Emerging pattern of asymptomatic hyperparathyroidism in South India - a six-year retrospective study.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable presentation. There is a recent increase in the number of asymptomatic cases due to the use of multichannel automated analyzers.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Insulin Glargine in Type 1 Diabetes Mellitus: A Review of Clinical Trials and Real-world Evidence Across Two Decades.

BACKGROUND: Over the past two decades, insulin glargine 100 U/mL (Gla-100) has emerged as the "standard of care" basal insulin for the management of type 1 diabetes mellitus (T1DM). Both formulations, insulin glargine 100 U/mL (Gla-100) and glargine 300 U/mL (Gla- 300) have been extensively studied against various comparator basal insulins across various clinical and real-world studies. In this comprehensive article, we reviewed the evidence on both insulin glargine formulations in T1DM across clinical trials and real-world studies. METHODS: Evidence in T1DM for Gla-100 and Gla-300 since their approvals in 2000 and 2015, respectively, were reviewed. RESULTS: Gla-100 when compared to the second-generation basal insulins, Gla-300 and IDeg-100, demonstrated a comparable risk of overall hypoglycemia, but the risk of nocturnal hypoglycemia was higher with Gla-100. Additional benefits of Gla-300 over Gla-100 include a prolonged (>24- hours) duration of action, a more stable glucose-lowering profile, improved treatment satisfaction, and greater flexibility in the dose administration timing. CONCLUSION: Both glargine formulations are largely comparable to other basal insulins in terms of glucose-lowering properties in T1DM. Further, risk of hypoglycemia is lower with Gla-100 than Neutral Protamine Hagedorn but comparable to insulin detemir.

A Comparison of Lower Doses of Porcine Sequence Corticotropin with Standard Dose in Testing the Hypothalamic Pituitary Adrenal Axis in Healthy Individuals.

Context: Porcine sequence corticotropin (PSC) stimulation test (PSCST) is a reliable, cost-effective alternative to the short Synacthen test. Long-acting PSC is widely available as a 300 IU multidose vial (60 IU per 1 ml). Aims: To compare the efficacy of lower doses of PSC that can be given directly from the multidose vial without reconstitution, with standard dose in assessing the hypothalamic pituitary adrenal (HPA) axis in healthy individuals. Settings and Design: Prospective study comparing different doses of PSC. Methods and Material: In 13 healthy volunteers, serum Cortisol was estimated at 30 and 60 minutes after intramuscular administration of 24IU/250 µg standard dose (0.4 ml) and lower doses of PSC (18 IU/0.3 ml/;12 IU/0.2 ml; and 6 IU/0.1 ml), with a gap of 4 weeks between each dose. Statistical Analysis Used: Mean ± SD was used to express quantitative variables. ANOVA and paired T-test were used for statistical analysis. Results: The mean ± SD of peak Cortisol levels after PSCST with all doses of PSC were >18 ug/dl. The means of peak Cortisol responses to different doses of PSC among subjects were comparable. In a subject, there was no significant dose effect and interaction (dose x time) effect indicating that the different doses were comparable (both at 30 and 60 minutes) (p = 0.735). Conclusions: All tested lower doses of PSC obtained from the multidose vial without reconstitution, including the lowest dose (6 IU/62.5 µg) tested, were comparable in efficacy to the standard dose (24IU/250 µg) in assessing the adequacy of HPA axis in healthy individuals.

A Review on Vitamin D Deficiency and Related Disorders: What is the Right Serum Vitamin D Level?

To maintain a healthy skeleton, vitamin D is crucial for phosphate as well as calcium uptake. It is of great significance for maintaining the various adaptive and innate immune response components. To reduce the development of various immune-related disorders, such as diabetes, hypertension, cardiovascular diseases, rheumatoid arthritis, and coronavirus disease 2019 (COVID-19), numerous studies evaluating the optimal threshold levels for serum 25-hydroxyvitamin D [25(OH)D]. It is documented in various evidence to increase the serum 25(OH)D intake from the current mindset of 30-50 ng/mL to attain the best overall vitamin D benefits. These values are in line with the results of various research showing that increased vitamin D intake is linked to a decreased risk of cancer and cardiovascular diseases. Therefore, it becomes vital to understand the "right" vitamin D levels to avoid deficiency along with its related disorders. In contrast to 30 ng/mL, this review emphasizes the significance of increasing vitamin D levels to 50 ng/mL to obtain several physiological benefits. An individual needs at least 60000 IU for 12 weeks to maintain serum vitamin D levels above 30 ng/mL. The article will interest physicians who desire to profit fully from vitamin D's influence on clinical practice.

Expert Opinion on the Diagnosis and Management of Male Hypogonadism in India.

Male hypogonadism (MH) is a clinical and biochemical syndrome caused by inadequate synthesis of testosterone. Untreated MH can result in long-term effects, including metabolic, musculoskeletal, mood-related, and reproductive dysfunction. Among Indian men above 40 years of age, the prevalence of MH is 20%-29%. Among men with type 2 diabetes mellitus, 20.7% are found to have hypogonadism. However, due to suboptimal patient-physician communication, MH remains heavily underdiagnosed. For patients with confirmed hypogonadism (either primary or secondary testicular failure), testosterone replacement therapy (TRT) is recommended. Although various formulations exist, optimal TRT remains a considerable challenge as patients often need individually tailored therapeutic strategies. Other challenges include the absence of standardized guidelines on MH for the Indian population, inadequate physician education on MH diagnosis and referral to endocrinologists, and a lack of patient awareness of the long-term effects of MH in relation to comorbidities. Five nationwide advisory board meetings were convened to garner expert opinions on diagnosis, investigations, and available treatment options for MH, as well as the need for a person-centered approach. Experts' opinions have been formulated into a consensus document with the aim of improving the screening, diagnosis, and therapy of men living with hypogonadism.

Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential concept to assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

Use of Second-Generation Basal Insulin Gla-300 in Special Populations: A Narrative Mini-Review.

BACKGROUND AND AIMS: Hypoglycemia and insulin-related adverse events are crucial barriers to effective diabetes management, particularly in the elderly, people with renal impairment, people with diabetes fasting during Ramadan, or people with type 1 diabetes mellitus (T1DM). There is a scarcity of clinical and real-world evidence assessing the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in these special populations. To understand the entirety of evidence, this mini-review elaborates on the use of Gla-300 in diabetes management among special populations. METHODS: Clinical and real-world evidence related to the use of Gla-300 among special populations with diabetes were retrieved using PUBMED and Google Scholar. RESULTS: Gla-300 has shown improved glycemic control with stable insulin action and low risk of hypoglycemia in diverse groups with diabetes. It also appears to have an acceptable safety profile during Ramadan fasting. However, adequate monitoring and adjustment of insulin dose on an individual basis should be considered. CONCLUSION: Gla-300 is a second-generation basal insulin with proven benefits of reduced risk of hypoglycemia and improved glycemic control in special populations of people with diabetes.

Addendum 1: Forum for Injection Technique and Therapy Expert Recommendations, India.

With the emerging complexities in chronic diseases and people's lifestyles, healthcare professionals (HCPs) need to update their methods to manage and educate patients with chronic lifestyle disorders, particularly diabetes. The insulin injection technique (IIT), along with various parameters, must also be updated with newer methods. Forum for Injection Technique and Therapy Expert Recommendations (FITTER), India, has updated its recommendations to cover newer ways of detecting hypoglycaemia and lipohypertrophy, preventing needlestick injuries (NSIs), discouraging the reuse of insulin needles and encouraging good disposal. FITTER, India, is also introducing recommendations to calculate insulin bolus dose. These updated recommendations will help HCPs better manage patients with diabetes and achieve improved outcomes.

SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Clinical Utility of a Digital Therapeutic Intervention in Indian Patients With Type 2 Diabetes Mellitus: 12-Week Prospective Single-Arm Intervention Study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) having elevated levels of blood glucose and glycated hemoglobin (HbA1c) are at higher risk of macro- and microvascular complications. Nonetheless, the goal of achieving glycemic control cannot be met with the use of pharmacotherapy alone. The recent emergence of digital therapeutic tools has shown the possibility of improving the modifiable risk factors and self-management of diabetes. OBJECTIVE: The aim of this study was to examine the clinical utility of a digital therapeutic intervention as an add-on therapy to achieve glycemic control in patients with T2DM. METHODS: This was a 12-week prospective, single-arm digital intervention study in patients with T2DM receiving regular antidiabetic treatment. The eligibility criteria included male and female patients with HbA1c≥6.5%, functional English literacy, and a mobile phone capable of running the intervention app. Outcome measures of the study were mean changes in HbA1c, fasting blood glucose (FBG), postprandial blood glucose (PPBG), BMI, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index at the end of 12 weeks. RESULTS: A total of 128 participants completed the study period of 12 weeks. There were 54.7% (70/128) men and 45.3% (58/128) women with a mean age of 48.48 years (SD 10.27). At the end of 12 weeks, the mean change in HbA1c, FBG, PPBG, and BMI for the overall study population was -0.84% (P<.001), -8.39 mg/dl (P=.02), -14.97 mg/dl (P<.001), and -0.24 kg/m2 (P=.06), respectively. Among the participants showing improvement in the HbA1c value at the end of 12 weeks (responders), the mean change in HbA1c, FBG, PPBG, and BMI was -1.24% (P<.001), -12.42 mg/dl (P=.003), -21.45 mg/dl (P<.001), and -0.34 kg/m2 (P=.007), respectively. There was an increase in HOMA-IR values for the overall study population (0.54, P=.29). HbA1c response showed a significant association with a baseline HbA1c level ≥7.5%, no prior history of smoking, and no prior COVID-19 infection, as well as with higher levels of program engagement. CONCLUSIONS: A digital therapeutic intervention when used alongside standard medications significantly reduces HbA1c, FBG, and PPBG levels in patients with T2DM.

Subclinical Kwashiorkor in Adults: A New Age Paradigm.

Childhood protein-energy undernutrition (PEU) is a well-recognized problem and therefore a lot of work has been done to identify and manage paediatric PEU. Though there have been several reports of low protein consumption in adults from developing countries, PEU and its subtle forms (subclinical PEU) are not yet recognized as adult disorders. Physicians and public perception do not favour easy recognition and action. In this review, the authors provide a scoping review of the existing literature on this entity providing insights into its recognition, pathogenesis and management. Adult subclinical PEU is an enormous under-recognized challenge that can have detrimental consequences if not recognized and corrected in time. PEU has grave health and economic impact on the patient and society. Therefore, it is important to recognize subclinical PEU and prevent its progression to full-blown form.

Circulating C-Terminal Agrin Fragment: A Potential Marker for Sarcopenia Among Type 2 Diabetes.

Background: Undetected onset of sarcopenia among individuals with chronic diseases especially Type 2 Diabetes Mellitus (T2D) makes it important to be evaluated. The feasibility of diagnosing sarcopenia in a clinical setup might be a difficult task. Circulating markers including C-terminal agrin fragment (CAF) are emerging as an alternative. Hence, the objectives of the study were to compare circulating CAF levels between T2D, prediabetes (PD) and healthy controls and to study its association with sarcopenic index, muscle mass, strength and quality. Methods: Ninety-nine participants (n = 42, T2D; n = 33, PD; n = 24, healthy controls) aged 18 to 60 yrs were recruited. HOMA (homeostatic model assessment) indices were derived using plasma glucose and insulin. All participants underwent lipid profiling, muscle strength including quality (isokinetic dynamometer), body composition (Dual energy X-ray Absorptiometry (DXA)) and sarcopenic index (appendicular skeletal muscle mass/body weight) assessment. Serum samples were used to estimate CAF levelsusing enzyme-linked immunosorbent assay (ELISA). Results: Median CAF level was significantly higher among T2D group compared to PD and control groups (P < 0.0001). Circulating CAF levels correlated positively with age and glycated haemoglobin (HbA1c) (both, P < 0.001) and negatively with HOMA-B and muscle quality (both, P < 0.001), and sarcopenic index (P = 0.07). Multivariable analysis demonstrated that the odds of being in the highest tertile category was 7.67, 95% C.I. (2.10, 29.3) among T2D. Conclusion: Circulating CAF levels were significantly higher among T2D compared to PD and control study groups along with reduced skeletal muscle quality. This suggests that the circulating CAF level has the potential to be considered as a clinical marker to evaluate sarcopenia among T2D.

Incorporating Integrated Personalised Diabetes Management (iPDM) in Treatment Strategy: A Pragmatic Approach.

Diabetes is a global public health concern. Vigilant monitoring and effective management of glycaemic variations are essential to prevent complications of diabetes. Effectively incorporating monitoring strategies in management of diabetes is a serious challenge. Patient-centered approach is necessary to customise monitoring and therapy of diabetes. This has been made possible by integrating technology with personalised therapeutic strategy. The integrated personalised diabetes management (iPDM) is a holistic, patient-centered approach that focuses on personalising diabetes management to streamline therapy and improve outcome. iPDM helps strengthen the care process, facilitates communication between patients and their healthcare team, and integrates digital tools that visualise and analyse data. The five E's which includes enthusiasm, education, expertise, empathy and engagement are the key pillars of a strong foundation for the iPDM model. iPDM model is a convenient and easily accessible tool that shifts the management paradigm from an "algorithmic" to "personalized" care to optimise treatment outcomes. Structured self-monitoring of blood glucose (SMBG) should be available as part of the self-management process for people with sub-optimally controlled type 2 diabetes, including those not on insulin therapies. Different SMBG regimens should be followed based on factors such as diabetes type, treatment approach (diet, oral antidiabetic medication, or insulin), glycaemic control, available resources, and patient's level of education.

The role of oral semaglutide in managing type 2 diabetes in Indian clinical settings: Addressing the unmet needs.

AIMS: Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population. METHODS: We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation. RESULTS: Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population. CONCLUSIONS: Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents.

46 XY disorder of sex development (DSD) due to 5 alpha (SRD5A2) deficiency - Experience from a multidisciplinary Pediatric Gender Clinic.

BACKGROUND: SRD5A2 deficiency leads to incomplete masculinization of individuals with a 46 XY karyotype. A definitive diagnosis in early infancy facilitates decisions concerning choice of sex of rearing and management. AIM: To review the clinical presentation, diagnosis, treatment and outcome of children with 46 XY DSD due to SRD5A2 deficiency at a Paediatric Gender Clinic. STUDY DESIGN AND METHODS: Retrospective review of cases of SRD5A2 deficiency (2000-15) managed with a standard protocol at a multidisciplinary clinic. Demographic data, clinical presentation, physical findings, investigations (hormonal profile, imaging, genitoscopy), psychological evaluation (child, family), medical and surgical management, outcome and follow up were collated and analyzed. RESULTS: There were 12 cases aged 3 days-14 years at presentation, 3 had parental consanguinity. Eight were reared as males and 4 as females. Specialist referral was sought for hypospadias (5), atypical genitalia (5) or incongruent pubertal masculinization (2). All had chordee, symmetrical inguinoscrotal gonads, rugose labioscrotum and proximal hypospadias (perineoscrotal -9, perineal -3). Both pubertal cases had significant masculinization and no gynecomastia. The median testosterone/dihydrotestosterone ratio was 22.1(IQR-8.6-55.7). Despite a classical phenotype, four (2 prepubertal, 2 pubertal) had a ratio <10. Genitoscopy showed urogenital sinus remnant (4) and hypoplastic verumontanum (5). Sex reassignment was done in 4. Surgical management was staged and completed by 4 years in those with infantile presentation. Besides correction of chordee and urethroplasty in 11, other procedures included orchidopexy (5), excision of a urogenital sinus remnant (4) and correction of penoscrotal transposition (4). The urethroplasty was single staged in 3. All operated cases were followed up (mean age at last follow up - 10.63 years, mean follow up period - 7.25 years). The overall cosmetic result was satisfactory, but the phallic structure remained relatively small across prepubertal period. Uroflowmetry curves were normal in 9. All showed penile tumescence/erection and two peripubertal cases had typical secondary sexual characters. All cases, including those with sex reassignment, have a well-adjusted male psyche. DISCUSSION AND CONCLUSION: The diagnosis, management and longitudinal follow up of cases of SRD5A2 deficiency at a multidisciplinary gender clinic is presented. Diagnostic dilemmas with low T/DHT ratios remained in a third of cases. Most were diagnosed in infancy and assigned a male sex of rearing, all underwent staged masculinizing genitoplasty. Those with sex reassignment also fared well with comprehensive management after family counseling.

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.

SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.