycemic variables, and study their association with HbA1c and socio-economic factors in young people with Type 1 diabetes mellitus (T1DM). METHODS: Ninety-two participants [age 15.7 ± 5.0 y (mean ± SD), HbA1c 8.0 ± 1.5% (mean ± SD)] wore a professional CGM sensor for 14 d. RESULTS: Median (IQR) time in range (TIR) was 41 (18)%. Participants spent 41 ± 20% of their day in hyperglycemia (>180 mg/dl), and 14 (13)% in hypoglycemia (<70 mg/dl). High glycemic variability (percent CV >36%) was seen in 92% participants. Older age at diagnosis was associated with higher TIR (ß = 0.267, p = 0.01), lower time above range (TAR) (ß = -0.352, p <0.001), but higher time below range (TBR) (ß = 0.274, p = 0.006). The use of NPH vs. glargine basal insulin was associated with higher TBR (ß = -0.262, p = 0.009) but lower TAR (ß = 0.202, p = 0.041). HbA1c showed negative correlation with TIR (r = -0.449, p <0.001) and TBR (r = -0.466, p <0.001) and positive correlation with TAR (r = 0.580, p <0.001) and mean glucose (r = 0.589, p <0.001). CONCLUSIONS: These data demonstrate wide gaps between the recommended vs. real world glycemic variables in patients with T1DM in this region on multiple daily insulin injections. CGM identifies glycemic variability and complements HbA1c in improving glycemic control.

Basic carbohydrate counting and glycemia in young people with type 1 diabetes in India: A randomized controlled trial.

OBJECTIVES: The aim of this study was to evaluate the effect on glycemic control and acceptability of basic carbohydrate counting (BCC) in children and young adults with type 1 diabetes (T1DM). METHODS: Ninety-two children and young adults (6-25 y of age) with T1DM were randomized to receive either routine nutrition education (RNE), which addressed food groups, glycemic index, and effects of food and exercise on glycemia, or learn BCC with personalized portion size education. A continuous glucose monitoring study and glycosylated hemoglobin (HbA1c) were performed at baseline and after 12 wk. The primary outcome was a change in time-in-range from baseline through 12 wk. A questionnaire on the acceptability of BCC was administered. RESULTS: At 12 wk, there was no significant difference in change in time-in-range between the two groups (BCC group: 1.2 ± 12.2; RNE group: 1.9 ± 12.3; P = 0.786). No significant changes were observed in the percentage of time that blood glucose was >180 or >250 mg/dL; <70 or <54 mg/dL; glycemic variability, percentage of nights with hypoglycemia and HbA1c. In subgroup analysis, there was a significant decrease in HbA1c in the BCC group among participants with higher maternal education (-0.5 versus 0.2, P = 0.042). The total score on the acceptability questionnaire was higher in the BCC group (P = 0.022). CONCLUSION: Among children and young adults in our region with T1DM, BCC provided flexibility in food choices and perception of greater ease of insulin adjustment. Although BCC was equivalent to RNE in terms of glycemic control, larger studies may reveal benefit in outcomes in certain subgroups.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant.

Hypovitaminosis D is common in India. In the present prospective partially randomised study of vitamin D (D3) supplementation during pregnancy, subjects were randomised in the second trimester to receive either one oral dose of 1500 µg vitamin D3 (group 1, n 48) or two doses of 3000 µg vitamin D3 each in the second and third trimesters (group 2, n 49). Maternal 25-hydroxyvitamin D (25(OH)D) at term, cord blood (CB) alkaline phosphatase (ALP), neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs (usual care). Median maternal 25(OH)D at term was higher in group 2 (58·7, interquartile range (IQR) 38·4-89·4 nmol/l) v. group 1 (26·2, IQR 17·7-57·7 nmol/l) and usual-care group (39·2, IQR 21·2-73·4 nmol/l) (P = 0·000). CB ALP was increased (>8.02 µkat/l or >480 IU/l) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 (P = 0·03). Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups. Birth weight, length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 (3·08 and 3·03 kg, 50·3 and 50·1 cm, 34·5 and 34·4 cm, 2·6 and 2·5 cm, respectively) v. usual care (2·77 kg, 49·4, 33·6, 3·3 cm; P = 0·000 for length, head circumference and fontanelle and P = 0·003 for weight). These differences were still evident at 9 months. We conclude that both 1500 µg and two doses of 3000 µg vitamin D3 had a beneficial effect on infant anthropometry, the larger dose also improving CB ALP and maternal 25(OH)D.

Vitamin D Status of School-Age Children in North India.

Information on vitamin D deficiency in prepubertal children is scarce. The authors studied calcium intake, sunlight exposure, serum calcium, alkaline phosphatase, 25-hydroxyvitamin (25OHD), and intact parathormone (iPTH) in the children (N = 135) attending the pediatric endocrinology clinic (declared normal after evaluation) and their healthy siblings. Serum 25OHD < 12 ng/mL was frequent (55.6%) and median (IQR) 25OHD lower [10.1 (11.4) ng/mL] in pubertal (n = 36) versus prepubertal (n = 99) children [36.4% (p < 0.05), 15.5 (13.2) ng/mL (p < 0.001)]. Girls had lower 25OHD [12.33 (10.32)] vs. [15.83 (13.37) ng/mL, p < 0.05], calcium intake [517.20 (405.5) vs. 623.6 (430.5) mg, p < 0.05], and minutes of sunlight exposure [MSE, 38.55 (42.86) vs. 63.4 (66.8) min, p < 0.01] than boys. MSE and body surface area (BSA) exposed were significant associations of 25OHD in a multivariate model. Vitamin D deficiency in children, both pubertal and prepubertal, assumes public health importance in the authors' region. Girls are at higher risk. Duration of sunlight exposure and BSA are modifiable factors.