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Diabetes mellitus is a syndrome characterized by hyperglycemia and dyslipidemia; and is associated with various systemic complications including acute metabolic emergencies and chronic complications, which includes microvascular and macrovascular manifestations. Coronary artery diseases are the major causes of morbidity and mortality. Various studies have convincingly demonstrated that managing hyperglycemia adequately is important for controlling diabetic complications, but macrovascular complications have not shown as significant reduction as have microvascular diseases. The cardiac safety of various anti-diabetic agents available to us also vary, which suggests that both euglycemia per se, as well the agent used to achieve it, are important considerations for cardiovascular safety. The Food and Drugs Administration of the United States of America has now stipulated that all anti-diabetic medications must undergo cardio-vascular outcome trials to prove cardiac safety before they are approved for use. Most currently available anti-diabetics are neutral on the heart, and may be continued safely in patients with chronic stable coronary artery disease (CAD). However, recent data from cardio-vascular outcome trials involving SGLT2-inhibitors and GLP1R-analogs demonstrate impressive cardiac safety data. Insulin still remains the agent of choice during recent acute coronary events and critical-care management.

Aim: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management., Background: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations., Review Results: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most., Conclusion: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

Aim: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs)., Background: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed., Review Results: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required., Conclusion: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: 5alpha-Reductase deficiency (5RD) is an uncommon autosomal recessive disorder of sexual differentiation. It results from impaired conversion of testosterone to dihydrotestosterone due to mutations in the steroid 5alpha-reductase type 2 gene (SRD5A2). Mutations in SRD5A2 have not been previously reported in Indian patients with 5RD., Aim: To delineate the clinical features and mutations in the SRD5A2 gene in Indian patients with 5RD., Patients and Methods: The SRDSA2 gene was sequenced in two unrelated patients with elevated testosterone/dihydrotestosterone ratio and in one patient with classical clinical features and virilization at puberty (in whom the ratio could not be measured due to prior gonadectomy). The prevalence of SRD5A2 mutations was also studied in 52 healthy ethnic control subjects by PCR-RFLP., Results: Two patients, both from the north Indian state of Uttar Pradesh, carried the homozygous missense mutation p.R246Q in exon 5. Parents of both probands were heterozygous for the mutation. The mutation was absent in 52 control subjects. The third patient, with severe perineoscrotal hypospadias and micropenis, was detected to have a novel heterozygous missense mutation p.Q56H, as well as the homozygous polymorphism p.V89L, both in exon 1. The p.Q56H mutation was absent in 52 control subjects., Conclusion: p.R246Q is a common SRD5A2 mutation in 5RD patients from the Indian subcontinent.

Objective: To assess the suitability of recently published reference anthropometric data for evaluation of the growth of children in our region., Setting: Referral Pediatric Endocrinology Clinic in tertiary level care hospital., Subjects: 280 normal school children and 155 children referred for growth retardation to the clinic in 1993 and 1994., Methods: Heights of school children were plotted on growth charts created from recently published reference growth data of children from high socioeconomic group families. The case records of 155 children referred for growth evaluation were retrospectively analyzed for (i) etiology of short stature, (ii) height percentile based on previously used Indian Council of Medical Research (ICMR) references, and (iii) height percentile and standard deviation scores based on the new references., Results: 93% of school children fell above and 7% below the 5th centile of the new height references. Of the 129 clinic children diagnosed to have growth retardation, 128 fell below the 5th centile of the new references. However, 38 of these (29.5%) fell above the 5th centile of ICMR references. These included patients with pathological causes of short stature. Twenty four of 26 children labelled as having no growth problem fell above the 5th centile of new reference data., Conclusions: The 5th height centile of new reference data from high socioeconomic group children is an appropriate cut off below which to evaluate children for short stature in our region. It will allow earlier identification and treatment than the hitherto used ICMR percentiles, and yet is not expected to result in over investigation of normal children.

Background: Extrahepatic portal vein obstruction has been shown to cause growth retardation in children, though literature is scant. No information is available regarding the cause of growth retardation in these patients., Methods: To document the presence of growth retardation in this disease, we studied growth and nutrition in 33 consecutive prepubertal patients. Anthropometry, fasting growth hormone, and insulin-like growth factor I levels were compared in 22 well-nourished patients from this group with 35 age-matched well-nourished controls., Results: Mean +/- SD height standard deviation score of well-nourished patients (-1.88 +/- 1.33) was significantly below that of the controls (-1.06 +/- 0.64, p < 0.01). Patients also had significantly lower midarm muscle circumference z scores (-2.65 +/- 1.09) than controls (-1.17 +/- 1.09, p < 0.0001), though triceps skinfold thickness z scores were comparable in the two groups (-1.06 +/- 0.68 vs -1.24 +/- 0.79, p = NS). Insulin-like growth factor I z scores were significantly lower in patients (-1.48 +/- 0.88) than in controls (-0.49 +/- 1.09, p < 0.001), whereas basal growth hormone was significantly higher in patients (4.60 +/- 3.70 mIU/L) compared with controls (2.66 +/- 0.82, p < 0.01)., Conclusion: Extrahepatic portal vein obstruction in children leads to growth retardation. Anthropometric and preliminary hormonal evaluation suggest resistance to the action of growth hormone as a possible mechanism.

Tropical calcific pancreatitis (TCP) is a variant of chronic pancreatitis, occurring only in developing countries. It frequently leads to diabetes at a young age. To determine the pathogenesis of glucose intolerance, beta-cell function and insulin sensitivity were measured in 11 TCP patients with normal glucose tolerance (TCP-NGT), six TCP patients with mild hyperglycemia [TCP-DM] median fasting plasma glucose, 6.1 mmol/L), and 16 healthy control subjects. The technique of continuous infusion of glucose with model assessment (CIGMA) was used to calculate beta-cell function (%B) and insulin sensitivity (%S), based on plasma glucose and insulin levels achieved after an intravenous infusion of glucose. %S was similar in both groups of TCP patients and controls. In contrast, %B was significantly lower in TCP-DM patients (median, 53; interquartile range, 41 to 62) compared with controls (90; 65 to 143; P < .01) and with TCP-NGT patients (119; 91 to 159; P < .01). TCP-NGT and control subjects had similar beta-cell function. Among patients with TCP, %B negatively correlated with the duration of pancreatitis (r = -.63, P < .05). Our results suggest that patients with TCP develop diabetes due to a diminution in beta-cell function, and that insulin resistance does not play a significant role in its pathogenesis.

We have used the stopped-flow indicator dye method to measure proton release and product formation simultaneously in the initial transient-state portion of the glutamate dehydrogenase-catalyzed oxidative deamination of L-glutamate. We observe a measurably slow release of a proton from the enzyme-NADP-L-glutamate complex. This proton release precedes the hydride transfer step, as indicated by the distinct lag in the product formation signal. We show that the proton release step corresponds to an obligatory intermediate in the reaction sequence. We also find that compounds which are competitive inhibitors of L-glutamate are capable of inducing this phenomenon. We prove that this unanticipated prehydride transfer event cannot be due to the release of an alpha-amino group proton from the substrate.