Estimating Vitamin D threshold for the Indian population: Delving into the actual disease burden.

Background: Based on the current guidelines in practice, a vast majority of the healthy Indian population is vitamin D deficient. Since the serum 25 hydroxycholecalciferol (25HCC) levels are affected by race and skin pigmentation, the normal range of vitamin D may differ in the Indians compared to the Western population. This study attempted to determine a population-specific threshold for 25 HCC levels associated with adequate bone health and calcium and phosphate homeostasis in healthy Indians. Methods: Subjects aged 20-50 years were included in the study. The exclusion criteria were obesity, chronic renal disease, liver failure, diabetes mellitus, thyroid disorders, a recent history of fracture, constant joint pain, and postmenopausal status. In addition, participants on prescribed medication such as glucocorticoids, anticonvulsants, or antifungals, as well as vitamin D and calcium supplementation, were also excluded.Blood samples were analyzed for serum calcium, phosphate, alkaline phosphatase, 25HCC, 1,25dihydroxycholecalciferol, parathyroid hormone (PTH), procollagen type-I N propeptide, and C-terminal telopeptide of type 1 collagen.Locally estimated smoothing scatter plot (LOESS) curves and Spearman correlation were utilized to study the correlation of all the biochemical parameters with 25 HCC to achieve thresholds. Results: The study consisted of 270 healthy participants, out of which 97.8% were found to have vitamin D levels below 30 ng/ml. In addition, 8.8% had raised PTH, and 1.85% had hypocalcemia. Furthermore, 1.48% had raised serum alkaline phosphatase and hypophosphatemia, respectively. A weak inverse correlation was seen between 25 HCC and PTH (rs = -0.437, p < 0.001), as well as alkaline phosphatase (rs = -0.1475, p = 0.015), while a weak positive correlation was seen with serum phosphate (rs = 0.128, p = 0.047). Conclusion: For a healthy Indian population, the reference range of 25 HCC is much lower, and the lower limit of normal is approximately 13.5 ng/ml. This study indicates that vitamin D insufficiency in this population starts at 25 HCC values of 13.5 ng/ml and deficiency at 7 ng/ml.

Observational Study on Outcomes after Radioiodine Ablation in Hyperthyroid Patients.

Introduction: Radio-active Iodine (RAI) is a safe, definitive, and cost-effective modality of treatment that is used as the first line of treatment for Graves' hyperthyroidism by most endocrinologists. Very few reports are available from India, observational follow-up data is needed to determine the meaningful prognostic outcomes of RAI ablation in the Indian population. Aims: To study the outcomes in hyperthyroid patients undergoing RAI ablation. Materials and Methods: This observational cohort study was conducted at Department of Endocrinology at Indraprastha Apollo Hospital, New Delhi. A total of 82 hyperthyroid patients who underwent RAI ablation between June 2014 to June 2018 were enrolled. RAI dose was calculated arbitrarily in most cases; often by an empirical fixed dose based on the goiter size and RAIU. The patients were reviewed at 1, 3 and 6 months post-RAI ablation. During follow-up, along with a detailed clinical examination, free T4, free T3 and TSH were checked. Results: The dose of I-131 varied from 6 mCi to 14 mCi. Most of the patients were given RAI in the dose of 7.1-10 mci. About 63.4% of patients achieved hypothyroidism in 6 months, 6.1% in 1 month, 37.8% in 3 months, and 19.5% in 6 months. Gender, age, etiology of hyperthyroidism, baseline thyroid function, goiter, and ophthalmopathy did not affect outcomes after RAI ablation. Those who were not treated with antithyroid drugs prior to RAI therapy were found to have higher rates of conversion to a hypothyroid state. Conclusion: RAI can be given safely as the first line of treatment in Graves' disease and antithyroid drug naïve patients respond better to therapy.

Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis.

AIMS: No meta-analysis is available which has holistically analyzed efficacy and safety of once weekly thyroxine (OWT) vs. standard daily therapy (SDT) with regards to managing primary hypothyroidism. We undertook this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for clinical trials involving hypothyroid patients receiving OWT in intervention arm, and SDT in control arm. Primary outcome was to evaluate changes in serum thyroid stimulating hormone. Secondary outcomes were to evaluate alterations in total tetra-iodothyronine (TT4), total tri-iodothyronine (TT3), free T4 (FT4), free T3 (FT4), heart rate (HR), cardiac function, symptomatology, and adverse events. RESULTS: From initially screened 159 studies, data from four trials involving 294 patients were analyzed. Patients of OWT had significantly higher thyroid stimulating hormone (TSH) [mean difference (MD) +1.85 mU/L (95% confidence interval, CI: 0.95-2.75); P < 0.01; I 2 = 63%], comparable TT4 [MD -0.87 mcg/dl (95% CI: -2.98-1.24); P = 0.42; I 2 = 65%], and significantly lower TT3 [MD -15.7 ng/dl (95% CI: -29.9-1.51); P = 0.03; I 2 = 90%], following 6-weeks therapy. TT4 [MD 3.05 mcg/dl (95% CI: 1.44-4.66); P < 0.01], and FT4 [MD 0.56 ng/dl (95% CI: 0.04-1.08); P = 0.03; I 2 = 66%] were significantly higher 2 h after thyroxine intake, in people on OWT compared to SDT. TT4 levels were significantly higher 4 h after thyroxine intake in OWT as compared to SDT [MD 0.70 ng/dl (95% CI: 0.52-0.88); P < 0.01]. Following 4-8 h of intake of thyroxine, isovolumetric contraction time [MD 3.62 ms (95% CI: 1.93-5.31); P < 0.01; I 2 = 0%] and aortic ejection time/pre-ejection period ratio [MD 0.01 (95% CI: 0.00-0.02); P = 0.02; I 2 = 0%], were significantly higher in people on OWT as compared to SDT. CONCLUSION: OWT is associated with less efficient control of hypothyroidism at 6 weeks and may be associated with supraphysiologic elevation of thyroid hormone levels along with transient echocardiographic changes in some patients following 2-4 h of thyroxine intake.

Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledge METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events. RESULTS: Data from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12-24 weeks use, Hba1c [mean difference (MD) -0.13% (95% CI: 0.35 - 0.09%); P = 0.24; I2 = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 - 7.88 mg/dl); P = 0.09; I2 = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79-13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to -2.51 kg); P < 0.001; I2 = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62-2.64); P = 0.58; I2 = 59%] were comparable among groups. CONCLUSION: Remogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin.

Prevalence of glucose intolerance at 6 weeks postpartum in Indian women with gestational diabetes mellitus.

AIMS: Women with a history of gestational diabetes mellitus (GDM) have an increased risk for future glucose intolerance, and should be followed up with subsequent screening for the development of diabetes or pre-diabetes at 6-12 weeks postpartum. We studied the prevalence of glucose intolerance at 6 weeks postpartum in Indian women with GDM diagnosed according to ADA criteria. MATERIALS AND METHODS: This longitudinal study, conducted at a tertiary care centre, included 75 Asian-Indian women aged ≥18 years, with a diagnosis of GDM (as per ADA criteria), who were referred to the Endocrine Department at Indraprastha Apollo Hospital, Delhi. A 2-h 75 g oral glucose tolerance test (OGTT) was performed at 6 weeks postpartum. RESULTS: Out of the 75 women who had GDM and were recommended an OGTT at 6 weeks postpartum, 17.3% did not return for the test. Out of 62 women, one-third (33.8%) developed an abnormal OGTT at 6 weeks postpartum, while 66.1% had reverted to normal glucose tolerance. Impaired fasting glucose (IFG) was seen in 14.5%, 4.8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 6.4% had overt type 2 diabetes. CONCLUSION: Our study emphasizes the need for compulsory follow up OGTT for women with GDM in our part of the world in view of ethnicity and prevailing socio-cultural factors.

Novel mutation c.597_598dup in exon 5 of ABCC8 gene causing congenital hyperinsulinism.

Congenital hyperinsulinism (CHI), a clinically and genetically heterogeneous disease, characterized by the unregulated secretion of insulin from pancreatic ß-cells, is the most common cause of persistent hypoglycemia in infancy. Early diagnosis and maintenance of normoglycaemia are essential to prevent adverse neurodevelopmental outcomes. The most common and severe forms of CHI are caused by inactivating mutations in ABCC8 and KCNJ11 genes, encoding the two subunits of the pancreatic ß-cell ATP sensitive potassium channel (KATP). We report a case of neonatal CHI due to a novel homozygous recessive mutation in the ABCC8 gene.

Continuous glucose monitoring system for congenital hyperinsulinemia.

Blood glucose monitoring is a way of testing the concentration of glucose in the blood. The most recent advance is the development of continuous glucose monitoring system (CGMS) which gives 24 hour trend of blood sugar levels thus helping both the patient and the physician in achieving better glycemic control. CGMS in pediatric population is generally used for those on insulin pumps and those who are having fluctuating blood glucose levels. This case highlights the use of CGMS for a child with congenital hyperinsulinemia. It helped in close monitoring of blood glucose levels thereby identifying recurrent hypoglycemia, leading to a better control of blood glucose levels.

What the future holds for gliptins.

Gliptins have revolutionised the treatment of Type 2 Diabetes Mellitus, addressing the hyperglycemia through its effects on the alpha and beta cells of the pancreas. In this article,we review the extra-glycemic effects of gliptins on central nervous system, cardiovascular biology and the bone health and concerns regarding pancreatitis and pancreatic cancer.