An overview of therapeutic options of obesity management in India: the Integrated Diabetes and Endocrinology Academy (IDEA) 2023 Congress update.

INTRODUCTION: With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India. AREAS COVERED: After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity. EXPERT OPINION: Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Curious Case of a Giant Retroperitoneal Cyst.

Adrenal cysts are uncommon fluid-filled masses that develop in the adrenal gland. Typically, they are non-functional, asymptomatic, and smaller than 10 cm in diameter when incidentally detected. However, the presence of giant adrenal cysts, exceeding 10 cm in diameter, creates a diagnostic challenge due to the difficulty in determining their origin. Surgical intervention is advised when the cyst surpasses 10 cm in diameter, produces symptoms, causes endocrine abnormalities, exhibits intracystic bleeding, or raises suspicion of malignancy. The preferred treatment approach involves adrenalectomy, performed either through open surgery or laparoscopy. In cases where the diagnosis is unequivocal, ultrasound-guided percutaneous drainage serves as an alternative. Here, we present an exceptional case of a massive retroperitoneal mass caused by a rare giant adrenal cyst.

Multi-faceted dysregulated immune response for COVID-19 infection explaining clinical heterogeneity.

Clinical heterogeneity and varied prognosis are well noted for SARS-CoV-2 infection. Altered immune response is a major feature for the adverse prognosis however focus on altered immune response has been primarily limited to hyper-inflammatory responses like Cytokine storm. A deeper understanding of viral pathobiology and the interplay of innate and adaptive immune cells against SARS-CoV-2 infection is essential to optimize intervention strategy and future preparedness for SARS-CoV-2 or its related viral diseases. To uncover the immunological signatures driving the progression of SARS-CoV-2 infection, we performed an extensive immunophenotype on blood samples from 79 hospitalized patients with mild/moderate to severe infections as well as from healthy controls and recovered donors to understand the interplay between innate and adaptive responses impacting severity and prognosis. We observed multifarious immune dysregulation, varied across patients of the clinical spectrum. We observed 4 major dysregulations of immune phenotypes 1) depletion of M1φ (impaired antiviral response as APC), 2) immune suppression/exhaustion via activation of repressor like CD4+/CD8+PD1, TIM3, LAG3 3) inappropriate differentiation of lymphocyte (extreme elevated proportion of CD4 naive, memory B and T cells along with reduction of inflammatory activator like TLR2/4/TIGIT) and 4) cytokine storm. Our results show the identification of biomarkers to differentiate the different trajectories for SARS-CoV-2 infection.

One-year safety and effectiveness of insulin degludec in patients with diabetes mellitus in routine clinical practice in India-TRUST (Tresiba real-world use study).

Objective: This post-authorization safety study (PASS) was conducted to evaluate the long-term safety and effectiveness of insulin degludec in patients with diabetes mellitus (DM) requiring insulin therapy in routine clinical practice in India. Methods: Data on glycated hemoglobin (HbA1c) and adverse events (AEs) were collected up to 12 months after insulin degludec initiation. Results: A total of 1057 adult patients with DM were enrolled, including 60.07% males with the mean duration of 22.2 ± 21.90 years with type 1 DM and 10.1 ± 7.37 years with type 2 DM and the mean HbA1c of 9.6 ± 1.9%. Insulin degludec was prescribed to improve HbA1c and fasting plasma glucose (FPG). Insulin degludec daily dose was increased from 14.8 ± 8.0 U to 18.0 ± 9.46 U over 12 months resulting in a significant decrease of HbA1c by 1.8 ± 1.68% compared with baseline. There were 84 events of confirmed hypoglycemia in 51 patients during the 12-month follow-up period, and 44 AEs were reported in 2.6% of patients, of which 2 AEs were serious and unrelated to the drug. Conclusion: Insulin degludec is well tolerated in patients with DM. It improves glycemic control with reduced HbA1c, FPG, and postprandial glucose, with a low risk of hypoglycemia.

Practical aspects of usage of insulin in India: Descriptive review and key recommendations.

BACKGROUND AND AIMS: Insulin therapy is an integral part of diabetes management. However, reliable and easily accessible information on a number of basic facts concerning insulin therapy, including storage of insulin, managing insulin therapy during travel, nuances of insulin use while driving, and dose adjustments during sick days is lacking. This document aims to make readily available, reliable, and easy to implement information on these essential but relatively less discussed aspects of insulin therapy. METHOD: Literature search was performed using PubMed and Cochrane Library from inception till 1st of July 2019. The relevant topics were reviewed by a panel of 5 specialists and 23 contributing physicians and endocrinologists, who had assembled at Bengaluru, India for the 13th National Insulin Summit. After a thorough review of the literature, and following detailed discussions, the committee arrived at these recommendations. RESULTS: Unopened vials and cartridges of insulin should be stored at 2 °C-8 °C in a refrigerator and protected from direct sunlight. For opened vials and in-use cartridges, manufacturer's instructions must be followed at all times. While traveling by air, dose adjustments are required only when flying across more than five time zones in the east or west directions. Insulin therapy should not be omitted or stopped during an acute illness; rather the doses need careful adjustments based on self-monitoring of blood glucose. CONCLUSION: Recommendations and guidelines, covering many common aspects of insulin therapy are readily available. This consensus document aims to make recommendations for those essential aspects of insulin therapy that are crucial for its success but are relatively less known and less discussed.

Management of asymptomatic hyperuricemia: Integrated Diabetes & Endocrine Academy (IDEA) consensus statement.

AIM: The definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country. PARTICIPANTS: Ten members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus. EVIDENCE: A literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected. CONSENSUS PROCESS: Each participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting. CONCLUSION: Recommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia.

Sudden Renal Failure in a Scleroderma Patient: A Clinical Dilemma.

Scleroderma is a connective tissue disease which may present with renal crisis. But sometimes, acute renal failure in scleroderma may be due to a second pathology. We here present a case of a 35 year old woman with systemic sclerosis, who presented with acute renal failure. She was started treatment as a case of scleroderma renal crisis. But her condition continued to deteriorate and she also developed some cutaneous vasculitic lesions. Her urine also had active sediments. Finally, serology and kidney biopsy established the renal lesion as stage IV lupus nephritis. She responded to immunosuppressive regimen for lupus with rapid improvement of kidney function. Such overlap of scleroderma with lupus is very rarely reported.

Systemic Thrombolysis for Pulmonary Embolism: Evidence, Patient Selection, and Protocols for Management.

Acute pulmonary embolism presents a clinical challenge for optimal risk stratification. Although associated with significant morbidity and mortality at the population level, the spectrum of presentation in an individual patient varies from mild symptoms to cardiac arrest. Treatment options include anticoagulation, systemic thrombolysis, catheter-based interventions, and surgical embolectomy. In this article, an attempt is made to optimally identify patients who, based on available evidence, may benefit from systemic thrombolytic therapy. The clinical efficacy of systemic thrombolysis must be balanced against increased risks of major bleeding and intracranial hemorrhage.

Consensus on "Basal insulin in the management of Type 2 Diabetes: Which, When and How?"

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment. Appropriate initiation and intensification of insulin is critical for the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on basal insulin initiation and intensification, along with use of basal insulin in special situations (hepatic failure, renal failure and gestational diabetes mellitus). METHODS: Each consensus statement on basal insulin initiation, intensification and use of basal insulin in special situations was evaluated for dosing and titration based on established guidelines, data from approved pack inserts, prescribing information or summary of product characteristics for each insulin type, and published scientific literature. These evaluations were then factored into the national context based not only on the clinical experience of the expert committee representatives' but also based on the common therapeutic practices followed in India to successfully achieve optimal glucose control. RESULTS: Recommendations on initiation and intensification of basal insulin, and its use in special situations, have been developed. The key recommendations are to initiate basal insulin when 2 or 3 oral antidiabetic medications fail to achieve target glycaemic control, or in symptomatic patients with glycated haemoglobin value greater than 9%. Depending upon patient characteristics, any of the four available basal insulins [Neutral protamine Hagedorn (NPH), Glargine (IGlar), Detemir (IDet), Degludec (IDeg)] can be used. However, IDeg has a longer duration of action, comparatively lesser hypoglycaemia (both overall and nocturnal) and more flexibility in administration timing compared to IGlar) and IDet. Inability to maintain glycaemic control should lead to prompt intensification of basal insulin treatment by adding mealtime insulin, consisting of one to three injections of either rapid-acting insulin analog or regular insulin; depending upon patient characteristics, intensification can also be achieved by transition from basal insulin to twice daily premixed insulin analogs/premixed human insulin/insulin co-formulations. IDeg/IDet can be used in all grades of renal and hepatic impairment; and IDet has been approved for use in gestational diabetes mellitus. CONCLUSIONS: We hope that these consensus based recommendations shall be a useful reference tool for health care practitioners and help them in initiating and intensifying insulin therapy in T2DM patients in order to achieve optimal glycaemic control.

Glucagon-like peptide-1 receptor agonists favorably address all components of metabolic syndrome.

Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiology of cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome (MetS). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. MetS is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of MetS. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.

Observational study of effects of Saroglitazar on glycaemic and lipid parameters on Indian patients with type 2 diabetes.

Cardiovascular risk reduction is an important issue in the management of patients with Type 2 diabetes mellitus. Peroxisome proliferator activated receptor (PPAR) agonists favourably influence glycaemic and lipid parameters in patients with Type 2 diabetes and a dual PPAR agonist is expected to have favourable effect on both parameters. In this study we have analyzed the effect of Saroglitazar, a novel dual PPAR alpha &gamma agonist, on glycaemic and lipid parameters in Indian patients with Type 2 diabetes. After a mean follow-up period of 14 weeks in 34 patients, treatment with Saroglitazar, in a dose of 4 mg daily, resulted in significant improvement in both glycaemic and lipid parameters. There were significant mean reductions of fasting plasma glucose (36.71 mg/dl; p = 0.0007), post-prandial plasma glucose (66.29 mg/dl; p = 0.0005), glycosylated haemoglobin (1.13%; p < 0.0001), total cholesterol (48.16 mg/dl; p < 0.0001), low- density lipoprotein cholesterol (24.04 mg/dl; p = 0.0048), triglyceride (192.78 mg/dl; p = 0.0001), non-high density lipoprotein cholesterol (48.72 mg/dl; p < 0.0001) and the ratio of triglyceride and high density lipoprotein cholesterol (5.30; p = 0.0006). There was no significant change in body weight, blood pressure, high-density lipoprotein cholesterol and serum creatinine.

Vildagliptin with metformin once-daily regimen-insights from a single-center analysis.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have been well established as an adjunctive treatment to metformin. Most guidelines recommend treatment with a DPP-4 inhibitor, vildagliptin, in addition to metformin in a twice-daily regimen. However, the twice-daily regimen has difficulty with medication adherence, increased cost of therapy, and possibility of more side effects. Our objective was to evaluate, by means of retrospective analysis, the efficacy of once-daily metformin and vildagliptin (a DPP-4 inhibitor) in reducing blood glucose for patients on combination therapy. We analyzed data from our database of outpatients attending the diabetic clinic at a tertiary care center in Kolkata, India. We had data on once-daily combination of metformin and vildagliptin for 154 patients between September 2008 and May 2012. We followed up these patients for a median of 17.6 months and evaluated posttherapy glucose levels and hemoglobin A1c. Continuous variables were compared with t tests. Once-daily metformin-vildagliptin combination was found to be associated with a mean reduction of 27.52 mg/dL of fasting plasma glucose, 71.70 mg/dL of postprandial plasma glucose, and 1.41% reduction of HbA1c (P < 0.05 for all). Metformin-vildagliptin combination in a once-daily regimen seems to be associated with significant reductions in plasma glucose and HbA1c and may be a viable and cost-effective alternative to a twice-daily regimen as starting therapy.

Glycemic effects of vildagliptin and metformin combination therapy in Indian patients with type 2 diabetes: an observational study.

BACKGROUND: To analyze the glycemic response of Indian patients with type2 diabetes mellitus (T2DM) to combination therapy with vildagliptin and metformin and compare our data with those of clinical trials. METHODS: In a retrospective study of the hospital database, the glycemic control of 280 patients with T2DM who were either on a once- or twice-daily regimen of combination therapy with vildagliptin 50 mg and metformin 500 mg was analyzed. RESULTS: The mean duration of follow-up of the patients was 16.8 months. There was a reduction in fasting plasma glucose (FPG) of 1.52 ± 0.79 and 1.88 ± 0.87 mmol/L in the once- and twice-daily groups, respectively (both P < 0.0001) from baseline to last visit. The reduction in postprandial plasma glucose (PPPG) in the once- and twice-daily groups was 3.98 ± 1.72 and 4.33 ± 1.88 mmol/L, respectively (both P < 0.0001), whereas the reduction in HbA1c was 1.41 ± 1.39% and 1.90 ± 1.49%, respectively (both P < 0.0001). The differences in the reductions achieved in FPG and HbA1c with the two dosing regimens were significant. CONCLUSION: Although the present retrospective study shows a robust response to the combination of vildagliptin and metformin in Indian patients, more multicenter studies from India with a greater number patients are necessary to confirm this finding.

Ocular manifestations in children with cerebral palsy.

To evaluate the prevalence of ocular abnormalities among children with cerebral palsy, 140 patients with age between 6 months and 16 years were selected and the overall incidence of ocular abnormalities in this study was 42.1%. Two major ocular abnormalities identified in these cases were strabismus in 36.4%. Myopia was detected in 12.9% children while hypermetropia in 8.6% and astigmatism in 3.6% cases. Non-glaucomatous optic atrophy was present in 10.7% cases and nystagmus in 9.3% cases. Raised intra-ocular pressure was detected in 2.1% cases. Cortical visual impairment was seen in 20.7% children. Ocular abnormalities are frequent manifestations in cerebral palsy patients. Therefore, evaluation of all cerebral palsy cases emphasises the need for a full ophthalmological examination in order to detect ocular problems and to institute necessary therapy of the abnormalities for better livelihood of these physically challenged patients.