Optimal use of once weekly icodec insulin in type-2 diabetes: An updated meta-analysis of phase-2 and phase-3 randomized controlled trials.

BACKGROUND: Previously published meta-analysis have analysed data from 3 small phase-2 randomized controlled trials (RCTs). Since then, 5 big phase-3 RCTs have been published on use of icodec in type-2 diabetes (T2D). This updated systematic review aimed to establish the best practices and safety of icodec in T2D. METHODS: Databases were searched for RCTs involving T2D patients receiving icodec. Primary outcome was change in HbA1c. Secondary outcomes were alterations in glycaemic parameters and adverse events. RESULTS: Data from 8 studies (4317 patients) was analysed. Compared to other basal insulins, icodec had comparable HbA1c lowering at 16-weeks [MD-0.19 %(95%CI: 0.58-0.20); P = 0.35; I2 = 92 %], better HbA1c lowering at 26-weeks [MD-0.19 %(95%CI: 0.35-0.013); P = 0.02; I2 = 94 %] and 52-weeks [MD -0.28 %(95%CI: 0.45-0.12); P = 0.0008; I2 = 100 %]. Percentage of participants achieving HbA1c<7 % with icodec was higher at 16-weeks [OR2.37(95%CI:1.05-5.35); P = 0.04], comparable at 26-weeks [OR1.38(95%CI:0.91-2.11); P = 0.13; I2 = 80 %], and higher at 52-weeks [OR1.55(95%CI:1.30-1.85); P < 0.00001; I2 = 0 %]. Percentage of participants achieving HbA1c<7 % without level 2/3 hypoglycaemia was higher with icodec at 26-weeks [OR1.37(95%CI:1.10-1.71); P = 0.004; I2 = 28 %] and 52-weeks [OR1.48(95%CI:1.24-1.77); P < 0.001; I2 = 0 %]. At 26-weeks, injection-site reactions was higher with icodec [OR1.95(95%CI:1.06-3.56); P = 0.03; I2 = 0 %]. At 26-weeks level-1 hypoglycemia [OR1.40(95%CI:1.02-1.94); P = 0.04; I2 = 58 %], but not level-2/3 hypoglycaemia was higher with icodec. Subset analysis revealed increased occurrence of level-1 [OR 4.19 (95 % CI: 3.20-5.50); P < 0.00001] and level-2 [OR 3.97 (95 % CI: 3.04-5.18); P < 0.00001] hypoglycaemia in participants who received one-time additional 50 % icodec loading dose as compared to those who did not. At 26-weeks, weight-gain was significantly higher with icodec [MD0.61 kg(95%CI:0.38-0.84); P < 0.00001; I2 = 98 %]. CONCLUSION: Icodec insulin is well tolerated with glycaemic efficacy similar to all other available basal insulins.

Efficacy and Safety of Novel Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone in the Management of Diabetic Kidney Disease: A Meta-analysis.

Background: Data are scant on use of finerenone in diabetic kidney disease (DKD). We undertook this meta-analysis to address this knowledge gap. Methods: Electronic databases were searched for randomized controlled trials (RCTs) involving diabetes patients receiving finerenone compared to controls. The primary outcome was changes in urine albumin-creatinine ratio (UACR). Secondary outcomes were time to kidney failure (decline in GFR by >40% from baseline over 4 weeks), time to end-stage kidney disease, hospitalization for any cause, death and adverse events reported. Results: From initially screened 79 articles, data from 7 RCTs involving 13,783 patients were analyzed (3 in active control group [ACG] defined as having eplerenone/spironolactone as active comparator; 4 in passive control group [PCG] defined as having placebo as controls). Patients receiving finerenone had greater percentage lowering of UACR from baseline as compared to PCG [MD23.82% (95%CI: -24.87 to -22.77); P < 0.01; I 2 = 96%] at 90 days, after 2 years [MD 37.9% (95%CI: -38.09 to -37.71); P < 0.01] and 4 years [MD 25.20%(95%CI: -25.63 to -24.77);P < 0.01] of treatment. Patients receiving finerenone has lower chance of >40% decline in GFR (OR 0.83 [95%CI: 0.75 to 0.92];P < 0.01; I 2 = 0%). Patients receiving finerenone had lower occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure, as compared to placebo/eplerenone (OR0.86 [95%CI: 0.78 to 0.95]; P = 0.003; I 2 = 0%). TAEs was similar (RR0.97 [95%CI: 0.88-1.07]; P = 0.56; I 2 = 0%), but SAEs significantly lower (RR0.91 [95%CI: 0.84 to 0.97]; P < 0.01; I 2 = 0%) in finerenone-group compared to controls. Conclusion: This meta-analysis provides reassuring data on beneficial impact of finerenone in reducing UACR and GFR decline as compared to placebo. We still lack head-to-head comparison of renal outcomes of finerenone vs eplerenone/spironolactone in DKD.

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis.

BACKGROUND & AIMS: Pooled systematic analysis of safety and efficacy data of trelagliptin in type-2 diabetes (T2DM) is lacking. We undertook this meta-analysis to address this issue. METHODS: Electronic databases were searched for RCTs involving people with T2DM receiving trelagliptin in study arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in pre and post-meal glucose levels, glycaemic targets, lipid parameters and adverse events. RESULTS: From initially screened 63 articles, data from 6 RCTs involving 981 patients was analysed [3 in active control group (ACG) defined as having alogliptin, sitagliptin, linagliptin, teneligliptin, anagliptin or vildagliptin as active comparator; 2 in passive control group (PCG) defined as having placebo as controls; 1 study had both ACG and PCG]. HbA1c reduction by trelagliptin was comparable to ACG [MD 0.06% (95% CI: -0.03 - 0.16); P = 0.20; I2 = 0%], but superior to PCG [MD -0.54% (95% CI: -0.64 to -0.44); P < 0.01; I2 = 22%]. Fasting blood glucose lowering with trelagliptin was inferior to ACG [MD +6.98 mg/dl (95%CI: 2.55-11.42); P = 0.002; I2 = 0%], but superior to PCG [MD -6.11 mg/dl (95%CI: -12.00 to -0.23); P = 0.04; I2 = 54%]. Glycated albumin lowering was similar to ACG [MD 0.03% (95%CI: -0.47 - 0.53); P = 0.92; I2 = 0%], but superior to PCG [MD -2.31% (95% CI: -2.86 to -1.76); P < 0.01; I2 = 0%]. Treatment-emergent adverse events [Risk ratio (RR) 1.18 (95%CI:0.63-2.21); P = 0.59; I2 = 19%] and severe adverse events [RR 1.75 (95%CI: 0.90-3.40); P = 0.10; I2 = 0%] were comparable among groups. CONCLUSION: Once weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM.

Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis

No meta-analysis is available which has analysed the role of letrozole in constitutional delay in growth and puberty (CDGP). Electronic databases were searched for randomized controlled trials (RCTs) involving children with CDGP receiving letrozole. Primary outcomes were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age (BA), hormonal markers of puberty, bone mineral density and side-effects. One hundred-thirty articles were reviewed, from which seven RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63 cm (95% confidence interval (CI): 3.90-5.36); p<0.01; I2=0%] but not testosterone [MD: 2.21 cm (95% CI: -1.71-6.16); p=0.27; I2=98%] with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo [MD: 4.80 mL (95% CI: 0.57-9.03); p=0.03] and testosterone [MD: 3.36 mL (95% CI: 0.58-6.75); p=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole tended to be superior to testosterone [MD: -0.84 years (95% CI: 2.83-8.18); p=0.06; I2=0%] with regards to slowing in BA progression after 12-months use. Serum luteinizing hormone, follicle stimulating hormone, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, including spinal deformities, were noted with letrozole. Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and may be better at delaying bone-age progression.

Expert opinion on the preoperative medical optimization of adults with diabetes undergoing metabolic surgery.

Diabetes mellitus (DM) and obesity are interrelated in a complex manner, and their coexistence predisposes patients to a plethora of medical problems. Metabolic surgery has evolved as a promising therapeutic option for both conditions. It is recommended that patients, particularly those of Asian origin, maintain a lower body mass index threshold in the presence of uncontrolled DM. However, several comorbidities often accompany these chronic diseases and need to be addressed for successful surgical outcome. Laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the most commonly used bariatric procedures worldwide. The bariatric benefits of RYGB and LSG are similar, but emerging evidence indicates that RYGB is more effective than LSG in improving glycemic control and induces higher rates of long-term DM remission. Several scoring systems have been formulated that are utilized to predict the chances of remission. A glycemic target of glycated hemoglobin < 7% is a reasonable goal before surgery. Cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, nutritional, and psychological optimization of surgical candidates improves perioperative and long-term outcomes. Various guidelines for preoperative care of individuals with obesity have been formulated, but very few specifically focus on the concerns arising from the presence of concomitant DM. It is hoped that this statement will lead to the standardization of presurgical management of individuals with DM undergoing metabolic surgery.

Effect of yoga on glycemia and lipid parameters in type-2 diabetes: a meta-analysis.

PURPOSE: Prior systematic reviews on yoga and diabetes have given conflicting results. They have been limited by inclusion of uncontrolled unblinded single group observational studies. No reviews are available which have used the Cochrane methodology and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. This meta-analysis evaluated the efficacy of yoga on glycaemia and lipids in T2DM using the Cochrane methodology and GRADE approach. METHODS: Major repositories were searched to pick randomized controlled trials involving T2DM patients receiving yoga. Primary outcome was to evaluate changes in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c). Secondary outcomes were to evaluate changes in post-prandial plasma glucose (PPG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Sub-group analysis involving people undergoing structured exercise regimen (SER) versus those undergoing standard diabetes care in controls was done. RESULTS: Data from 13 studies involving 1440 patients were analysed. Compared to controls, individuals doing yoga had significantly lower FPG [mean difference (MD) -17.22 mg/dl (95% CI: -26.19 - -8.26 mg/dl); p < 0.01; considerable heterogeneity (CH); low certainty of evidence (LCE)], PPG [MD -27.77 mg/dl (95% CI: -35.73 - -19.81 mg/dl); p < 0.01; low heterogeneity; moderate certainty of evidence (MCE)], TC [MD -19.48 mg/dl (95% CI: -31.97 - -6.99 mg/dl); p < 0.01; CH; LCE], triglycerides [MD -12.99 mg/dl (95% CI: -23.74 - -2.25 mg/dl); p < 0.01; CH; LCE], LDL-C [MD -11.71 mg/dl (95% CI: -17.49 - -5.93 mg/dl); p < 0.01; I2 = 69% CH; LCE] and significantly higher HDL-C [MD 4.58 mg/dl (95% CI: 3.98-5.18 mg/dl); p < 0.01; low heterogeneity; MCE]. On sub-group analysis, where yoga was compared to SER, FPG was significantly lower in yoga group. CONCLUSION: Yoga improves glycaemia and lipid parameters in T2DM with additional benefits seen both in people doing/not doing structured exercise. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00751-0.

Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis.

Background: Till date, there is no Cochrane meta-analysis available which has analyzed efficacy and safety of tirzepatide in type-2 diabetes. This meta-analysis was undertaken to address this knowledge gap. Methods: Electronic databases were searched for randomized controlled trials (RCTs) involving people with diabetes receiving tirzepatide compared to a placebo/active comparator. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood-glucose, glycemic targets, weight, lipids, and adverse events. Results: From 34 articles initially screened, data from six RCTs involving 3484 patients were analyzed. Over 12-52 weeks, individuals receiving tirzepatide had significantly greater lowering of HbA1c [mean difference (MD) = -0.75% (95% confidence interval (CI): -1.05 to -0.45); P < 0.01; I 2 = 100%], fasting glucose [MD = -0.75 mmol/L (95% CI: -1.05 to- -0.45); P < 0.01; I 2 = 100%], 2-h post-prandial-glucose [MD = -0.87 mmol/L (95% CI: -1.12 to -0.61); P < 0.01; I 2 = 99%], weight [MD = -8.63 kg (95% CI: -12.89 to -4.36); P < 0.01; I 2 = 100%], body mass index [MD = -1.80 kg/m2 (95% CI: -2.39 to -1.21); P < 0.01; I 2 = 99%], and waist circumference [MD = -4.43 cm (95% CI: -5.31 to -3.55); P < 0.01; I 2 = 95%] as compared to dulaglutide, semaglutide, degludec, or glargine. Patients receiving tirzepatide had higher odds of achieving HbA1c <6.5% compared to active controls [odds ratio (OR) = 4.39 (95% CI: 2.44-7.92); P < 0.01; I 2 = 90%]. Tirzepatide use had significantly higher odds of weight loss >5% [OR = 19.18 (95% CI: 2.34-157.17); P < 0.01; I 2 = 99%], >10% [OR = 21.40 (95% CI: 2.36-193.94); P < 0.01; I 2 = 98%], and >15% [OR = 32.84 (95% CI: 2.27-474.33); P = 0.01; I 2 = 96%] compared to active-control group. Treatment-emergent adverse events [risk ratio (RR) = 1.43 (95% CI: 1.14-1.80); P < 0.01; I 2 = 40%] and severe adverse events [RR = 1.00 (95% CI: 0.64-1.57); P = 1.00; I 2 = 49%] were not different. High data heterogeneity and the presence of publication bias limits the grading of current data from "moderate to low." Conclusion: Tirzepatide has impressive glycemic efficacy and weight-loss data over 1-year clinical use. The need for higher grade, long-term efficacy, and safety data remains.

Cardiometabolic vigilance in COVID-19 and resource husbandry in resource-challenged times: Clinical practice- based expert opinion.

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.

Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis.

BACKGROUND AND AIMS: Saroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia. METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)]. RESULTS: Following 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: -123.67 to -19.66 mg/dl); P < 0.01; I2 = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: -84.55-9.79 mg/dl; P = 0.12; I2 = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: -44.13 to -5.09 mg/dl); P = 0.01; I2 = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: -33.1-6.10 mg/dl; P = 0.18; I2 = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04-0.21 mg/dl); P < 0.01; I2 = 29% (low heterogeneity); high certainty of evidence]. CONCLUSION: This meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.

Endocrine and Metabolic Manifestations of Snakebite Envenoming.

Snakebite envenoming is a neglected, public health problem in tropical and subtropical regions. Local tissue necrosis, neurotoxic, and hemo-vasculotoxic effects are well-recognized features, whereas the endocrine and metabolic derangements are not as well known. In addition to contributing to morbidity, some of these manifestations can be potentially life-threatening if not recognized early. The most prominent endocrine manifestation is hypopituitarism (HP), which can manifest acutely or remain asymptomatic and present years later. Unexplained recurrent hypoglycemia and refractory hypotension are early clinical clues to suspect corticotroph axis involvement in acute settings. Chronic pituitary failure may present, like Sheehan's syndrome, several years after the bite. The occurrence of acute kidney injury, capillary leak syndrome, and disseminated intravascular coagulation are predictors of HP. Adrenal hemorrhages are documented in autopsy series; however, primary adrenal insufficiency is very rare and confounded by the presence of HP. Hyponatremia, hypokalemia or hyperkalemia, and dysglycemia can occur, but the mechanisms involved are only partially understood. Awareness, a high index of suspicion, correct interpretation of hormonal parameters, and timely treatment of these abnormalities can be lifesaving.

Vitamin B12 Deficiency is Endemic in Indian Population: A Perspective from North India.

BACKGROUND: Vitamin B12 deficiency is believed to be widespread in Indian population. However, more data is needed to fuel a meaningful debate on preventive and therapeutic strategies. AIMS AND OBJECTIVES: Objective of the current study is to evaluate status of vitamin B12 levels in people from a tier 3 city and among people living in an urban area with or without diabetes. SETTINGS AND DESIGN: Retrospective, cross-sectional study. METHODOLOGY: Data captured in electronic medical records (EMR) of an endocrine practice and from a diagnostic laboratory was analysed. STATISTICAL ANALYSIS USED: Statistical analysis was done using open source software "Jamovi". RESULTS: Prevalence of vitamin B12 deficiency (Vitamin B12 levels <200 pg/ml) in tier 3 city was 47.19% (n = 267). From an urban endocrine practice, database of 11913 patients was searched for reports of vitamin B12 levels. Prevalence of vitamin B12 deficiency was 37.76% in people with pre-diabetes (n = 92), 31.23% in people with endocrine problems other than diabetes and pre-diabetes (n = 285) and 18.25% in people with diabetes (n = 378). Tier 3 city population had significantly lower vitamin B12 levels than people living in an urban area and attending an endocrine clinic. Vitamin B12 levels were significantly higher in people with diabetes as compared to people with other endocrine problems. CONCLUSION: Prevalence of vitamin B12 deficiency is 47% in north Indian population. People with diabetes have higher vitamin B12 levels than general population though still have high prevalence of deficiency. This data shows that Vitamin B12 deficiency is widespread in Indian population.

BE-SMART (Basal Early Strategies to Maximize HbA1c Reduction with Oral Therapy): Expert Opinion.

The past three decades have seen a quadruple rise in the number of people affected by diabetes mellitus worldwide, with the disease being the ninth major cause of mortality. Type 2 diabetes mellitus (T2DM) often remains undiagnosed for several years due to its asymptomatic nature during the initial stages. In India, 70% of diagnosed diabetes cases remain uncontrolled. Current guidelines endorse the initiation of insulin early in the course of the disease, specifically in patients with HbA1c > 10%, as the use of oral agents alone is unlikely to achieve glycemic targets. Early insulin initiation and optimization of glycemic control using insulin titration algorithms and patient empowerment can facilitate the effective management of uncontrolled diabetes. Early glucose control has sustained benefits in people with diabetes. However, insulin initiation, dose adjustment, and the need to repeatedly assess blood glucose levels are often perplexing for both physicians and patients, and there are misconceptions and concerns regarding its use. Hence, an early transition to insulin and ideal intensification of treatment may aid in delaying the onset of diabetes complications. This opinion statement was formulated by an expert panel on the basis of existing guidelines, clinical experience, and economic and cultural contexts. The statement stresses the timely and appropriate use of basal insulin in T2DM. It focuses on the seven vital Ts-treatment initiation, timing of administration, transportation and storage, technique of administration, targets for titration, tablets, and tools for monitoring.Funding: Sanofi.

Pre ketogenic diet counselling.

This communication describes the aims and aspects of counseling prior to start of a ketogenic diet (KD). It uses a reader-friendly bio-psycho-social format to list and structure the various components of pre ketogenic diet counseling. These include strength mapping, risk and benefit explanation, and understanding the patient's selfcare responsibilities. This simple, yet practical discussion fills a major void in current literature, which seems to have ignored patient centred counseling strategies for KD in persons with obesity and diabetes.

Height Velocity in Apparently Healthy North Indian School Children.

OBJECTIVE: Linear growth is best estimated by serial anthropometric data or height velocity (HV). In the absence of recent data on growth velocity, we undertook to establish normative data in apparently healthy North Indian children. MATERIALS AND METHODS: Prospective longitudinal study in a representative sample of 7710 apparently healthy children, aged 3-17 years from different regions of Delhi. Height was measured at baseline and at 12 months while pubertal examination was performed at baseline in a subset of children. RESULTS: The data on HV and puberty were available in 5635 participants (73.08%; 2341 boys and 3294 girls) and 1553 participants (622 boys; and 931 girls), respectively. The mean peak height velocity (PHV) was 7.82 ± 2.60 cm in boys seen at 12-12.9 years and 6.63 ± 1.81 cm in girls at 10-10.9 years Although late maturing boys had a greater HV than early or normal maturers, it did not vary with the age of pubertal maturation in girls. HV correlated with parental height in prepubertal boys, girls, and pubertal boys (P < 0.01) while no correlation was seen in girls. CONCLUSIONS: The study presents normal height velocities in North Indian children. A secular trend was observed in achieving PHV in both boys and girls.

Neutrophil-lymphocyte Ratio is a Novel Reliable Predictor of Nephropathy, Retinopathy, and Coronary Artery Disease in Indians with Type-2 Diabetes.

BACKGROUND AND AIMS: Neutrophil-lymphocyte ratio (NLR) has been suggested to be a predictor of coronary artery disease (CAD), and end-organ damage in type-2 diabetes mellitus (T2DM). Similar data are lacking from Indians with T2DM. Hence, this study aimed to evaluate the role of NLR as a predictor of microvascular complications and CAD in T2DM. SUBJECTS AND METHODS: Consecutive T2DM patients attending the outpatient services of 2 different hospitals, who gave consent, underwent clinical, anthropometric evaluation, and evaluation for the occurrence of retinopathy, nephropathy, neuropathy, and CAD. RESULTS: A total of 298 patients were screened of which 265 patients' data were analyzed. Occurrence of hypertension, neuropathy, nephropathy, retinopathy, and CAD was 12.8%, 18.5%, 41.5%, 62.3%, and 3.8%, respectively. Patients in higher NLR quartiles had significantly higher diabetes duration, occurrence of nephropathy, albuminuria, retinopathy, CAD and lpwer glomerular filtration rate. Patients with more microvascular complications had significantly longer diabetes duration, blood pressure, NLR, creatinine, and urine albumin excretion. Binary logistic regression revealed NLR followed by body mass index were best predictors of microvascular complications. NLR had areas under the receiver operating characteristic curve (AUC) of 0.888 (95% CI: 0.848-0.929; P < 0.001), 0.708 (95% CI: 0.646-0.771; P < 0.001), and 0.768 (95% CI: 0.599-938; P = 0.004) in predicting albuminuria, retinopathy, and CAD, respectively. NLR of 2.00 had sensitivity and specificity of 86.4% and 69% in predicting albuminuria; sensitivity and specificity of 64.2% and 63% in predicting retinopathy; sensitivity and specificity of 80% and 47.1% in predicting CAD. CONCLUSION: NLR is inexpensive, easy to use, reliable predictor of nephropathy, retinopathy, and CAD in Indian T2DM.

Pubertal Onset in Apparently Healthy Indian Boys and Impact of Obesity.

OBJECTIVE: Primary - to determine the age of pubertal onset in Indian boys. Secondary - (a) to assess the impact of obesity on pubertal timing, (b) to assess the relationship between gonadotropins and puberty. DESIGN: Cross-sectional. SETTING: General community-seven schools across New Delhi. PARTICIPANTS: Random sample of 1306 school boys, aged 6-17 years. MATERIALS AND METHODS: Anthropometric measurement for weight and height and pubertal staging was performed for all subjects. Body mass index (BMI) was calculated to define overweight/obesity. Serum luteinizing hormone (LH), follicle stimulating hormone, and serum testosterone were measured in every sixth subject. MAIN OUTCOME MEASURE: Age at pubertal onset-testicular volume ≥4 mL (gonadarche) and pubic hair Stage II. RESULTS: Median age of attaining gonadarche and pubarche was 10.41 years (95% confidence interval [CI]: 10.2-10.6 years) and 13.60 (95% CI: 13.3-14.0 years), respectively. No significant difference in the age of attainment of gonadarche was observed in boys with normal or raised BMI, though pubarche occurred 8 months earlier in the latter group. Serum gonadotropins and testosterone increased with increasing stages of puberty but were unaffected by BMI. Serum LH level of 1.02 mIU/mL and testosterone level of >0.14 ng/mL showed the best prediction for pubertal onset. CONCLUSION: The study establishes a secular trend of the age of onset of puberty in Indian boys. Pubarche occurred earlier in overweight/obese boys. The cutoff levels of serum LH and testosterone for prediction of pubertal onset have been established.

Perceptions about Training during Endocrinology Residency Programs in India over the Years: A Cross-sectional Study (PEER India Study).

BACKGROUND: Residents' perception on quality of endocrinology training in India is not known. This study aimed to evaluate the perceptions about endocrinology residency programs in India among current trainees as compared to practicing endocrinologists. METHODS: Trainees attending a preconference workshop at the annual conference of Endocrine Society of India (ESI) were given a questionnaire designed to evaluate their perceptions on their training. These evaluated the reasons for choosing endocrinology, their experiences during residency, and career plans. Practicing endocrinologists attending ESICON with at least 5-year experience were evaluated as controls. RESULTS: Questionnaires from 63 endocrine trainees and 78 practicing endocrinologists were analyzed. Endocrinology is perceived to be the super-specialty with the best quality of life (QOL) but fair with regard to financial remuneration. Among current trainees, 61.89%, 31.74%, and 34.91% are satisfied with training in clinical endocrinology, laboratory endocrinology, and clinical/translational research, respectively. The corresponding figures for practicing endocrinologists are 71.78%, 25.63%, and 30.75%, respectively. Exposure to national endocrinology conferences during their endocrinology residency was adequate. However, exposure to international endocrinology conferences, research publications, project writing, and grant application are limited. Laboratory endocrinology is rated as the most neglected aspect during endocrine residency. Most of the trainees want to establish their own clinical practice in the long run. Very few trainees (17.46%) wish to join the medical education services. CONCLUSION: There is a good perception of QOL in endocrinology in spite of average financial remuneration. There is dissatisfaction with the quality of training in laboratory endocrinology and clinical research. Very few endocrine trainees consider academics as a long-term career option in India.

A 2016 clinical practice pattern in the management of primary hypothyroidism among doctors from different clinical specialties in New Delhi.

BACKGROUND: This study aimed to document practices in managing hypothyroidism among doctors in New Delhi, with special focus on subclinical hypothyroidism, pregnancy, and old age, and to compare it with global practices. METHODS: During an academic program attended by 394 doctors, all participants were given a questionnaire designed based on thyroid practices survey done by Burch et al. to evaluate the practice patterns. Questions were based on evaluating doctor's preferred choices in diagnosis, therapy, and follow-up of hypothyroidism in different scenarios. RESULTS: Responses from 308 questionnaires (general physicians [n = 204], obstetricians [n = 51], pediatricians [n = 27], surgeons [n = 12], endocrinologists [n = 10], and others [n = 4]) were analyzed. In the evaluation of 52-year-old female patient with primary hypothyroidism, 52% doctors would prefer thyroid ultrasonography, comparable to global rates. Nearly 96.1% doctors would have initiated levothyroxine, with a large majority of doctors (83.77%) preferred using branded levothyroxine. About 58.74% doctors preferred gradual restoration of euthyroidism. Levothyroxine dose of 25 mcg was the most preferred increment dose (46.07%) during follow-up, with 6 weekly being the most frequent dose adjustment frequency (41.57%). Most preferred target thyroid-stimulating hormone (TSH) in the 52-year-old female patient was 2.5-4.99 mU/L (63.96%), 25-year-old female patient was 1-2.49 mU/L (53.90%), and in 85-year-old female was 2.5-4.99 mU/L (45.45%). Only 68% of doctors in our study preferred keeping TSH <2.5 mU/L during the first trimester of pregnancy, in contrast to global trends of 95% (P < 0.001). CONCLUSION: There was a disproportionately high use of ultrasonography in hypothyroidism management, near exclusive preference for branded levothyroxine, widespread use of age-specific TSH targets, and low threshold for treating mild thyroid failure, a highly variable approach to both rates and means of restoring euthyroidism for overt primary hypothyroidism. There is a need for spreading awareness regarding TSH targets in pregnancy.

Age of Onset of Puberty in Apparently Healthy School Girls from Northern India.

OBJECTIVE: To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. DESIGN: Cross-sectional. SETTING: Seven schools across Delhi, India. PARTICIPANTS: 2010 school girls, aged 6-17 years. METHODS: Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by status quo method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. MAIN OUTCOME MEASURES: Age at thelarche and menarche analyzed for entire cohort and stratified based on body mass index. RESULTS: Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. CONCLUSION: The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls.

Diagnosis and management of classical congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis.