Supplementation with Three Different Daily Doses of Vitamin D3 in Healthy Pre-pubertal School Girls: A Cluster Randomized Trial.

OBJECTIVE: To compare the adequacy and efficacy of different doses of vitamin D3 in pre-pubertal girls. DESIGN: Cluster Randomized controlled trial. SETTING: Public school in Delhi, India, between August 2015 and February 2016. PARTICIPANTS: 216 healthy pre-pubertal girls, aged 6.1-11.8 years. INTERVENTION: Daily supplementation with 600 IU (n=74), 1000 IU (n=67) or 2000 IU (n=75) of vitamin D3 under supervision for 6 months. OUTCOME MEASURES: Primary: Rise in serum 25 hydroxy Vitamin D (25(OH)D); Secondary: Change in bone formation and resorption markers. RESULTS: Following 6 months of supplementation, the mean (SD) rise in serum 25(OH)D was maximum with 2000 IU (24.09 (8.28) ng/mL), followed by with 1000 IU (17.96 (6.55) ng/mL) and 600 IU (15.48 (7.00) ng/mL). Serum 25(OH)D levels of ≥20 ng/mL were seen in 91% in 600 IU group , 97% in 1000 IU group and 100% in 2000 IU group. The overall mean (SD) rise in urinary calcium creatinine ratio (0.05 (0.28) to 0.13 (0.12) mg/mg), and serum procollagen type I N-terminal propeptide (538.9 (199.78) to 655.5 (218.24) ng/mL), and reduction in serum carboxy-terminal telopeptide (0.745 (0.23) to 0.382 (0.23) ng/mL) was significant (P<0.01). The change in the above parameters was comparable among the three groups after adjustment for age. CONCLUSIONS: Daily vitamin D supplementation with 600 IU to 2000 IU for 6 months results in Vitamin D sufficiency in >90% of pre-pubertal girls.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the North India cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from North India. RESULTS: A total of 4912 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 3619), insulin detemir (n = 880), insulin aspart (n = 331), basal insulin plus insulin aspart (n = 37) and other insulin combinations (n = 44). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.8%) and insulin user (mean HbA1c: 9.8%) groups. After 24 weeks of treatment, both the study groups showed improvement in HbA1c (insulin naïve: -2.7%, insulin users: -2.6%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Presentation and clinical course of Wolfram (DIDMOAD) syndrome from North India.

AIMS: Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. METHODS: Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. RESULTS: Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 ±7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in 4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. CONCLUSIONS: The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.

Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness--its relationship with severity and outcome of the disorder.

BACKGROUND: Non-thyroidal illness is a common cause of alterations in thyroid hormone economy in absence of underlying intrinsic thyroid disorder. OBJECTIVE: To study the prevalence and pattern of alterations in thyroid hormone economy in various non-thyroidal illnesses in our region and also to correlate these alterations with the severity and outcome of the non-thyroidal illness. MATERIAL AND METHODS: We analyzed circulating T3, T4, TSH in 382 patients with non-thyroidal illness (285 acute and 97 acute on chronic) and correlated the alterations with severity and outcome of the non-thyroidal disorder. The patients had one or more organ failure at the time of enrollment to the study. The hormones were estimated at the onset of sickness, and at 3rd and 24th week. T3, T4 and TSH in 75 age and sex matched euthyroid subjects were taken as controls. RESULTS: T3 (mean +/- SEM) was significantly reduced at the onset of illness, in both acute and chronic patient groups (1.61 +/- 0.05 nmol/l) compared to that in the controls (3.17 +/- 0.06 nmol/l). In spite of clinical improvement in most instances, T3 continued to remain low in the 3rd week (1.49 +/- 0.11 nmol/ l) but increased (2.14 +/- 0.09 nmol/l) in 24th week. Low T3 was found in 93 (32.6%) cases with acute illness in 20 (20.6%) cases with chronic illness. A combination of low T3 and T4 was found in 35 (12.3%) of cases with acute and 15 (15.5%) with chronic illness. Although serum TSH showed noticeable fall and rise in some individuals, no significant difference in mean TSH was observed during any period of illness compared to that in the controls. Severity of illness correlated with decrease in T3 (r=0.58) and T4 (r=0.38). A low T3 and T4 with low or undetectable TSH were associated with increased mortality. At the onset of acute illness low T3 was seen in 113 (29.6%, low T3 -low T4 in 50 (13.1%), high T4 in 28 (7.3%) lowT3-lowT4- low TSH in 10 (2.6%) and low T4 alone in 4 (1%) patients. Fifty one 1 (13.4%) of our patients demonstrated alterations in TSH in presence of normal T3 and T4-26 patients had decreased TSH while as 25 had increased TSH. Of 118 patients who followed at 24 weeks, 11 (9.3%) had low T3, 7(5.9%) had low T3- low T4 and 13 (11%) had elevated TSH. CONCLUSION: Pattern and prevalence of sick euthyroid syndrome in this part of the world, a recognized iodine deficient region, appears to be similar to that reported elsewhere. Important finding in our study was higher percentage of TSH elevation, which we believe to reflect the underlying iodine deficiency state of our community. Besides a significant number of subjects persisted with alterations in thyroid functions even after 6 months of therapy. Though the severity of thyroid hormone derangement correlated with severity of sickness, the derangement was similar in acute vs. acute on chronic nonthyroidal illnesses.

Puerperal alactogenesis with normal prolactin dynamics: is prolactin resistance the cause?

OBJECTIVE: To determine the cause of puerperal alactogenesis in a young woman. DESIGN: After proper clinical assessment, a definitive investigative protocol was followed to determine the cause of alactogenesis. SETTING: Tertiary care medical center in Kashmir, India. PATIENT(S): A young married woman with three full-term deliveries, all characterized by puerperal alactogenesis. INTERVENTION(S): An investigative protocol to document prolactin reserve and mammography to demonstrate presence of normal breast tissue. MAIN OUTCOME MEASURE(S): Prolactin secretory reserve. RESULT(S): The patient had normal breast development and an adequate pituitary prolactin reserve. CONCLUSION(S): Prolactin resistance may have caused alactogenesis.

Pseudovitamin D deficiency rickets--a report from the Indian subcontinent.

Pseudovitamin D deficiency rickets (also called vitamin D dependent rickets type I) is one of the types of inherited rickets and is caused by a deficit in renal 25-hydroxyvitamin D 1alpha-hydroxylase. This form of rickets has not been reported from the Indian subcontinent. Three patients with this disorder are presented. These patients were all females aged 3-20 years and presented with growth failure and skeletal deformities. All had florid clinical and radiological rickets. The biochemical abnormalities seen included hypocalcaemia, hypophosphataemia, and hyperphosphatasia. All patients had grossly raised 25-hydroxyvitamin D concentrations and markedly low to undetectable concentrations of 1,25-dihydroxyvitamin D. A disturbing feature of this study was the late referral of the patients.