Differences in the Presentation and Outcome between Premenopausal and Postmenopausal Primary Hyperparathyroidism Indian Women: A Single-Center Experience.

Introduction: Primary hyperparathyroidism (PHPT) is an endocrine disorder wherein enlargement of one or more of the parathyroid glands causes autonomous overproduction of the parathyroid hormone (PTH), which leads to high serum calcium levels. Objective: The objective of this study was to compare the clinical, laboratory, and operative variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT. Materials and Methods: A retrospective analysis of the data of female patients who underwent surgery for PHPT at a single center, from January 2011 to December 2020, was done. Patients with familial PHPT and secondary hyperparathyroidism were not included. Results: Of the 130 women with PHPT, 44.6% were pre-M and 55.4% were post-M. A significantly higher number of pre-M females were symptomatic compared to post-M females (pre-M vs. post-M, 84.5% vs. 68.1%, P = 0.031). Renal calculi were more common in pre-M women (34.5% vs. 18.1%, P = 0.032), while the rest of the clinical features were comparable between the two groups. The proportion of women with osteoporosis (6.7% vs. 19.4%, P = 0.071), hypertension (13.8% vs. 34.7%, P = 0.012), and diabetes mellitus (3.5% vs. 16.7%, P = 0.033) was lesser in the pre-M group. Elevated serum alkaline phosphatase levels were significantly more prevalent in the pre-M group (37.9% vs. 20.8%, P = 0.032). The mean serum calcium (12.35 ± 1.28 vs. 11.96 ± 1.22 mg/dL, P = 0.079), median serum PTH (334 vs. 239 pg/mL, P = 0.051), and median weight of the operated adenomas (1.75 vs. 1.45 g, P = 0.075) were also higher in pre-M females. The proportion of ectopic adenomas and multiple adenomas, presurgery adenoma localization rates, and disease cure rates did not differ according to the menopausal status. The occurrence of postoperative hungry bone syndrome was higher in the pre-M women (15.5% vs. 1.4%, P = 0.008). Conclusion: The majority of women with PHPT are post-M, but symptomatic presentation is more common in pre-M females. The severity of the disease appears to be more in pre-M women; however, imaging and operative variables generally did not significantly differ between the two groups.

LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries.

INTRODUCTION: Real-world evidence on insulin glargine 100 U/ml (Gla-100) initiation in Indian type 2 diabetes mellitus (T2DM) individuals is limited. The present study aimed to evaluate the effectiveness of Gla-100 in insulin-naïve T2DM participants from India. METHODS: This post hoc analysis includes real-world data of insulin-naïve Indian participants with T2DM who started Gla-100 treatment in two Asian registries: FINE ASIA and GOAL. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, insulin dose, and incidence of hypoglycemia from baseline to 6 months were assessed. RESULTS: A total of 955 participants with T2DM were identified and analyzed. The mean [standard deviation (SD)] age and duration of diabetes were 54.7 (9.8) years and 9.8 (6.3) years, respectively. Mean HbA1c and FPG were significantly reduced after 6 months of Gla-100 treatment [- 2.07 (1.4) %; - 94.4 (65.2) mg/dl, respectively]. HbA1c targets of < 7.0% and < 7.5% were achieved by 292 (30.6%) and 589 (61.7%) study participants, respectively. The overall incidence of hypoglycemia was low (n = 52; 5.4%); only two participants (0.2%) reported severe hypoglycemia. Insulin was titrated with a mean (SD) increment of 2.5 (5.6) U/day after 6 months, leading to a mean Gla-100 dose of 18.2 (8.9) U/day. Mean body weight remained unchanged from baseline to 6 months (- 0.1 kg). CONCLUSION: In routine clinical practice, Gla-100 significantly improved glycemic parameters after 6 months of treatment with a low risk of hypoglycemia and no weight change in participants with T2DM.

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.

Differences in the Clinical Presentation and Biochemical Profile of the Patients with Primary Hyperparathyroidism with regard to their Serum Vitamin D Levels: a Single-center Experience.

The association between vitamin D deficiency and primary hyperparathyroidism (PHPT) is common and has clear implications. Vitamin D deficiency is commonly seen in PHPT population and exacerbates its severity with skeletal and metabolic effects. Retrospective data collection and review were done in patients who underwent surgery for PHPT at a tertiary care hospital in India between January 2011 and December 2020. A total of 150 subjects were included in the study and were divided into group 1 (vitamin D < 20 ng/ml, deficient), group 2 (vitamin D 21-29 ng/ml, insufficient), and group 3 (vitamin D > 30 ng/ml, sufficient). There was no difference in the duration of symptoms or the symptomatology between the three groups. Mean pre-operative serum calcium and serum phosphorous levels were also comparable in all the three groups. Mean pre-operative parathyroid hormone (PTH) levels in the three groups were 703 ± 996 vs 343.6 ± 396 vs 343.6 ± 396 pg/ml, respectively (P = 0.009). There was a statistically significant difference in group 1 vs groups 2 and 3 in their mean weight of the parathyroid gland (P = 0.018) and high alkaline phosphatase (ALP) levels (P = 0.047). Post-operative symptomatic hypocalcemia was observed in 17.3% of patients. Post-operative hungry bone syndrome occurred in 4 patients, all in group 1. PHPT in patients with low serum vitamin D was associated with higher serum PTH levels, increased frequency of high serum ALP levels, and higher weight of the excised gland, with no difference in the serum calcium and phosphorous.

Evolution of Guideline Recommendations on Insulin Therapy in Type 2 Diabetes Mellitus Over the Last Two Decades: A Narrative Review.

The prevalence of type 2 diabetes mellitus has been increasing worldwide. As the therapeutic options for type 2 diabetes mellitus have evolved over the last 2 decades, national and global guidelines related to type 2 diabetes mellitus pharmacotherapy issued by various organizations have tended to vary in their recommendations. This narrative review aimed to analyze the key recommendations by major global and national guidelines on the initiation of insulin therapy in patients with type 2 diabetes mellitus over the last 20 years. Strategies for insulin therapy for titration and intensification were also assessed. All guidelines recommend initiation of insulin (basal/ premixed/other formulations) when glycemic targets are not achieved despite lifestyle measures and oral antidiabetic drugs. In the recent decade, early initiation of insulin has been recommended when the glycated hemoglobin levels are >10% or blood glucose levels are ≥300 mg/dL (16.7 mmol/L). Initiation is recommended at a dose of 10 units or 0.1-0.2 U/kg. Titration is advised to achieve the optimal dosage, while intensification is recommended when glycemic targets are not achieved despite titrating to an acceptable level. Glucose monitoring at periodic intervals is recommended for adequate glycemic control. The guidelines further suggest that the choice of insulin should be individualized, considering the clinical status of patients with type 2 diabetes mellitus. The physicians as well as patients should be a part of the decisions made regarding the therapeutic choice of regimen, preparation, and delivery device.

Role of Telemedicine in Diabetes Management.

INTRODUCTION: Telemedicine is a growing arena that may increase access to care for patients with diabetes. It has more relevance for rural populations or those with limited physical access to health care, for improving diabetes care. Telemedicine can also be used to offer diabetes self-education and transportation barriers for patients living in under-resourced areas or with disabilities. METHOD: "This review explores the landscape of telemedicine approaches and evidence for incorporation into general practice. RESULTS & DISCUSSION: Telehealth platforms have been shown to be both feasible and effective for health care delivery in diabetes, although there are many caveats that require tailoring to the institution, clinician, and patient population. Research in diabetes telehealth should focus next on how to increase access to patients who are known to be marginalized from traditional models of health care.

Fracture Liaison Services in India: Challenges and Opportunities.

Osteoporosis, often referred to as the "silent thief of bones," is defined by the National Institutes of Health as the "skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk for fracture."1 Fragility fractures, which result from minor or unnoticed trauma, are more than just physical injuries; they have far-reaching consequences that not only lead to severe pain and reduced mobility but also affect aspects like quality of life, healthcare costs, and overall societal well-being. Literature shows that in postmenopausal women after hip fractures, the expected survival decreases from 12 to 20%.2.

Role and Significance of Dietary Protein in the Management of Type 2 Diabetes and Its Complications in India: An Expert Opinion.

BACKGROUND: Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. AIM: An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. METHODOLOGY: A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. RESULTS: There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. CONCLUSION: Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.

Prevalence of Bacterial Urinary Tract Infection Among Patients With Type 2 Diabetes Mellitus on Sodium-Glucose Cotransporter-2 Inhibitors: A Prospective Real-World Setting Study.

Background: Genitourinary tract infections, mycotic as well as bacterial, as defined by clinical symptoms, are one of the common adverse effects associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients in clinical trials. However, Indian data in terms of the prevalence of culture-proven bacterial type of urinary tract infection (UTI), and the causative organism is limited. Objective: This study aimed to determine the prevalence and causative agents of bacterial UTI among patients with T2DM on SGLT2i. Methodology: This was a prospective longitudinal study involving all patients with T2DM who were prescribed with SGLT2i, uncontrolled on other oral anti-diabetic medications, from June 2019 to February 2020. Prevalence of bacterial UTI was evaluated at baseline and 12 weeks after initiation of SGLT2i. Results: A total of 80 patients were started on SGLT2i. One female patient on canagliflozin had significant asymptomatic bacteriuria and the causative agent was Acinetobacter baumannii. One male patient on dapagliflozin had symptomatic UTI with negative urine culture study. Four patients developed genital mycotic infection. Conclusion: In this real-world study, SGLT2i as a class, was well tolerated with favorable safety profile, and risk of developing significant bacteriuria and/or symptomatic UTI was minimal.

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting.

The Asian-Indian phenotype of type 2 diabetes mellitus is uniquely characterized for cardio-metabolic risk. In the context of implementing patient-centric holistic cardio-metabolic risk management as a priority, the choice of various combinations of antidiabetic agents should be individualized. Combined therapy with two classes of antidiabetic agents, namely, dipeptidyl peptidase 4 inhibitors and sodium-glucose co-transporter-2 inhibitors, target several pathophysiological pathways. The wide-ranging clinical outcomes associated with this combination, including improvement of glycemia and adiposity, reduction of metabolic and vascular risk, safety, and simplicity for sustainable compliance, are extremely relevant to the Asian Indian patient population living with T2DM. In this review we describe the available evidence in detail and present a rational practical guidance for the optimum clinical use of this combination in this patient population.

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.

The Indian Society for Bone and Mineral Research (ISBMR) position statement for the diagnosis and treatment of osteoporosis in adults.

The Indian Society for Bone and Mineral Research (ISBMR) has herein drafted clinical practice guidelines for the diagnosis and management of osteoporosis for the people of India. Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India. PURPOSE: In India, osteoporosis is a major public health problem. However, in the absence of any robust regional guidelines, the screening, treatment, and follow-up of patients with osteoporosis are lagging behind in the country. METHODS: The Indian Society for Bone and Mineral Research (ISBMR), which is a multidisciplinary group of physicians, researchers, dietitians, and epidemiologists and who study bone and related tissues, in their annual meeting, drafted the guidelines for the diagnosis and management of osteoporosis that would be appropriate in a resource constraint setting like India. RESULTS: Diagnosis of osteoporosis can be made in a patient with minimal trauma fracture without the aid of any other diagnostic tools. In others, bone mineral density measured by dual-energy X-ray absorptiometry remains the modality of choice. Data indicates that osteoporotic fractures occur at an earlier age in Indians than in the West; hence, screening for osteoporosis should begin at an earlier age. FRAX can be used for fracture risk estimation; however, it may underestimate the risk of future fractures in our population and still needs validation. Maintaining optimum serum 25-hydroxyvitamin D levels is essential, which, in most cases, would require regular vitamin D supplementation. Pharmacotherapy should be guided by the presence/absence of vertebral/hip fractures or the severity of risk based on clinical factors, although bisphosphonates remain the first choice in most cases. Regular follow-up is essential to ensure adherence and response to therapy. CONCLUSIONS: Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India.

Demographic and clinical profile of youth onset diabetes patients in India-Results from the baseline data of a clinic based registry of people with diabetes in India with young age at onset-[YDR-02].

BACKGROUND: We here report the demographic and clinical profile of the patients enrolled in the Indian Council of Medical Research funded Registry of people with diabetes in India with young age at onset (YDR) from 1 January 2000 to 31 July 2011. METHODS: The YDR registry recruits all diabetes cases (newly diagnosed or treated) reporting on or after 1 January 2000 with age of diagnosis ≤25 years, and residing within the assigned geographical area of the reporting centres. A baseline proforma was used to obtain information on demographic and clinical details at registration. RESULTS: The registry has enrolled 5546 patients (49.5% male; 50.5% female) with youth onset diabetes from 205 reporting centres linked to 8 regional collaborating centres (RCC) across India. T1DM (63.9%; n = 3545) and T2DM (25.3%; n = 1401) were the commonest variants of youth onset diabetes, though their relative proportion varied across RCCs. The mean (SD) age at diagnosis for T1DM was 12.9 (6.5) years, while that for T2DM was 21.7 (3.7) years. Nearly half the T1DM patients were registered within 6 months of the onset of disease. Most cases of T2DM (47.3%) were registered after 3 years from their date of diagnosis. 56.1% of patients had at least one episode of hospitalization at registration. CONCLUSION: The observations from YDR registry indicate the need to establish a surveillance system in India to monitor diabetes in youth, not only to understand its complex etiology and natural history but also due to its detrimental socio economic impact.

Lilly Insulin Glargine Versus Lantus® in Type 2 Diabetes Mellitus Patients: India and East Asia Subpopulation Analyses of the ELEMENT 5 Study.

BACKGROUND AND OBJECTIVES: Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations. METHODS: Patients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24. RESULTS: Within-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002). CONCLUSION: Efficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population. CLINICAL TRIAL REGISTRATION: NCT02302716.

Tumor-induced osteomalacia: experience from three tertiary care centers in India.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or 'inappropriately normal' FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group.

Clonidine Stimulation Test: Is Single Best Time Point, Convenient Yet Efficacious?

CONTEXT: To find a single time point during clonidine stimulation test (CST), with highest diagnostic value to rule out growth hormone deficiency (GHD). SETTINGS AND DESIGN: This is a retrospective study of 79 CSTs carried out in a tertiary care center in India. MATERIALS AND METHODS: A cohort of 79 children with unexplained short stature was divided into two groups: GHD and non-GHD. Any one stimulated growth hormone (GH) level >10 ng/mL was used to rule out GHD. Diagnostic accuracy of not only single time points but also time points in pairs was calculated. STATISTICAL ANALYSIS: The data were analyzed using SPSS statistical software 22.0. Descriptive statistics were used for analyzing demographic data. Mode for time to peak GH was calculated in each group. The specificity and false positive rates at each time point as well as combined time points were determined. RESULTS: Assaying a single sample at 60 min after clonidine resulted in 20.5% false positive tests with specificity of 79.5%. Addition of the 90 min sample increased specificity to 92.3%. CONCLUSION: The 60 min sample after clonidine stimulation was the best single sample to rule out GH deficiency. Combined sampling at 60 min + 90 min is economical and less cumbersome, with minimal compromise on the specificity.