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.

Protein restriction in adults with chronic kidney disease, with or without diabetes: Integrated Diabetes and Endocrine Academy (IDEA) consensus statement for Indian patients.

BACKGROUND AND AIMS: Most guidelines recommend protein restriction in adults with chronic kidney disease (CKD), with or without diabetes. However, advising protein restriction for every person with CKD is controversial. We aim to arrive at a consensus on this topic, especially among Indian adults with CKD. METHODS: A systematic literature search in the PubMed electronic database was undertaken using specific keywords and MeSH terms until May 1, 2022. All the retrieved literature was circulated and rigorously deliberated upon by the panel members. RESULTS: Seventeen meta-analyses that evaluated the outcomes of protein restriction in adults with CKD, with or without diabetes, met our inclusion criteria and were analyzed. A low-protein diet (LPD) in people with stages 3-5 of CKD (who are not on haemodialysis [HD]) reduces the severity of uremic symptoms and the rate of decline in glomerular filtration rate, leading to a delay in dialysis initiation. However, LPD in patients on maintenance HD may not be desirable because HD-induced protein catabolism may lead to protein-energy malnutrition. Since the average protein intake among Indians is much lower than recommended, this must be taken into consideration before recommending LPD for all Indian adults with CKD, particularly those on maintenance HD. CONCLUSION: It is essential to assess the nutritional status of people with CKD, particularly in countries like India where average daily protein intake is poor, before recommending guideline-directed protein restriction. The prescribed diet, including the quantity and quality of proteins, should be tailored to the person's habits, tastes, and needs.

Testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism -an Integrated Diabetes and Endocrine Academy (IDEA) consensus guideline.

BACKGROUND: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. METHODS: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. RESULTS: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. CONCLUSION: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Assessing prevalence and predictors of depression in Type 2 Diabetes Mellitus (DM) patients - The DEPDIAB study.

OBJECTIVES: Depression is common in diabetes and has significant impact on health outcomes. Suicidal ideation also forms a part of the spectrum of diabetes and coexistent depression. To assess the predictors of depression as well as its prevalence in Type 2 Diabetes Mellitus (T2DM) patients, we conducted a cross sectional study entitled "DEPression in DIABetes" (DEPDIAB). MATERIAL AND METHODS: A cohort of consecutive 1371 T2DM patients from Eastern India suffering from diabetes greater than 1 year was assessed in a cross- sectional survey in 9 different hospitals and medical polyclinics in Kolkata, India for depression by administering the 9-item PHQ - 9 and Beck depression scales. Socioeconomic status was assessed by the "Revised Kuppuswamy and B G Prasad socio-economic scales for 2016", a validated scoring system for assessing the socioeconomic status of Indian patients. RESULTS: In our study 836 patients (60.9%) were male and 535 (39.02%) were female. 56 patients (4.1%) met the criteria for major depression and 494 patients (36.16%) for minor depression. No sign of depression was found in 816 patients (59.74%). Depression was strongly associated with younger age (18-40 years vs. >60 years) [OR-2.09; 95% CI 1.11-3.96], female sex [OR-1.31; 95% CI 1.11-2.01], low socioeconomic status [OR-2.69; 95% CI 1.34-3.79], poor compliance [OR- 5.05; 95% CI 2.79-8.13], hypoglycemia [OR 1.466; 95% CI 1.076-1.999] and difficulty in managing day-to-day activities [OR- 4.648; 95% CI 3.450-6.262] Suicidal ideation was detected in 201 patients (14.8%). Among patients who had repeated attacks of hypoglycemia (>1 episode per month), 22% experienced suicidal ideation. This was significantly higher than in patients who had not suffered from hypoglycemia (12%) (p < 0.0001). Patients with HbA1C of 7% or lower experienced statistically significantly lesser suicidal ideation than patients with a higher HbA1C (12% vs. 16.8% {p = 0.016}). Suicidal ideation did not correlate withbody mass index (BMI), fasting plasma glucose (FPG) or insulin usage. CONCLUSIONS: We found a high prevalence of depression in T2DM patients in Eastern India. Younger age, female sex, lower socio-economic status, poor compliance, hypoglycemia, and difficulty in managing day to day activities emerged as significant predictors of depression in this study. Recurrent episodes of hypoglycemia were an independent risk factor for suicidal ideation in patients with depression. Depression was not significantly associated with co morbidities associated with T2D and surprisingly insulin usage was not associated with increased depression.

Expert Group Recommendations on the Effective Use of Bolus Insulin in the Management of Type 2 Diabetes Mellitus.

Evidence suggests a major contribution of postprandial glucose (PPG) excursions to the increased risk of micro- and macro-vascular complications in individuals with type 2 diabetes mellitus (T2DM). Administration of bolus insulin remains a very effective therapeutic option for PPG control. The aim of this expert group recommendation document was to provide practical and easy-to-execute guidelines for physicians on the appropriate use of bolus insulin in the management of T2DM. A panel of key opinion leaders from India reviewed and discussed the available clinical evidence and guideline recommendations on the following topics: (1) optimum control of PPG; (2) choice of bolus insulin; and (3) special situations and practical considerations. The expert panel critically analyzed the current literature and clinical practice guidelines and factored their rich clinical experience to develop a set of nine expert group recommendations for the effective use of bolus insulin. These recommendations will not only result in a more evidence-based application of bolus insulin in the clinical setting but also trigger further research and provide a valuable base for the development of future guidelines on the use of bolus insulin in the management of individuals with T2DM.

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.

Safety of Insulin Degludec/Insulin Aspart in Patients with Diabetes Mellitus over a Period of 1 Year during Routine Clinical Care in India: SMART (Study of Management of Diabetes with Ryzodeg™ Treatment).

This post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (IDegAsp) in adult patients with diabetes mellitus (DM) during routine clinical care under a real-world setting in India. Eligible patients received IDegAsp for a minimum of 12 months during routine clinical management. Data were collected at 0, 3, 6, and 12 months. In total, 1029 adult patients with DM were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. Thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to IDegAsp use. At baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. At 12 months of treatment with IDegAsp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. Mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. This study showed the safety of IDegAsp in patients with diabetes mellitus over a period of 1 year during routine clinical care.

From Individualized to Personalized Medicine in Diabetes: An Expert Overview.

Personalized medicine is an individualized and stratified approach to the management of a disease. Personalized medicine can reform the prevention, prediction, and management of diabetes. Use of genetic information in polygenic and monogenic forms of diabetes can help to identify genetic variants and reclassify patients into pathophysiological subgroups. Targeted diagnostic, preventive, and therapeutic interventions can be defined for these groups for effective management of diabetes. Pharmacogenetics combines genotypic and phenotypic factors to develop personalized care in various pathophysiological subgroups of persons with diabetes. Personalized medicine finds wider utility in monogenic (especially Maturity Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus [NDM]) than in polygenic, diabetes. The most frequently mutated genes in MODY include HNF1A and HNF3A. the common genes responsible for NDM include KCNJ11 and ABCC8 (SUR) genes. These genes influence various aspects of glucose metabolism such as ß-cell K-ATP channel modulation, production of insulin and development of pancreas. The Madras Diabetes Research Foundation has fostered research in personalized medicine for diabetes based upon genetic information and has developed a national registry for neonatal diabetes and other monogenic form of diabetes.

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.

Consensus on Initiation and Intensification of Premix Insulin in Type 2 Diabetes Management.

INTRODUCTION: Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. OBJECTIVE: The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic. METHODS: A meeting of experts from across India was conducted at Chennai in July 2016. The expert committee evaluated each premix insulin regimen with reference to 1) Current recommendations by various guidelines, 2) Approved pack inserts and 3) Published scientific literature. The information was debated and discussed within the expert group committee, to arrive at seven consensus-based recommendations for initiation and intensification with premix insulin. RESULTS: Recommendations based on consensus on initiation and intensification of premix insulin in type 2 diabetes mellitus (T2DM) management were developed for the following situations. 1) Initiation of premix insulin co-formulation at diagnosis, 2) Initiation of once daily (OD) premix insulin/co-formulation, 3) Initiation of twice daily (BID) premix insulin/co-formulation 4) Intensification with BID and thrice daily (TID) premix insulin/co-formulation. Three recommendations pertained to the use of premix insulin in other forms of diabetes, or in specific situations: 5) Use of premix insulin in gestational diabetes mellitus 6) Use of premix insulin in type 1 Diabetes Mellitus (T1DM) 7) Premix insulin use during Ramadan. CONCLUSIONS: In the setting of high carbohydrate consumption in India, or in patients with predominant post prandial hyperglycemia, premix insulin/co-formulation can offer effective and convenient glycemic control. This paper will help healthcare practitioners initiate and intensify premix insulin effectively.

Hypoglycemia: The neglected complication.

Hypoglycemia is an important complication of glucose-lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycemic control invariably increases the risk of hypoglycemia. A six-fold increase in deaths due to diabetes has been attributed to patients experiencing severe hypoglycemia in comparison to those not experiencing severe hypoglycemia Repeated episodes of hypoglycemia can lead to impairment of the counter-regulatory system with the potential for development of hypoglycemia unawareness. The short- and long-term complications of diabetes related hypoglycemia include precipitation of acute cerebrovascular disease, myocardial infarction, neurocognitive dysfunction, retinal cell death and loss of vision in addition to health-related quality of life issues pertaining to sleep, driving, employment, recreational activities involving exercise and travel. There is an urgent need to examine the clinical spectrum and burden of hypoglycemia so that adequate control measures can be implemented against this neglected life-threatening complication. Early recognition of hypoglycemia risk factors, self-monitoring of blood glucose, selection of appropriate treatment regimens with minimal or no risk of hypoglycemia and appropriate educational programs for healthcare professionals and patients with diabetes are the major ways forward to maintain good glycemic control, minimize the risk of hypoglycemia and thereby prevent long-term complications.