Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

INSTRUCTION: Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. METHODOLOGY: Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. RESULTS: Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). CONCLUSIONS: The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

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.

A Review of Oral Semaglutide Available Evidence: A New Era of Management of Diabetes with Peptide in a Pill Form.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have gained an important place in the management of diabetes management because of their exceptional glucose-lowering, weight lowering and cardiovascular (CV) benefits. Despite recommendations by various clinical practice guidelines and benefits, their usage in clinical practice was limited because of being injectable in nature. Oral semaglutide is a novel GLP-1RA with 94% homology to human GLP-1 which is co-formulated with absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), that overcomes the challenges of peptide absorption in the acidic conditions of the stomach. Oral semaglutide has been evaluated in an extensive phase 3 clinical trial programme named Peptide Innovation for Early Diabetes Treatment (PIONEER) which demonstrated its robust glucose and weight lowering effects against other comparators. The evolution of the GLP-1RA class to include an oral pill will facilitate the use of this class of agents much earlier in the diabetes treatment cascade owing to wider acceptance from patients and clinicians alike. The current review discusses the various aspects of oral semaglutide and its place in clinical practice.

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.

Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians.

The current diabetes management strategies not only aim at controlling glycaemic parameters but also necessitate continuous medical care along with multifactorial risk reduction through a comprehensive management concept. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of evolving antidiabetic agents that have the potential to play a pivotal role in the comprehensive management of patients with diabetes due to their diverse beneficial effects. SGLT2i provide moderate glycaemic control, considerable body weight and blood pressure reduction, and thus have the ability to lower the risk of macrovascular and microvascular complications. Some of the unique characteristics associated with SGLT2i, such as reduction in body weight (more visceral fat mass loss than subcutaneous fat loss), reduction in insulin resistance and improvement in ß-cell function, as measured by homeostatic model assessment-ß (HOMA-ß) could be potentially beneficial and help in overcoming some of the challenges faced by Indian patients with diabetes. In addition, a patient-centric approach with individualised treatment during SGLT2i therapy is inevitable in order to reduce diabetic complications and improve quality of life. Despite their broad benefits profile, the risk of genital tract infections, volume depletion, amputations and diabetic ketoacidosis associated with SGLT2i should be carefully monitored. In this compendium, we systematically reviewed the literature from Medline, Cochrane Library, and other relevant databases and attempted to provide evidence-based recommendations for the positioning of SGLT2i in the management of diabetes in the Indian population.Funding: AstraZeneca Pharma India Limited.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes.

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Prevalence of ultrasonography proved polycystic ovaries in North Indian women with type 2 diabetes mellitus.

BACKGROUND: Polycystic ovaries (PCO) and their clinical expression (the polycystic ovary syndrome [PCOS]) as well as type 2 diabetes mellitus (T2DM) are common medical conditions linked through insulin resistance. We studied the prevalence of PCO and PCOS in women with diet and/or oral hypoglycemic treated T2DM and non-diabetic control women. DESIGN: Prospective study. METHODS: One hundred and five reproductive age group women with diet and /or oral hypoglycemic treated T2DM were the subjects of the study. Sixty age-matched non-diabetic women served as controls. Transabdominal ultrasonographic assessment of the ovaries was used to diagnose PCO. Clinical, biochemical and hormonal parameters were also noted. RESULTS: Ultrasonographic prevalence of PCO was higher in women with diabetes than in non-diabetic subjects (61.0% vs. 36.7%, P < 0.003) whereas that of PCOS was 37.1% in diabetic subjects and 25% in non-diabetic controls (P > 0.1). Diabetic women with PCO had diabetes of significantly longer duration than those without PCO (4.19+/-2.0 versus 2.9+/-1.6 yrs; p < 0.05). Among both diabetic and non-diabetic women, those with PCO had significantly higher plasma LH, LH/FSH ratio, total testosterone and androstenedione levels. CONCLUSION: This study demonstrates a higher prevalence of PCO in women with T2DM as compared to non-diabetic subjects.

Clinical and endocrine aspects of pituitary tumors.

OBJECTIVE: To study the clinical spectrum and endocrine profile of pituitary tumors presenting to a tertiary care endocrine center. METHODS: Retrospective analysis of clinical and hormonal data of patients with pituitary tumors admitted in the Endocrinology Department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir India between January 1989 and December 1998. RESULTS: Over a period of one decade, 75 subjects were diagnosed to have pituitary tumors. Somatotroph adenoma was the most common pituitary mass lesion seen (44/75) and followed in the decreasing order of frequency, by non-functioning pituitary tumor (12/75), prolactinoma (11/75) and corticotroph adenoma (8/75). Overall there was a male preponderance (male to female ratio was 41:34). Subjects with somatotroph adenoma presented with classical features of acromegaly: mean fasting and post glucose suppression growth hormone levels were 34.04+/-11.67 and 36.47+/-6.64 ng/ml. Eleven subjects (9 females and 2 males) had prolactinoma; females presented with the classical symptom complex of amenorrhea-galactorrhea while males presented with headache, visual disturbances and impotence. The 12 subjects with nonfunctioning pituitary tumors presented with features of mass lesion. Of the 8 subjects (6 females and 2 males) with corticotroph adenomas, 2 were confirmed to have periodic hormonogenesis. CONCLUSION: In an endocrine center, functioning pituitary tumors are more often seen than non-functioning tumors.

Copper, zinc and magnesium levels in type-1 diabetes mellitus.

OBJECTIVE: Alterations in plasma concentrations of several trace elements have been reported to occur in type-1 diabetes mellitus. These micronutrients are suspected to have a role in pathogenesis and progression of the disease. METHODS: In a comparative analysis, the plasma concentration of copper, zinc and magnesium was estimated in 37 patients with type-1 diabetes mellitus and 25 healthy non-diabetic subjects at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India. Trace elements were estimated using a GBC 902 double beam atomic absorption spectrophotometer. RESULTS: Mean plasma concentrations of copper and magnesium were comparable between diabetic patients and control subjects. Plasma zinc levels were significantly higher (P=0.022) in diabetic patients (17.78 0.6 micromol/L) as compared to controls (15.80 0.75 micromol/L). Glycemic control and presence of microalbuminuria did not influence the plasma levels of copper, zinc and magnesium. CONCLUSION: Plasma zinc levels are significantly higher in type-1 diabetes mellitus patients, while plasma copper and magnesium levels are not significantly altered. No effect of sex, glycemic control or presence of microalbuminuria could be demonstrated on plasma concentration of trace elements in type-1 diabetes mellitus patients.

A revisit to prevailing care and challenges of managing diabetes in India: Focus on regional disparities.

An unprecedented rise in diabetes mellitus (DM) prevalence in India is the outcome of lifestyle changes in the background of genetic predisposition. Moreover, there are substantial regional variations in diabetes prevalence and management. The highest prevalence of DM was observed in southern region (Ernakulum, Kerala) and lowest prevalence was observed in North Eastern region (Manipur). Similarly large variations have been evident in overall awareness and diabetes care across the geographies within India. The regional challenges are largely affected by poor disease awareness, socioeconomic disparity and underutilization of the public health-care services. Though government has taken initiatives to address this issue, overall situation demands a collaborative effort from patients, health care professionals and the state. An exhaustive literature search was performed for articles and studies published on electronic databases. Present article assesses the regional disparity of diabetes epidemiology, current management practices and government policies for T2DM in India, identifies policy and research gaps, and suggests corrective measures to address the lacunae in diabetes care.

Recovery of prolactin function following spontaneous pregnancy in a woman with Sheehan's syndrome.

Sheehan's syndrome (SS) presents with hypopituitarism after parturition, usually preceded by postpartum hemorrhage. The first symptom of the disorder is lactation failure because of lactotroph cell necrosis. Recovery of lactotroph function after initial insult has not been reported in the literature. We describe the evaluation of a case of SS in whom lactotroph function recovered after the second pregnancy. A young woman delivered her first child at the age of 25 years; delivery was followed by severe postpartum hemorrhage and required blood transfusion. Sheehan's syndrome was diagnosed because of lactotroph, corticotroph, thyrotroph and somatotroph failure and empty sella on MRI. She conceived twice spontaneously and had normal lactation after the second delivery; investigations confirmed the normal basal and stimulable prolactin levels. We presume that recovery of lactotroph function after the second pregnancy in a patient with SS is possibly because of stimulatory effect of estrogen and progesterone on residual lactotroph cells.

Clinical biochemical and therapeutic aspects of diabetic ketoacidosis and its outcome.

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