Indian Reality of Clinical Practice and Patient Profile in Diabetes Care: Lessons from the IMPACT survey.

India shoulders a heavy burden of diabetes mellitus (DM), the management of which is suboptimal globally.& Objectives: Insulin Management: Practical Aspects in Choice of Therapy (IMPACT) survey was designed to gain insight into the ground (in-clinic) reality of DM management by physicians in India. METHODS: A survey consisting of 12 multiple-choice questions was conducted by SurveyMonkey® , focusing on practice profile, patient profile, and other aspects of DM management. RESULTS: The survey included 2424 physicians. Majority of them were general physicians (58.5%) followed by diabetologists (31.1%). Most (49.2%) of the respondents specified that the ideal time for a DM consultation is 15 min. However, 73.4% of them provided consultation of <10& min because of heavy patient load. Nearly half of the respondents reported that their patients consumed a diet with carbohydrate content of 60% to 80%, and 79.4% of them admitted that <50% of their patients adhered to dietary advice. About 73.5% of the respondents believed controlling fasting plasma glucose (FPG) level alone would not adequately control postprandial plasma glucose (PPG) level, and 93.0% of them preferred an insulin therapy at the initiation that controls both FPG and PPG levels. CONCLUSION: Limited consultation time, high-carbohydrate diet, and a need for choosing insulin regimens that provide control for both PPG and FPG levels are some ground realities of DM management in India. These realities need to be factored in while choosing treatment options to achieve the desired glycemic control and improve the status of diabetes care.

Overview of Clinical Trial Program and Applicability of Insulin Degludec/Insulin Aspart in Diabetes Management.

Insulin degludec/insulin aspart (IDegAsp) is the first soluble coformulation combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In patients with uncontrolled type 2 diabetes (T2DM) previously treated with insulins, IDegAsp twice daily effectively improves glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels with fewer hypoglycaemic episodes versus premix insulins. Further, insulin initiation with IDegAsp once daily provides superior long-term glycaemic control compared to insulin glargine with similar FPG and insulin doses, and numerically lower rates of overall and nocturnal hypoglycaemia. In patients with type 1 diabetes mellitus (T1DM), IDegAsp once daily and IAsp at remaining meals provides more convenient three injection regimen per day over conventional 4-5 injections based basal-bolus therapy. IDegAsp is an appropriate and reasonable option for intensifying insulin therapy in patients with T2DM and a relatively less complex treatment option for the management of T1DM.

Treating to target in type 2 diabetes: the BEGIN trial programme.

Insulin degludec is a new-generation basal insulin with an ultra-long duration of action. The insulin degludec and insulin degludec/insulin aspart clinical trial programme was truly global, involving 40 different countries and encompassing a multitude of ethnic populations. It is the largest insulin development clinical trial programme on record--with more than 11,000 patients included worldwide. It includes two main components: BEGIN (insulin degludec studied across the spectrum of diabetes) and BOOST (insulin degludec in a fixed-dose combination with insulin aspart). In clinical trials (phase 2 and phase 3a), insulin degludec achieved similar glycaemic control to that seen with insulin glargine in patients with type 1 or 2 diabetes, but with a lower risk of nocturnal hypoglycaemia. In addition, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes show the potential for adjusting the injection time, without compromising glycaemic control or safety. A 200 U/mL formulation of insulin degludec is also available for use in patients who require large volumes of basal insulin. Subcutaneous insulin degludec is generally well tolerated in patients with type 1 or 2 diabetes and represents a useful advance in the treatment of type 1 or 2 diabetes.

Two-year trends from the LANDMARC study: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcome in patients with type 2 diabetes mellitus.

INTRODUCTION: There are limited data on the real-world management of diabetes in the Indian population. In this 2-year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed. METHOD: This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlled/uncontrolled on ≥2 anti-diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan-India including metropolitan and non-metropolitan cities. RESULTS: Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (1096/6234); macrovascular complications were observed in 3.1% of patients (195/6234). Higher number of microvascular complications were noted in patients from non-metropolitan than in metropolitan cities (p < .0001). In 2 years, an improvement of 0.6% from baseline (8.1%) in mean glycated haemoglobin (HbA1c) was noted; 20.8% of patients met optimum glycaemic control (HbA1c < 7%). Hypertension (2679/3438, 77.9%) and dyslipidaemia (1776/3438, 51.7%) were the predominant CV risk factors in 2 years. The number of patients taking oral anti-diabetic drugs in combination with insulin increased in 2 years (baseline: 1498/6234 [24.0%] vs. 2 years: 1917/5763 [33.3%]). While biguanides and sulfonylureas were the most commonly prescribed, there was an evident increase in the use of dipeptidyl peptidase-IV inhibitors (baseline: 3049/6234, 48.9% vs. 2 years: 3526/5763, 61.2%). CONCLUSION: This longitudinal study represents the control of T2DM, its management and development of complications in Indian population. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2017/05/008452.

Observational Study on Outcomes after Radioiodine Ablation in Hyperthyroid Patients.

Introduction: Radio-active Iodine (RAI) is a safe, definitive, and cost-effective modality of treatment that is used as the first line of treatment for Graves' hyperthyroidism by most endocrinologists. Very few reports are available from India, observational follow-up data is needed to determine the meaningful prognostic outcomes of RAI ablation in the Indian population. Aims: To study the outcomes in hyperthyroid patients undergoing RAI ablation. Materials and Methods: This observational cohort study was conducted at Department of Endocrinology at Indraprastha Apollo Hospital, New Delhi. A total of 82 hyperthyroid patients who underwent RAI ablation between June 2014 to June 2018 were enrolled. RAI dose was calculated arbitrarily in most cases; often by an empirical fixed dose based on the goiter size and RAIU. The patients were reviewed at 1, 3 and 6 months post-RAI ablation. During follow-up, along with a detailed clinical examination, free T4, free T3 and TSH were checked. Results: The dose of I-131 varied from 6 mCi to 14 mCi. Most of the patients were given RAI in the dose of 7.1-10 mci. About 63.4% of patients achieved hypothyroidism in 6 months, 6.1% in 1 month, 37.8% in 3 months, and 19.5% in 6 months. Gender, age, etiology of hyperthyroidism, baseline thyroid function, goiter, and ophthalmopathy did not affect outcomes after RAI ablation. Those who were not treated with antithyroid drugs prior to RAI therapy were found to have higher rates of conversion to a hypothyroid state. Conclusion: RAI can be given safely as the first line of treatment in Graves' disease and antithyroid drug naïve patients respond better to therapy.

One-year trends from the LANDMARC trial: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcomes of type 2 diabetes mellitus.

INTRODUCTION: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first-of-its-kind, pan-India, prospective, observational study aimed to evaluate real-world patterns and management of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. The first-year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non-metropolitan cities are reported here. RESULTS: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non- metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: -0.5% vs. -0.5%; p = .8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p < .0001) higher in non-metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti-diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase-IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p < .0001) higher in the insulin vs. the insulin-naïve subgroups; in the insulin-naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs. CONCLUSIONS: First-year trends of the LANDMARC study offer insights into real-world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM.

Baseline characteristics of participants in the LANDMARC trial: A 3-year, pan-india, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

INTRODUCTION: Longitudinal data on progression, complications, and management of type 2 diabetes mellitus (T2DM) across India are scarce. LANDMARC (CTRI/2017/05/008452), the first pan-India, longitudinal, prospective, observational study, aims to understand the management and real-world outcomes of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrollment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. Baseline characteristics were analyzed using descriptive statistics. RESULTS: Of the 6279 recruited participants, 6236 were eligible for baseline assessment (56.6% [n/N = 3528/6236] men; mean ± SD age: 52.1 ± 9.2 years, diabetes duration: 8.6 ± 5.6 years). mean ± SD HbA1c, fasting plasma glucose, and postprandial glucose values were 64 ± 17 mmol/mol (8.1 ± 1.6%), 142.8 ± 50.4 mg/dl, and 205.7 ± 72.3 mg/dl, respectively. Only 25.1% (n/N = 1122/6236) participants had controlled glycemia (HbA1c < 53 mmol/mol, <7%). Macrovascular and microvascular complications were prevalent in 2.3% (n/N = 145/6236) and 14.5% (n/N = 902/6236) participants, respectively. Among those with complications, non-fatal myocardial infarction (n/N = 74/145, 51.0%) and neuropathy (n/N = 737/902, 81.7%) were the most reported macrovascular and microvascular complication, respectively. Hypertension (n/N = 2566/3281, 78.2%) and dyslipidemia (n/N = 1635/3281, 49.8%) were the most reported cardiovascular risks. Majority (74.5%; n/N = 4643/6236) were taking oral anti-diabetic drugs (OADs) only, while 24.4% (n/N = 1522/6236) participants were taking OADs+insulin. Biguanides (n/N = 5796/6236, 92.9%) and sulfonylureas (n/N = 4757/6236, 76.3%) were the most reported OADs. Basal (n/N = 837/6236, 13.4%) and premix (n/N = 684/6236, 11.0%) insulins were the most reported insulins. CONCLUSIONS: Baseline data from LANDMARC help understand the clinical/medical profile of study participants and underscore the extent of suboptimal glycemic control and prevalence of associated complications in a vast majority of Indians with T2DM.

Forum for Injection Technique and Therapy Expert Recommendations, India: The Indian Recommendations for Best Practice in Insulin Injection Technique, 2017.

Health-care professionals in India frequently manage injection or infusion therapies in persons with diabetes (PWD). Patients taking insulin should know the importance of proper needle size, correct injection process, complication avoidance, and all other aspects of injection technique from the first visit onward. To assist health-care practitioners in their clinical practice, Forum for Injection Technique and Therapy Expert Recommendations, India, has updated the practical advice and made it more comprehensive evidence-based best practice information. Adherence to these updated recommendations, learning, and translating them into clinical practice should lead to effective therapies, improved outcomes, and lower costs for PWD.

Prevalence of glucose intolerance at 6 weeks postpartum in Indian women with gestational diabetes mellitus.

AIMS: Women with a history of gestational diabetes mellitus (GDM) have an increased risk for future glucose intolerance, and should be followed up with subsequent screening for the development of diabetes or pre-diabetes at 6-12 weeks postpartum. We studied the prevalence of glucose intolerance at 6 weeks postpartum in Indian women with GDM diagnosed according to ADA criteria. MATERIALS AND METHODS: This longitudinal study, conducted at a tertiary care centre, included 75 Asian-Indian women aged ≥18 years, with a diagnosis of GDM (as per ADA criteria), who were referred to the Endocrine Department at Indraprastha Apollo Hospital, Delhi. A 2-h 75 g oral glucose tolerance test (OGTT) was performed at 6 weeks postpartum. RESULTS: Out of the 75 women who had GDM and were recommended an OGTT at 6 weeks postpartum, 17.3% did not return for the test. Out of 62 women, one-third (33.8%) developed an abnormal OGTT at 6 weeks postpartum, while 66.1% had reverted to normal glucose tolerance. Impaired fasting glucose (IFG) was seen in 14.5%, 4.8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 6.4% had overt type 2 diabetes. CONCLUSION: Our study emphasizes the need for compulsory follow up OGTT for women with GDM in our part of the world in view of ethnicity and prevailing socio-cultural factors.

Forum for Injection Technique (FIT), India: The Indian recommendations 2.0, for best practice in Insulin Injection Technique, 2015.

As injectable therapies such as human insulin, insulin analogs, and glucagon-like peptide-1 receptor agonists are used to manage diabetes, correct injection technique is vital for the achievement of glycemic control. The forum for injection technique India acknowledged this need for the first time in India and worked to develop evidence-based recommendations on insulin injection technique, to assist healthcare practitioners in their clinical practice.

Treat-to-target trials in diabetes.

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

Barriers and solutions to diabetes management: An Indian perspective.

India, with one of the largest and most diverse populations of people living with diabetes, experiences significant barriers in successful diabetes care. Limitations in appropriate and timely use of insulin impede the achievement of good glycemic control. The current article aims to identify solutions to barriers in the effective use of insulin therapy viz. its efficacy and safety, impact on convenience and life-style and lack of awareness and education. Therapeutic modalities, which avoid placing an undue burden on patients' life-style, must be built. These should incorporate patient-centric paradigms of diabetes care, team-based approach for life-style modification and monitoring of patients' adherence to therapy. To address the issues in efficacy and safety, long-acting, flat profile basal insulin, which mimics physiological insulin and show fewer hypoglycemic events is needed. In addition, therapy must be linked to monitoring of blood glucose to enable effective use of insulin therapy. In conjunction, wide-ranging efforts must be made to remove negative perception of insulin therapy in the community. Patient- and physician - targeted programs to enhance awareness in various aspects of diabetes care must be initiated across all levels of health-care ensuring uniformity of information. To successfully address the challenges in facing diabetes care, partnerships between various stakeholders in the care process must be explored.

What the future holds for gliptins.

Gliptins have revolutionised the treatment of Type 2 Diabetes Mellitus, addressing the hyperglycemia through its effects on the alpha and beta cells of the pancreas. In this article,we review the extra-glycemic effects of gliptins on central nervous system, cardiovascular biology and the bone health and concerns regarding pancreatitis and pancreatic cancer.

Cathepsin-D, adiponectin, TNF-α, IL-6 and hsCRP plasma levels in subjects with diabetic foot and possible correlation with clinical variables: a multicentric study.

Diabetic foot, characterized by a pronounced inflammatory reaction, decreased collagen content and biosynthesis and accelerated degradation are crucial in wound healing. Cathepsin D, an aspartic endopeptidases implicated in cell growth, apoptosis, and its inhibitor has been reported to reverse the inhibition of collagen biosynthesis in wounded rat skin with diabetes. To date, the increased proteolytic activity of Cathepsin D in diabetic foot has not been evaluated and the pathogenic significance of the inflammation has received little attention. Of the patients [with ulcer (n=211) and without ulcer (n=208)], 89.73% had type 2 diabetes. Subjects with diabetic foot ulcer showed higher median plasma level of Cathepsin D [556.3 (312.6-587.3) RFC/ml vs 306.3 (92.6-337.3) RFC/ml], TNF-α [96.6 (79.9-121.5) ng/ml vs 8.4 (7.1-9.20) ng/ml], IL-6 [32.2 (8.52-48.4) ng/ml vs 4.9 (4.5-5.6) ng/ml], hsCRP [12.6 (11.2-14.1) mg/ml vs 3.90 (3.50-4.60) mg/ml] and lower median plasma levels of adiponectin [8.50 (7.10-9.5) ng/ml vs 13.3 (12.1-14.2) ng/ml]. A positive correlation was found between grades of ulcer, BMI, A1c and retinopathy for Cathepsin D, for adiponectin, between grades of ulcer, BMI, retinopathy, nephropathy & smoking, for IL-6, between grades of ulcer, BMI, nephropathy, CAD & smoking, for hsCRP, grades of ulcer, BMI, LDL-C, nephropathy & smoking, while total cholesterol, nephropathy, PAD, smoking and neuropathy for TNF-α.

Forum for injection techniques, India: the first Indian recommendations for best practice in insulin injection technique.

Advances in the treatment of diabetes have led to an increase in the number of injectable therapies, such as human insulin, insulin analogues, and glucagon-like peptide-1 analogues. The efficacy of injection therapy in diabetes depends on correct injection technique, among many other factors. Good injection technique is vital in achieving glycemic control and thus preventing complications of diabetes. From the patients' and health-care providers' perspective, it is essential to have guidelines to understand injections and injection techniques. The abridged version of the First Indian Insulin Injection technique guidelines developed by the Forum for Injection Technique (FIT) India presented here acknowledge good insulin injection techniques and provide evidence-based recommendations to assist diabetes care providers in improving their clinical practice.