Diabetes in India's North East Study: Prevailing Insulin Usage and Insulin Injection Practices amongst Type 2 Diabetes Mellitus Patients.

OBJECTIVE: Insulin therapy is mostly advised in patients with poorly controlled type 2 diabetes mellitus (T2DM). However, wide variation exists in insulin practice and usage across the Indian geography. MATERIALS AND METHODS: In this cross-sectional study, a retrospective audit of the medical records of T2DM patients who were receiving insulin and attending an urban referral clinic in Northeast India during the period from 2006 to 2017 was conducted to analyze the insulin utilization pattern and injection technique variation. A total of 1,454 patients were included, 60% were male and 40% were female. RESULTS: At presentation, the mean duration of T2DM was 12.13 (7.45) years. Insulin with or without oral anti-diabetic (OADs) was received by 52.27% and 47.73% of patients, respectively. The majority (62.93%) used a pen device for insulin administration. The patient-reported reasons for insulin therapy initiation were OAD failure (33.15%), glucotoxicity (30.26%) and diabetesassociated complications (20.36%). The mean ± standard deviation (SD) total daily dose (TDD) of insulin was 33.05 ± 17.09 (0.53 ± 0.30 units/kg/day). The breakup for the number of injection(s) per day was one (234,16.09%), two (970,66.71%), three (166,11.42%), four (78, 5.36%), and five (6, 0.41%). The majority (67.88%) used premixed insulin, while 10.90% used basal insulin alone. Compared to those without lipohypertrophy (LH), patients with LH were less likely to rotate the site of injection (0.85 vs 17.90%; p = 0.000), space the injections (10.71 vs 23.91%; p = 0.000), injected less often in correct site (7.81 vs 29.0%; p = 0.000), more likely to use wrong angles (10.08 vs 22.73%; p = 0.000) and reuse the needles (5.63 vs 14.86%; p = 0.000). Also, 34.87% of patients were not storing their insulin device at the right temperature and 8.87% experienced at least one episode of a hypoglycemic event. CONCLUSION: This audit depicts important attributes of current injection practices amongst T2DM patients on insulin and suggests the possible benefits of adopting correct practices for avoiding complications such as LH and hypoglycemia.

The Bariatric Pyramid: A framework for therapeutic targets.

The Bariatric Pyramid is a model which serves to explain the goals of obesity management, act as a milestone for monitoring of therapy, and to benchmark the utility of various anti-obesity medications and interventions. Built upon a base of sustainability, it lists three more desired aspects of care: sufficiency (sufficient strength) safety and security. Each of the four aspects of the pyramid: sustainability, sufficiency safety and security have three angles, which allows the reader to understand them easily. The model that we propose is useful in training health care professionals, in therapeutic patient education, for assessing various anti-obesity therapies, and in reaching the right decision while managing obesity.

An Expert Group Consensus Statement on "Approach and Management of Prediabetes in India".

The prevalence of prediabetes, a forerunner of diabetes is very high, and its conversion to diabetes is also more rapid among Asian Indians. Prediabetes also predisposes to the development of macrovascular and to a lesser extent of microvascular complications of diabetes. In a large community-based epidemiological study, the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB), data reported an overall prevalence of prediabetes of 10.3%, derived from 15 Indian states. This shows that the diabetes epidemic is far from over as many of them may soon convert to diabetes. Prediabetes, however, should not be considered a path to diabetes rather it should be a window of opportunity for the prevention of diabetes. This early screening, detection, and treatment of prediabetes should be made a national priority. Several countries have introduced lifestyle programs to prevent diabetes and, when indicated, pharmacological intervention with metformin as well. This consensus statement outlines the approaches to screening and lifestyle and pharmacological management of prediabetes in Asian Indians.

Determination of individual type 2 diabetes risk profile in the North East Indian population & its association with anthropometric parameters.

Background & objectives: Diabetes genomics research has illuminated single nucleotide polymorphism (SNP) in several genes including, fat mass and obesity associated (FTO) (rs9939609 and rs9926289), potassium voltage-gated channel subfamily J member 11 (rs5219), SLC30A 8 (rs13266634) and peroxisome proliferator-activated receptor gamma 2 (rs1805192). The present study was conducted to investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes (T2D) in the North East Indian population, and also to establish their association with anthropometric parameters. Methods: DNA was extracted from blood samples of 155 patients with T2D and 100 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. To confirm the association between the inheritance of SNP and T2D development, logistic regression analysis was performed. Results: For the rs9939609 variant (FTO), the dominant model AA/(AT+TT) revealed significant association with T2D [odds ratio (OR)=2.03, P=0.021], but was non-significant post correction for multiple testing (P=0.002). For the rs13266634 variant (SLC30A 8), there was considerable but non-significant difference in the distribution pattern of genotypic polymorphisms between the patients and the controls (P=0.004). Significant association was observed in case of the recessive model (CC+CT)/TT (OR=4.56 P=0.001), after adjusting for age, gender and body mass index. In addition, a significant association (P=0.001) of low-density lipoprotein (mg/dl) could be established with the FTO (rs9926289) polymorphism assuming dominant model. Interpretation & conclusions: The current study demonstrated a modest but significant effect of SLC30A8 (rs13266634) polymorphisms on T2D predisposition. Considering the burgeoning prevalence of T2D in the Indian population, the contribution of these genetic variants studied, to the ever-increasing number of T2D cases, appears to be relatively low. This study may serve as a foundation for performing future genome-wide association studies (GWAS) involving larger populations.

Thyroid Emergencies: New Insight into Old Problems.

Thyroid emergencies are major life-threatening endocrine conditions associated with life-threatening disorders resulting from either severe deficiency or excess of thyroid hormones. Deficiency of thyroid hormones may present as myxedema coma whereas excessive hormone production can present as life threatening thyrotoxic storm. The diagnosis of both requires a high index of clinical suspicion. Thyroid storm, in spite of accurate diagnosis, continues to have high fatality, whereas myxedema management has markedly improved with advancement in intensive care facility. The key to successful management of these emergencies is timely diagnosis and management by experienced physician in an intensive care setting. This article discusses the basic differences of both entities with an attempt to appropriate recognition and awareness of clinical signs and symptoms, highlight the salient diagnostic points and delineate the rational approach, which can lead to appropriate treatment at the earliest and reduce mortality.

Blood Pressure Variability in Patients with Diabetes Mellitus with Hypertension: Treatment Recommendations and Role of Amlodipine.

Recently, blood pressure variability (BPV) has gained focus owing to its role in predicting cardiovascular (CV) outcomes. Additionally, alterations in BPV contribute to the progression of end organ damage and trigger vascular events in hypertensive patients. Therefore, amelioration of BPV is considered a potentially important target and different classes of drugs are used to achieve the desired blood pressure (BP) goal. Based on several studies and clinical trials, treatments with CCB such as amlodipine have been found to be most effective in the management of BPV in hypertensive patients with diabetes. Growing evidence substantiates the role of amlodipine in significant reduction of BPV, thus, lowering the risk of diabetes related complications. This review sheds light on the importance of BPV reduction and the effectiveness of amlodipine in preventing cardiovascular morbidity and mortality in hypertensive patients with diabetes.

Autoimmune Hypophysitis Presenting as Solid-Cystic Mass Managed Conservatively.

BACKGROUND: Autoimmune hypophysitis (AH) is a rare inflammatory condition of the pituitary gland and usually affects women of childbearing age. It commonly leads to pituitary dysfunction. Moreover, pituitary enlargement may lead to compressive symptoms, which necessitates urgent surgical decompression. Resection of the pituitary gland causes iatrogenic hypopituitarism which requires lifelong hormonal supplementation. With an increasing number of suspected cases of pituitary diseases, there has been a paradigm shift in the management by conservative measures, especially, when surgery is not urgently needed. CASE REPORT: We report a case of AH in a premenopausal woman presenting with headache. MRI revealed a solid-cystic mass involving the anterior lobe of the pituitary gland. The infundibulum was also thickened and enhancing; however, it was still in the midline. Ancillary MRI findings and hormonal profile were favouring the diagnosis of AH over pituitary neoplasm. The patient was managed conservatively with high doses of glucocorticoids, which resulted in prompt resolution of the lesion. During subsequent follow-up over 6 years, there was no recurrence and partial restoration of the pituitary function was seen. This case is interesting due to an unusual MRI appearance of AH, presenting as a solid-cystic mass. Moreover, disease resolution with conservative treatment strengthens the approach to limit surgery to those patients with compressive symptoms or uncertain diagnosis. CONCLUSIONS: AH should be included in the differential diagnosis of solid-cystic pituitary masses along with clinical correlation, which includes early involvement of ACTH and TSH and a relatively rapid development of hypopituitarism. In uncertain cases or with lack of compressive symptoms, a trial of steroids is worthwhile.

Interdisciplinary position statement on management of hyperglycemia in peri-operative and intensive care.

Hospitalized patients with diabetes pose numerous clinical challenges, including hyperglycemia, which may often be difficult to control. The therapeutic challenges are further accentuated by the difficulty in practical application of existing guidelines among Indian and South Asian patients. The present review highlights the various clinical challenges encountered during management of different diabetic hospitalized populations, and attempts to collate a set of practical, patient and physician friendly recommendations to manage hyperglycemia in such patients.

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.

Addendum 1: Forum for Injection Technique and Therapy Expert Recommendations, India.

With the emerging complexities in chronic diseases and people's lifestyles, healthcare professionals (HCPs) need to update their methods to manage and educate patients with chronic lifestyle disorders, particularly diabetes. The insulin injection technique (IIT), along with various parameters, must also be updated with newer methods. Forum for Injection Technique and Therapy Expert Recommendations (FITTER), India, has updated its recommendations to cover newer ways of detecting hypoglycaemia and lipohypertrophy, preventing needlestick injuries (NSIs), discouraging the reuse of insulin needles and encouraging good disposal. FITTER, India, is also introducing recommendations to calculate insulin bolus dose. These updated recommendations will help HCPs better manage patients with diabetes and achieve improved outcomes.

C-Reactive Protein Level can be a Better Indicator than Erythrocyte Sedimentation Rate in Assessing the Severity of Inflammation and Guiding Glucocorticoid Therapy in Subacute Thyroiditis.

Background: Despite the widespread use of several diagnostic tests in subacute thyroiditis (SAT), their usage remains largely subjective. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are useful indicators of inflammation in patients with SAT. The purpose of this study was to compare the scope for utilising CRP and ESR objectively in deciding the requirement of glucocorticoid therapy. Methods: A total of 28 patients with SAT were included in this study. Serum CRP and ESR were measured in all the patients. The characteristics of these tests were assessed firstly by using previously accepted positivity criterion for the particular diagnostic test. The area under the receiver operating characteristics (ROC) curve was obtained to provide an index of the overall discriminative ability of both tests. Results: Fifteen out of 28 patients were found to have features of significant thyroid inflammation eventually requiring glucocorticoid based on the current recommendations. The mean CRP value was significantly higher in patients requiring glucocorticoids. The ROC curves indicated that the optimal positivity criterion was 19.3 mg/L for the CRP level and 46 mm at the 1st hour for ESR. CRP with a sensitivity of 0.67, a specificity of 0.92, a positive likelihood ratio of 8.67, and an accuracy of 0.64 appeared better than ESR, which showed a sensitivity of 0.93, a specificity of 0.53, a positive likelihood ratio of 2.02, and an accuracy of 0.60. Conclusions: The serum CRP level provided a clear advantage over ESR in the assessment of the severity of inflammation before initiation of glucocorticoid therapy in SAT. However, a well-powered study is needed to examine the clinical relevance of such a role for CRP in thyroidology.

Incorporating Integrated Personalised Diabetes Management (iPDM) in Treatment Strategy: A Pragmatic Approach.

Diabetes is a global public health concern. Vigilant monitoring and effective management of glycaemic variations are essential to prevent complications of diabetes. Effectively incorporating monitoring strategies in management of diabetes is a serious challenge. Patient-centered approach is necessary to customise monitoring and therapy of diabetes. This has been made possible by integrating technology with personalised therapeutic strategy. The integrated personalised diabetes management (iPDM) is a holistic, patient-centered approach that focuses on personalising diabetes management to streamline therapy and improve outcome. iPDM helps strengthen the care process, facilitates communication between patients and their healthcare team, and integrates digital tools that visualise and analyse data. The five E's which includes enthusiasm, education, expertise, empathy and engagement are the key pillars of a strong foundation for the iPDM model. iPDM model is a convenient and easily accessible tool that shifts the management paradigm from an "algorithmic" to "personalized" care to optimise treatment outcomes. Structured self-monitoring of blood glucose (SMBG) should be available as part of the self-management process for people with sub-optimally controlled type 2 diabetes, including those not on insulin therapies. Different SMBG regimens should be followed based on factors such as diabetes type, treatment approach (diet, oral antidiabetic medication, or insulin), glycaemic control, available resources, and patient's level of education.

Insulin pens: the modern delivery devices.

Strict glycemic control helps in reducing complications and mortality in patients with diabetes. Insulin remains the mainstay in treatment of diabetes. One of the most important barriers to insulin therapy is the use of conventional insulin delivery system, which remains time-consuming, cumbersome, inconvenient and painful. Insulin dosing via syringe is associated with a high risk of dosage errors. The modern pen devices have various advantages over the conventional insulin delivery methods. The user-friendliness and comfort of injection makes the initiation of insulin easier. The ease of use of insulin pens and the flexibility of incorporating insulin injections into a busy lifestyle may improve diabetes control with much less effort, while maintaining the quality of life for the diabetic patients. Reusable and prefilled pens are available.

Impact of Anti-Diabetic Medications on Quality of Life in Persons with Type 2 Diabetes Mellitus.

Introduction: Type 2 diabetes mellitus (T2DM) has been found to be associated with poor quality of life (QOL). The aim of this study was to measure QOL in T2DM patients and examine if the patients' socio demographic, diabetes-related clinical characteristics and insulin usage are associated with better quality of life. Materials and Methods: This clinic based cross-sectional study analyzed data from outpatients with T2DM attending a referral clinic between January and June 2016. Association between Diabetes Attitudes, Wishes and Needs (DAWN) QOL and few demographic, socioeconomic, clinical and biochemical predictors were examined using multivariate logistic regression model. A total of 518 patients completed the interview. Results: The HbA1c level of insulin ± oral anti-diabetic (OAD) cohort was significantly lower (7.89 ± 1.98) than the OAD cohort (8.79 ± 1.96), P < 0.001. Compared to their counterparts in the OAD cohort, patients on insulin were older with longer duration of diabetes mellitus. Co-morbid confounders like obesity, hypoglycemia, and blood pressure control or socio demographic confounders like income, education were almost similar in both the cohorts. The incidence of hypertension, coronary artery disease (CAD) and statin usage was significantly higher in the insulin cohort. The overall composite DAWN QOL scores of the insulin ± OAD cohort (25.42 ± 4.35) was marginally higher than that of the OAD cohort (23.62 ± 5.06) (P = 0.067). Analog insulin users were also found to have significantly higher composite DAWN QOL scores compared to human insulin users (25.77 ± 5.73 vs.24.13 ± 4.88, P = 0.037). Conclusions: The insulin cohort, despite being older and having longer duration of diabetes, had significantly higher diet compliance score, and enhanced QOL owing to better diabetes-related knowledge and treatment adherence characteristics than non-insulin users. Questionnaires-based evaluation of QOL can provide better understanding of the patient's experience of the illness, self-care, psychological and emotional functioning, and choice of therapeutic modality enhancing the quality of care.

Metabolic and Energy Imbalance in Dysglycemia-Based Chronic Disease.

Metabolic flexibility is the ability to efficiently adapt metabolism based on nutrient availability and requirement that is essential to maintain homeostasis in times of either caloric excess or restriction and during the energy-demanding state. This regulation is orchestrated in multiple organ systems by the alliance of numerous metabolic pathways under the master control of the insulin-glucagon-sympathetic neuro-endocrine axis. This, in turn, regulates key metabolic enzymes and transcription factors, many of which interact closely with and culminate in the mitochondrial energy generation machinery. Metabolic flexibility is compromised due to the continuous mismatch between availability and intake of calorie-dense foods and reduced metabolic demand due to sedentary lifestyle and age-related metabolic slowdown. The resultant nutrient overload leads to mitochondrial trafficking of substrates manifesting as mitochondrial dysfunction characterized by ineffective substrate switching and incomplete substrate utilization. At the systemic level, the manifestation of metabolic inflexibility comprises reduced skeletal muscle glucose disposal rate, impaired suppression of hepatic gluconeogenesis and adipose tissue lipolysis manifesting as insulin resistance. This is compounded by impaired ß-cell function and progressively reduced ß-cell mass. A consequence of insulin resistance is the upregulation of the mitogen-activated protein kinase pathway leading to a pro-hypertensive, atherogenic, and thrombogenic environment. This is further aggravated by oxidative stress, advanced glycation end products, and inflammation, which potentiates the risk of micro- and macro-vascular complications. This review aims to elucidate underlying mechanisms mediating the onset of metabolic inflexibility operating at the main target organs and to understand the progression of metabolic diseases. This could potentially translate into a pharmacological tool that can manage multiple interlinked conditions of dysglycemia, hypertension, and dyslipidemia by restoring metabolic flexibility. We discuss the breadth and depth of metabolic flexibility and its impact on health and disease.

Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.

The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.

Burkholderia pseudomallei septic arthritis in Type-2 diabetes mellitus patients: Report of two cases.

Two cases of Burkholderia pseudomallei septic arthritis are presented with a brief review of the literature. B. pseudomallei septic arthritis most commonly occurs in diabetics and other immunocompromised patients and may prove fatal despite appropriate therapy. Clinical and microbiological suspicion of B. pseudomallei infection may help in providing appropriate empirical therapy.

A Practitioner's Toolkit for Insulin Motivation in Adults with Type 1 and Type 2 Diabetes Mellitus: Evidence-Based Recommendations from an International Expert Panel.

AIM: To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner's toolkit for insulin motivation in the management of diabetes mellitus (DM). BACKGROUND: Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. REVIEW RESULTS: After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. CONCLUSIONS: In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Comparative Efficacy and Safety Among Sodium-glucose Cotransporter-2 Inhibitors in Type 2 Diabetes - Results from a Retrospective Single-centre Study.

Introduction: This retrospective analysis compared the real-world effectiveness and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus in India. Methods: All patients initiated on canagliflozin (C; 100 mg), dapagliflozin (D; 10 mg) and empagliflozin (E; 10 mg) between January and December 2016 were identified from an urban outpatient facility. Intra- and inter-group changes in glycaemic and metabolic parameters were recorded. Results: At week 48 (median follow-up), mean changes from baseline in the C (n=29), D (n=65) and E groups (n=27), respectively, were -1.3% (p=0.0002), -0.9% (p<0.0001) and -0.7% (p=0.34) for glycated haemoglobin; -60.9 mg/dL (p=0.00), -50.2 mg/dL (p=0.00) and -46.7 mg/dL (p=0.01) for fasting plasma glucose; -100.6 mg/dL (p=0.00), -79.8 mg/dL (p=0.00) and -90.2 mg/dL (p=0.00) for postprandial plasma glucose; -1.7 kg (p<0.05), -2.1 kg (p=0.0004) and -3.7 kg (p=0.002) for body weight; -5.2 mmHg (p=0.10), -5.8 mmHg (p=0.009); 0.0 mmHg (p=0.80) for systolic blood pressure and -12.2% (p=0.26), -9.2% (p=0.27) and -9.7% (p=0.50) for proportion of patients taking insulin. The incidence rate of hypoglycaemia was 2.4% for C, 1.3% for D, and 6.4% for E group. No significant inter-group differences were noted. Conclusion: Overall intra-group changes in glycaemic and metabolic parameters were significant; however, inter-group changes among SGLT2i were not significant, thereby indicating a class effect of the efficacy and safety parameters.