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.

Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

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.

Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity?

BACKGROUND & OBJECTIVES: Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India. METHODS: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T3, T4, TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium. RESULTS: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P = 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 µg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 µg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group (P < 0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 µg/l) as compared to controls (11, 6.4%; P < 0.001). Serum ferritin level negatively correlated with the presence of goitre (r = -0.22, P = 0.008) and had an OR of 2.8 (CI 1.20-6.37, P = 0.017). INTERPRETATION & CONCLUSIONS: There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.

Insulinization in T2DM with Basal Analogues During COVID-19 Pandemic: Expert Opinion from an Indian Panel.

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

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.

Effectiveness of Amlodipine on Blood Pressure Control in Hypertensive Patients in India: A Real-World, Retrospective Study from Electronic Medical Records.

BACKGROUND: The effectiveness of amlodipine has been reported in clinical trials in India. However, real-world data on the effectiveness of amlodipine in India is limited. OBJECTIVE: To provide real-world evidence regarding the effectiveness of amlodipine as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥ 140/90 mmHg) and were prescribed amlodipine as monotherapy or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of amlodipine. Change in systolic (SBP) and diastolic (DBP) blood pressure from baseline was the primary endpoint. Evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines was the secondary endpoint. Readings were obtained before initiating amlodipine and after at least a month of therapy with amlodipine. RESULTS: Among the 462 included patients, the majority (90.7%) were on amlodipine monotherapy or amlodipine + 1AHD. Mean (95% confidence interval [CI]) change in the amlodipine monotherapy group was: SBP (- 12.1 [- 14.9, - 9.3] mmHg) and DBP (- 7.5 [- 8.9, - 6.1] mmHg) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 17.8 [- 21.0, - 14.6] mmHg) and DBP (- 9.5 [- 11.0, - 8.0] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 31.4% and 42.9% of patients on amlodipine monotherapy and by 38.9% and 51.8% of patients on amlodipine + 1AHD, respectively. Among patients aged ≤ 45 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 11.7 [- 16.0, - 7.4] mmHg; P < 0.001) and DBP (- 7.2 [- 9.7, - 4.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 14.6 [- 21.9, - 7.3] mmHg; P < 0.05) and DBP (- 10.6 [- 14.8, - 6.4] mmHg; P < 0.01). SBP and DBP goals were achieved by 35.4% and 33.8% of patients on amlodipine monotherapy and by 48.0% and 56.0% of patients on amlodipine + 1AHD, respectively. Among patients aged ≥ 65 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 13.9 [- 20.2, - 7.6] mmHg; P < 0.01) and DBP (- 8.5 [- 11.4, - 5.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 22.4 [- - 28.8, - 16.0] mmHg; P < 0.001) and DBP (- 10.8 [- 14.0, - 7.6] mmHg; P < 0.001). SBP and DBP goals were achieved by 25.5% and 13.7% of patients on amlodipine monotherapy and by 29.8% and 14.0% of patients on amlodipine + 1AHD. CONCLUSION: Amlodipine prescribed as monotherapy or add-on therapy during routine clinical practice significantly reduced BP in ≤ 45- and ≥ 65-year-old Indian patients with mild to moderate hypertension, emphasizing that amlodipine may be a good candidate for BP control in Indian patients with essential hypertension in these age groups.

Effect of Gliclazide or Gliclazide plus Metformin Combination on Glycemic Control in Patients with T2DM in India: A Real-World, Retrospective, Longitudinal, Observational Study from Electronic Medical Records.

BACKGROUND: The efficacy of gliclazide has been reported in clinical trials in India. However, real-world data on the effectiveness of gliclazide in India is unavailable. OBJECTIVE: To provide real-world evidence regarding the effectiveness of gliclazide or gliclazide + metformin fixed-dose combination or separate medications, used either as monotherapy or as the latest add-on to other antihyperglycemic agents in reducing glycated hemoglobin (HbA1c) levels in Indian patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic medical record data of adult patients who were diagnosed with T2DM who were newly initiated on or had been prescribed gliclazide or gliclazide + metformin combination for < 30 days as monotherapy or as add-on therapy to other antihyperglycemic agents, and had HbA1c ≥ 6.5% were retrospectively analyzed. Mean change in HbA1c from baseline was the primary endpoint. Secondary endpoints were assessment of dosages and formulations of gliclazide or gliclazide + metformin prescribed in the HbA1c spectrum and antihyperglycemic agents to which gliclazide or gliclazide + metformin was added as an adjunct. Readings were obtained before initiating gliclazide or gliclazide + metformin and after at least 90 days of treatment with gliclazide or gliclazide + metformin. RESULTS: Included patients (n = 498) were categorized into gliclazide only (n = 66), gliclazide + metformin only (n = 179), gliclazide add-on (n = 169), and gliclazide + metformin add-on (n = 84) groups. Mean (95% confidence interval [CI]) change in HbA1c among patients with baseline HbA1c > 7% was - 0.8% (- 1.26, - 0.34) in gliclazide only group; - 1.6% (- 1.89, - 1.31; p < 0.001) in gliclazide + metformin group; - 1.2% (- 1.50, - 0.90; p < 0.001) in add-on gliclazide group; and - 1.4% (- 1.75, - 1.05; p < 0.001) in add-on gliclazide + metformin group. Gliclazide once daily was the most prescribed regimen in the gliclazide only group (72.7%), with 60 mg being the most prescribed modified-release dose (62.5%). Gliclazide + metformin twice daily was the most prescribed regimen in the gliclazide + metformin group (69.3%) with 80 mg + 500 mg being the most prescribed immediate-release dose (62.9%). Gliclazide and gliclazide + metformin were most added as an adjunct to existing prescriptions of biguanides (83.4%) or insulin (64.3%), respectively. CONCLUSION: Gliclazide or gliclazide + metformin prescribed as mono- or add-on therapy during routine clinical practice effectively reduced HbA1c in Indian patients with T2DM, thus validating the use of gliclazide and gliclazide + metformin for managing T2DM in India.

Vitamin D status and its seasonal variability in healthy young adults in an Asian Indian urban population.

OBJECTIVE: To assess the vitamin D status and its seasonal variability in healthy young adults in Chandigarh, a city in northern India. METHODS: The history was elicited and examination was performed pertaining to metabolic bone disease in 329 young adults (18 to 25 years of age) at the end of summer and 237 subjects from the same cohort at the end of winter. The calcium profile, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone were measured during both the seasons. RESULTS: Among the young adults in this study cohort, 25(OH)D sufficiency (≥ 30 ng/mL) was found in 72.5% in summer and in 50.7% in winter. A significantly higher number of men were 25(OH)D sufficient in comparison with women in summer (P = .001). The mean (standard deviation) serum 25(OH)D levels were significantly higher at the end of summer-52.9 (33.7) ng/mL-in comparison with that at the end of winter-31.8 (21.1) ng/mL; P<.001. The intact parathyroid hormone levels were significantly lower in the 25(OH)D-sufficient group (P = .001) and began to increase at 25(OH)D levels below 25 ng/mL. The serum 25(OH)D levels correlated positively with the duration of exposure to sunlight during summer (r = 0.111; P = .05) and also the calcium intake during summer (r = 0.129; P = .03). CONCLUSION: Vitamin D sufficiency may be a reality with a combination of young skin, optimal and effective exposure to sunlight, and adequate calcium intake.

Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus.

Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.