Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis.

BACKGROUND: Once-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials. METHODS: Seven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in "estimated differences in mean (with 95% CI)." For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI). RESULTS: Analyzing against the nonicodec comparators together, the "estimated mean changes" in HbA1c and fasting plasma glucose favoring icodec were -0.22% (-0.35, -0.10) and -1.59 mg% (-9.26, 6.08) respectively. The "estimated mean increment" in weight for icodec was 0.64 kg (0.61, 0.67). The "estimated mean percentage" increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec. CONCLUSION: Once-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR).

Simplifying Type 2 DM Care with Linagliptin: A Position Paper.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) is raising dramatically both internationally and in India. It is often observed that multiple therapies or combinations of different drugs are usually required to successfully control hyperglycemia in patients with T2DM. To facilitate effective control of glucose levels, many new agents have been developed over the past few years. MATERIALS AND METHODS: Multiple Advisory Board Meetings were conducted with 87 leading key opinion leaders (KOLs) from diabetes specialty PAN India to understand the simplicity aspect of linagliptin therapy in T2DM patients. DISCUSSION: Linagliptin is a xanthine-based, non-peptidomimetic, selective dipeptidyl peptidase 4 (DPP-4) inhibitor with a different pharmacological profile when compared to other DPP-4 inhibitors already available in India. It is known to decrease the risk of hypoglycemia compared to sulphonylurea (SU), is weight neutral, and no dose modification is required over a broad range of patient populations. This consensus paper discusses the clinical efficacy of DPP-4 inhibitors and linagliptin in T2DM. It also highlights the evidence for the safety of linagliptin in T2DM patients with renal impairment (RI), cardiovascular (CV) risk, and heart failure (HF). CONCLUSION: Linagliptin therapy is simplifying the management of T2DM with good efficacy and its use across a wide range of patients without any dose modification.

Different Sodium-Glucose Cotransporter-2 Inhibitors: Can They Prevent Death?

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcome trials (CVOTs) demonstrate cardiovascular (CV) safety and benefits. Some dedicated randomized controlled trials (RCTs) demonstrate benefit in terms of renal outcomes and hospitalization due to heart failure (HF). RCTs report differences in the secondary outcomes with respect to mortality (CV and/or all-cause). We undertook a meta-analysis of all SGLT2is for which in addition to CVOT, HF outcome/renal outcome studies are available to establish whether individual SGLT2is were able to prevent death. METHODS: We included available event-driven randomized, placebo-controlled CVOTs and dedicated RCTs of SGLT2is exploring renal outcomes and HF. We included 3 trials of empagliflozin, 3 of dapagliflozin, 2 of canagliflozin, and 2 of sotagliflozin. The efficacy outcomes included all-cause mortality and CV mortality. Hazard ratios (HRs) with 95% CIs were pooled for individual molecules. RESULTS: The HR for all-cause mortality including all trials was 0.86 (0.80-0.93). The HRs for all-cause mortality in empagliflozin (N = 16 738), dapagliflozin (N = 26 208), canagliflozin (N = 14 543), and sotagliflozin (N = 11 806) were 0.86 (0.69-1.08), 0.83 (0.72-0.97), 0.86 (0.75-0.97), and 0.95 (0.81-1.11), respectively. The HR for CV mortality including all trials was 0.85 (0.78-0.92). The HRs for CV mortality in empagliflozin, dapagliflozin, sotagliflozin, and canagliflozin were 0.81 (0.63-1.03), 0.88 (0.78-1.00), 0.89 (0.74-1.07), and 0.84 (0.72-0.98), respectively. CONCLUSION: SGLT2is as a class reduce both all-cause mortality and CV mortality. Canagliflozin possibly reduces both all-cause mortality and CV mortality, whereas dapagliflozin may reduce all-cause mortality but not CV mortality. Empagliflozin and sotagliflozin may reduce neither.

Indian Expert Review on Use of Teneligliptin in patients with Diabetes and its Safety and Efficacy (INTENSE).

INTRODUCTION: Management of diabetes in India remains less than satisfactory despite a huge prevalence of type 2 diabetes (T2D). Associated obesity, inadequate lifestyle modifications and burden of treatment costs are certain major issues contributing to inadequate management of diabetes in India. AIM: To evaluate the use of Teneligliptin in patients with diabetes and its safety, efficacy and cost effectiveness especially in Indian patients with T2D. METHODS: A detailed analysis of the best available scientific evidence (clinical trials, meta-analyses and real-world experience) was performed to create an evidence driven understanding of teneligliptin's efficacy, safety and cost effectiveness. Fourteen leading endocrinologists contributed as experts and the modified Delphi process was followed. Evidences and clinical questions were discussed over a series of web and in a live meeting. Final draft was created based on the opinions endorsed by the experts. RESULTS: Teneligliptin is the most commonly used gliptin in India and exhibits pharmacokinetic and pharmacodynamic advantages as well as greater cost effectiveness compared to other gliptins. It has been recognized as an efficacious and well tolerated antidiabetic agent both as monotherapy and in combination based on multiple clinical trials, meta-analyses and real world studies. Teneligliptin as add on therapy to other antidiabetic drugs (OADs) or insulin has provided significant reductions in HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels and is generally well tolerated with low risk of hypoglycemia both in short term and long term. Studies have also proven its efficacy in ameliorating glucose fluctuations, reducing post prandial insulin requirement, increasing active incretin levels and improving pancreatic ß cells function. Efficacy and safety has also been proven in all age groups, all stages of renal disease and mild to moderate hepatic disease. QT prolongation is not seen even with maximum recommended dose of 40 mg/day. CONCLUSION: Teneligliptin has firmly positioned itself as a very important drug in the armamentarium for managing T2D. It offers efficacy, safety and cost-effective therapeutic choice in Indian patients with T2D.

SGLT2 Inhibitors: Effect on Myocardial Infarction and Stroke in Type 2 Diabetes.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently been recommended as preferred agents for management of hyperglycemia in type 2 diabetes, primarily based on their ability to reduce a composite of major cardiovascular adverse events (3-point major adverse cardiovascular events [MACE]), predominantly by reducing cardiovascular death. However, reduction of the individual components, myocardial infarction (MI), or stroke (fatal and nonfatal) events have not been well explored. METHODS: In this meta-analysis, we included data available from cardiovascular outcome trials only, which were event-driven, randomized, and placebo-controlled. Pooled efficacy outcomes included Mantel Haenszel (MH) risk ratio using fixed model (with 95% CI) for fatal and nonfatal MI, stroke, and total MI and stroke. FINDINGS: Data from 4 eligible trials included 42,568 subjects. Total MACE, MI, and stroke were reported in 4176, 2157, and 1288 subjects, respectively. SGLT2is did not significantly reduce either MI or stroke individually or in totality. The MH risk ratio (95% CI) for fatal and nonfatal MI and stroke with different SGLT2is was found to be 0.93 (95% CI, 0.85-1.01) and 1.00 (95% CI, 0.89-1.11), respectively. For total atherosclerotic cardiovascular disease (ASCVD) events, MH risk ratio (95% CI) was 0.95 (95% CI, 0.89-1.02). For all nonfatal ASCVD (combined nonfatal MI and nonfatal stroke), MH risk ratio (95% CI) was 0.94 (95% CI, 0.88-1.02). INTERPRETATION: SGLT2is reduce MACE without any discernable significant reduction of the incidence of MI or stroke (fatal and nonfatal), probably implicating mechanisms unrelated to anti-atherogenic effects.

Glycemic Control and the Weight Benefit of a Daily 7 mg Dose of Oral Semaglutide Versus an Alternate-Day 14 mg Dose of Oral Semaglutide From an Ambulatory Glucose Monitoring Data: A Retrospective Cohort Study From Eastern India.

INTRODUCTION: Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) class of antidiabetic medication. High costs and GI side effects are the major limitations of its widespread use. Some patients who were on a 14 mg dose of oral semaglutide self-prescribed an alternate-day schedule to mitigate GI side effects and to reduce the cost. METHODS: This retrospective observational cohort study evaluates the ambulatory glucose profile (AGP) data, extrapolated glycosylated hemoglobin (HbA1C), and BMI of 11 types of 2 diabetes mellitus (T2DM) while they were on an alternate-day 14 mg dose of oral semaglutide compared to their record while on a daily 7 mg dose. The AGP metrics (time-in-range (TIR), time-below-range (TBR), and time-above-range (TAR)) along with extrapolated HbA1C and BMI were analyzed. Statistical analysis was done using SPSS Statistics version 21.0. RESULTS: No statistically significant difference in the AGP metrics between the AGP profile of a daily 7 mg dose and the AGP profile of an alternate-day 14 mg dose of oral semaglutide was observed. Interestingly, a statistically significant progressive decline in BMI value was observed even on the alternate-day 14 mg dose when compared to the daily 7 mg dose. CONCLUSION: In this small cohort of patients, the metrics of short-term glycemic control and the extrapolated HbA1C values were similar for the daily 7 mg dose versus the alternate-day 14 mg dose of oral semaglutide. BMI showed progressive reduction which was statistically significant even with the alternate-day 14 mg dose of oral semaglutide.

Early Insight Into the Retrospective Data of a Case Series on Type 2 Diabetes Mellitus on Alternate-Day Dosing of Oral Semaglutide: Utopia or Reality?

Introduction Oral semaglutide, with a long half-life of seven days, is the first oral-based peptide drug and is used as an antidiabetic for the reduction of glycosylated hemoglobin (HbA1c). Oral semaglutide, like other glucagon-like peptide-1 receptor agonists (GLP1RAs), is costly and has gastrointestinal (GI) side effects, especially with a 14 mg dose. In the real world, some type 2 diabetes mellitus (T2DM) patients on 14 mg oral dose adopt an alternate-day strategy to minimize unwanted GI symptoms. In this study, we analyzed the ambulatory glucose profile (AGP) data of patients with T2DM who were on 14 mg alternate-day oral semaglutide therapy. Methods This retrospective observational study evaluated the AGP data of 10 patients on alternate-day dosing of 14 mg oral semaglutide. The AGP data over a period of 14 days on a single group of patients were analyzed without any control group or randomization and are presented as a case series. AGP monitoring, using Freestyle Libre Pro (Abbott, Illinois, United States), is a standard operating procedure of the endocrinology department for all T2DM patients who were put on oral semaglutide therapy. The AGP data of the glycemic parameters time-in-range (TIR), time-above-range (TAR), and time-below-range (TBR), were compared between the days when oral semaglutide was consumed (days-on-drug) versus the days when oral semaglutide was not consumed (days-off-drug). The statistical analysis was done with Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp., Armonk, NY). Results We applied the Shapiro-Wilk test (sample size <50) for normality testing; the TIR values of days-on-drug and days-off-drug showed high p values (p =0.285 and 0.109), respectively. This indicated that TIR values days-on-drug and days-off-drug were normally distributed. Although, the distribution of TAR and TBR values days-on-drug and days-off-drug, were not normal as they had small p values (p< 0.05). Hence, further analysis of the paired set of data was done using the Wilcoxon signed-rank test. It revealed no difference in TIR, TAR, and TBR between the two groups (days-on-drug and days-off-drug). Conclusion Throughout the period of observation, the glycemic metrics (TIR, TAR, and TBR) remained steady with a 14 mg alternate-day oral semaglutide regimen.

IDEA Group Consensus Statement on Medical Management of Adult Gender Incongruent Individuals Seeking Gender Affirmation as Male.

Gender-affirming hormone therapy (GAHT) is the most frequent treatment offered to gender-incongruent individuals, which reduces dysphoria. The goal of therapy among gender-incongruent individuals seeking gender affirmation as male is to change their secondary sex characteristics to affect masculine physical appearances. GAHT greatly improves mental health and quality of life among gender incongruent individuals. India-specific guideline for appropriate care for gender-incongruent individuals is almost absent. This document is intended to assist endocrinologists and other healthcare professionals interested in gender incongruity for individuals seeking gender affirmation as male. A safe and effective GAHT regimen aims to effect masculinising physical features without adverse effects. In this document, we offer suggestions based on an in-depth review of national and international guidelines, recently available evidence and collegial meetings with expert Indian clinicians working in this field. Clinicians represented in our expert panel have developed expertise due to the volume of gender incongruent individuals they manage. This consensus statement provides protocols for the hormone prescribing physicians relating to diagnosis, baseline evaluation and counselling, prescription planning for masculinising hormone therapy, choice of therapy, targets for monitoring masculinising hormone therapy, clinical and biochemical monitoring, recommending sex affirmation surgery and peri-operative hormone therapy. The recommendations made in this document are not rigid guidelines, and the hormone-prescribing physicians are encouraged to modify the suggested protocol to address emerging issues.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Characteristics of children and adolescents with newly diagnosed Fibrocalculous pancreatitis diabetes (FCPD) and type 1 diabetes: A study from Eastern India.

BACKGROUND AND AIMS: We aimed to identify clinical characteristics and biochemical parameters at presentation in newly diagnosed children and adolescents with Fibrocalculous pancreatic diabetes (FCPD) and compare them with Type 1 Diabetes (T1D) children. METHODOLOGY: A retrospective chart review yielded 226 patients (below 18 years) who presented and fulfilled diagnostic criteria of diabetes mellitus. Classification of diabetes was based on American Diabetes Association (ADA), World Health Organization (WHO), International Society for Paediatric and Adolescent Diabetes (ISPAD), and Mohan's criteria and all patients underwent abdominal X-ray. RESULTS: A total of 31 (13.7%) patients fulfilled criteria of FCPD and 63 (27.9%) of autoantibody positive T1D. When comparing FCPD with T1D at presentation, FCPD patients were older, 14.23 years vs 11.32 years. Fewer FCPD patients presented with Diabetic Ketoacidosis (3.2% vs 34.9%), osmotic symptoms (54.8% vs 93.7%) with significantly longer median duration of symptoms (4.0 vs 1.0 months) and had more abdominal pain (58.06% vs 6.3%) & diarrhoea (38.71% vs 1.6%) as compared to patients with T1D". FCPD patients had higher c-peptide levels (median-0.85 vs 0.61) and required higher mean dose of insulin compared to T1D (1.16 U/kg vs 1.01 U/kg). At presentation fasting plasma glucose was significantly higher in T1D than FCPD, but no difference was noted in post prandial glucose and HbA1c. CONCLUSION: There is a significant difference in clinical characteristics and biochemical parameters at presentation between FCPD and T1D patients with a longer symptom duration but insidious course in the former. To the best of our knowledge, this is the first study to report suitable cut-offs for age, c-peptide, duration of symptoms and insulin dose requirement which could be helpful for differentiating FCPD from T1DM patients.

Real world study of short term efficacy, safety, and tolerability of canagliflozin 100 mg initiation in type 2 diabetes mellitus patients during hot humid Indian summer.

BACKGROUND AND AIM: To assess short term (3 months) efficacy, safety, and tolerability of canagliflozin 100 mg among type 2 diabetes mellitus (T2DM) initiated during hot humid Indian summer. METHODS: A prospective, observational, multi-center study of 300 T2DM patients with inadequate glycemic control (i.e., HbA1c of ≥6.5%) with or without other antihyperglycemic agents (AHA) were enrolled in the study in the month of March. The objective of the study was to assess the efficacy that is changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), blood pressure (BP), lipid profile, body mass index (BMI) and safety of canagliflozin with regards to genitourinary infection, fall, diabetic keto acidosis (DKA) episodes, blood ketone and beta-hydroxybutyrate levels. All patients were initiated on canagliflozin 100 mg once daily for 12 weeks, irrespective of background medications. RESULTS: At 12 weeks, a significant reduction was observed in all the glycemic parameters,BMI, BP, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, a nonsignificant reduction in estimated glomerular filtration rate (eGFR) was observed at 12 weeks. A total of 9 adverse events were reported including 2 episodes of urinary tract infection (UTI) and 4 episodes of genital infection. The blood ketone, beta-hydroxybutyrate levels were found to be within normal limits and no episode of DKA was reported at 12 weeks. None of our patients had reported any volume depletion related adverse events viz. postural hypotension, giddiness etc. CONCLUSION: Canagliflozin 100 mg can be safely initiated in type 2 diabetes patients during hot humid Indian summer, irrespective of background medications and is effective and well tolerated.

Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options.

BACKGROUND AND AIMS: Evaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up. METHODS: We collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included. RESULTS: In ninety-five patients' (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m2 respectively. CONCLUSIONS: Significant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.

Assessment of Patient, Physician, Caregiver, and Healthcare Provider-Related Factors Influencing "Glycemic Happiness" of Persons with Type 2 Diabetes Mellitus: An Observational Survey.

A multicentric cross-sectional observational survey was conducted to understand the patient, physician, nurse, caregiver, and diabetes counselor/educator-related factors that define the "glycemic happiness" of persons with type 2 diabetes mellitus (T2DM). Five sets of questionnaires based on a five-point Likert scale were used. A total of 167 persons with T2DM, 167 caregivers, and 34 each of physicians, nurses, and diabetes counselors/educators participated. For persons with T2DM, an adequate understanding of diabetes (mean score ± standard deviation: 4.2 ± 0.9), happiness and satisfaction with life (4.1 ± 0.8), flexibility (4.2 ± 0.8) and convenience (4.2 ± 0.7) of treatment, and confidence to handle hypo/hyperglycemic episodes (4.0 ± 0.9) were the factors positively associated with glycemic happiness. Caregivers' factors included information from physicians on patient care (4.5 ± 0.6), constructive conversations with persons with T2DM (4.2 ± 0.8), helping them with regular glucose monitoring (4.2 ± 0.9), and caregivers' life satisfaction (4.2 ± 0.8). Factors for physicians, nurses, and diabetes counselors/educators were belief in their ability to make a difference in the life of persons with T2DM (4.8 ± 0.4, 4.4 ± 0.5, and 4.5 ± 0.5), satisfaction from being able to help them (4.9 ± 0.3, 4.6 ± 0.5, and 4.6 ± 0.5), and professional satisfaction (4.9 ± 0.4, 4.4 ± 0.6, and 4.7 ± 0.4). Our survey identified the key factors pertaining to different stakeholders in diabetes care, which cumulatively define the glycemic happiness of persons with T2DM.

Quantifying Remission Probability in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

High Thyroid-stimulating Hormone Level in Down's Syndrome: A Mere Resetting of Hypothalamopituitary Axis in Subclinical Hypothyroidism?

OBJECTIVE: Hyperthyrotropinemia (HT) or reduced thyroid function in Down syndrome (DS) is not uncommon, causes range from glandular dysgenesis to altered hypothalamopituitary axis. In the present study, we have compared hypothyroid Indian children with and without DS (NDS), especially focusing on family history, goiter, and biochemical features. METHODS: We conducted this retrospective observational study from previous medical records of children with DS (1-17 years) having an elevated TSH (≥5 mIU/L) who were consecutively referred for with HT to Endocrinology OPD of a tertiary care hospital in India. Records from hypothyroid children (1-17 years) without Down Syndrome (NDS) were evaluated as controls. Free thyroxine (FT4), anti-thyroid peroxidase (TPO) antibody were measured and congenital hypothyroidism was excluded in all subjects. RESULTS: Thirty-four DS cases [median age 8 years (IQR: 2-14), M: F = 13:21] and 34 controls [median age 10.5 years (IQR: 7-13.25), M: F = 13:21] were comparable in terms of age and sex, Median age of presentation was significantly earlier in case of DS vs NDS [7 years vs. 10 years]. DS children had significantly less family history of thyroid disorders compared to NDS [14.7% vs 64.7%]. Goiter was significantly less common in patients with DS [DS - 32.25% vs. NDS - 73.5%, P = 0.001]. Anti-TPO antibody positivity was significantly less common in patients with DS [DS- 41% vs. NDS- 73.5%, P = 0.014]. CONCLUSION: There is a significant difference in presentation in hypothyroid children with DS compared to NDS. DS children with hypothyroidism compared to NDS, had earlier presentation, lower incidence of traceable family history, goiter, and anti-TPO-antibody positivity.

Juvenile Hypothyroidism: A Clinical Perspective from Eastern India.

INTRODUCTION: Juvenile hypothyroidism (JH) can have deleterious effects on growth, pubertal development, and scholastic performance of children. In India, there is a paucity of data on acquired hypothyroidism in children, in contrast to congenital hypothyroidism. Our objective was to assess the profile of JH in a referral clinic from eastern India. MATERIALS AND METHODS: For this study, 100 patients with documented acquired hypothyroidism (subclinical and overt) (aged <18 years), from eastern India, were evaluated retrospectively. Evaluation included history as well as clinical, biochemical, and ultrasonography parameters. RESULTS: Out of the 100 participants, 74% had overt hypothyroidism (OH), while 26% had subclinical hypothyroidism (SCH). The majority of the participants were females (66%). The mean age at detection was 8.95 ± 3.96 years in the SCH group and 8.38 ± 3.29 years in the OH group. A family history of thyroid disorder and/or goiter was present in 35% of the patients. Goiter was the most common presentation in both SCH and OH, with overall prevalence of 58%. Height below 3rd percentile was significantly higher (28%) in OH group compared to 4% in SCH group. Five percent of OH subjects were obese. Worsening school performance was reported in only 9% of subjects. Only 4% (all males) presented with delayed puberty, while one female (1%) presented with precocious puberty. Sixty-four percent of OH group were TPOAb positive compared to only 15% in SCH group. Five percent of our study population had type-1 diabetes mellitus (T1DM) and 7% had Down syndrome (DS). CONCLUSION: In our study, JH showed significantly higher female preponderance and TPOAb positivity in OH group, in comparison to SCH group. Family history of thyroid disorder and/or goiter was present in a significant proportion of patients. Goiter was the most common presentation of JH. Height deceleration, weight gain, and fatigue were the other common presentations. Prevalence of short stature was significantly higher in OH group. Interestingly, in contrast to prevalent notion, only 5% of OH were obese and worsening school performance was observed to be rare. Puberty disorders (both delayed and precocious) may occur in JH as seen here. Because of strong association, those with T1DM or DS should be screened for JH and vice versa in TIDM.

An observational prospective study to evaluate the outcomes of new onset diabetes after renal transplantation (NODAT) in a tertiary care centre in eastern India.

AIM: To analyse post-transplant outcomes of NODAT patients in comparison to the regular cohort (non-NODAT). OBJECTIVES: To compare graft survival and rejection rate, patient survival rate, incidence of hospitalization (due to any cause) in between NODAT and non-NODAT groups in cases of renal transplantation. METHODS: A single-centred prospective real-world observational study of 100 subjects who underwent renal transplantation over a period of two years. All NODAT cases evaluated for graft survival/rejection, incidence of hospitalisation/infection, mortality from all causes and compared with that of non-NODAT post-transplant recipients. Nominal categorical data between the groups are compared using Chi-square test or Fisher's exact test as appropriate. p value < 0.05 was taken to indicate a significant difference. RESULTS: Mean number of hospital admissions of subjects was 1.38 ± 1.38 and 0.29 ± 0.56 in NODAT and Non-NODAT respectively, p < 0.0001. Nineteen out of 24 NODAT subjects and 72 out of 76 Non-NODAT subjects had graft survival, p = 0.0342. Twenty out of 24 NODAT and 74 out of 76 Non-NODAT subjects had survived, p = 0.0282. CONCLUSIONS: NODAT leads to adverse outcomes viz. increased rate of hospitalization, reduced rates of allograft survival and patient survival.

Legions of Presentations of Myxedema Coma: A Case Series from a Tertiary Hospital in India.

Myxedema coma is associated with decreased mental status and hyponatremia among patients with diagnosed or undiagnosed hypothyroidism. The diagnosis is challenging in the absence of universally accepted diagnostic criteria, but should be considered as a differential even in cases with competing established diagnoses. All patients should receive intensive care level treatment. Even with optimal treatment, mortality is very high.