ACTION APAC: Understanding perceptions, attitudes and behaviours in obesity and its management across south and Southeast Asia.

To identify perceptions and attitudes among people with obesity (PwO) and healthcare professionals (HCPs) toward obesity and its management in nine Asia-Pacific (APAC) countries, a cross-sectional online survey was conducted among adult PwO with self-reported body mass index of ≥25 kg/m2 (≥27 kg/m2, Singapore), and HCPs involved in direct patient care. In total, 10 429 PwO and 1901 HCPs completed the survey. Most PwO (68%) and HCPs (84%) agreed that obesity is a disease; however, a significant proportion of PwO (63%) and HCPs (41%) believed weight loss was the complete responsibility of PwO and only 43% of PwO discussed weight with an HCP in the prior 5 years. Most respondents acknowledged that weight loss would be extremely beneficial to PwO's overall health (PwO 76%, HCPs 85%), although nearly half (45%) of PwO misperceived themselves as overweight or of normal weight. Obesity was perceived by PwO (58%) and HCPs (53%) to negatively impact PwO forming romantic relationships. HCPs cited PwOs' lack of interest (41%) and poor motivation (37%) to lose weight as top reasons for not discussing weight. Most PwO (65%) preferred lifestyle changes over medications to lose weight. PwO and HCPs agreed that lack of exercise and unhealthy eating habits were the major barriers to weight loss. Our data highlights a discordance between the understanding of obesity as a disease and the actual behaviour and preferred approaches to manage it among PwO and HCPs. The study addresses a need to align these gaps to deliver optimal care for PwO.

Impact of My Dose Coach App Frequency of Use on Clinical Outcomes in Type 2 Diabetes.

INTRODUCTION: My Dose Coach (MDC) is a US Food and Drug Administration-approved digital smartphone application designed to help users with type 2 diabetes (T2D) titrate their basal insulin (BI) according to a clinician-prescribed individualized titration plan. The aim of this analysis was to assess the impact of the frequency of MDC use on clinical outcomes. METHODS: This retrospective observational analysis included people with T2D who were registered for MDC (August 1st, 2018-April 30th, 2020) and received BI. Users with an activated care plan and ≥2 fasting blood glucose (FBG) observations spanning ≥2 weeks were defined as active. Outcomes included percentage achieving their individual FBG target, time to FBG target, change in FBG, change in insulin dose and hypoglycemia. Users were stratified into high (>3 days per week), moderate (>1- ≤3 days per week), and low (≤1 day per week) MDC usage groups. RESULTS: The analysis included 2517 active MDC users. Approximately 49% of users had high MDC usage. Overall, 44% of users across all usage frequencies achieved their individual FBG target. High MDC use was associated with significantly better FBG target achievement and less time to FBG target versus moderate- and low-usage groups (p≤0.01 for all). Insulin dose change was significantly greater in the high- versus moderate-usage group (p=0.01). There was no significant difference in hypoglycemia incidence among MDC usage groups (12%-16% of users in any usage group). CONCLUSIONS: More frequent MDC usage was associated with better FBG outcomes without increased hypoglycemia risk.

Postprandial Glucose Excursions in Asian Versus Non-Asian Patients with Type 2 Diabetes: A Post Hoc Analysis of Baseline Data from Phase 3 Randomised Controlled Trials of IDegAsp.

INTRODUCTION: Increased postprandial glucose (PPG) is associated with high glycated haemoglobin levels and is an independent risk factor for cardiovascular diseases. The aim of this study was to compare PPG increments in Asian versus non-Asian adults with type 2 diabetes (T2D), who were insulin-naïve or insulin-experienced, from the phase 3 insulin degludec/insulin aspart (IDegAsp) clinical trials. METHODS: This was a post hoc analysis of data from 13 phase 3, randomised, parallel-group, open-label IDegAsp trials in patients with T2D. The pooled baseline clinical data were analysed for insulin-naïve and insulin-experienced groups; and each group was split into subgroups of Asian and non-Asian patients, respectively, and analysed accordingly. Baseline self-monitored blood glucose (SMBG) values at breakfast, lunch and the evening meal (before and 90 min after each meal) were used to assess PPG increments. The estimated differences in baseline SMBG increment between the Asian and non-Asian subgroups were analysed. RESULTS: Clinical data from 4750 participants (insulin-naïve, n = 1495; insulin-experienced, n = 3255) were evaluated. In the insulin-naïve group, the postprandial SMBG increment was significantly greater in the Asian versus the non-Asian subgroup at breakfast (estimated difference 28.67 mg/dL, 95% confidence interval [CI] 18.35, 38.99; p < 0.0001), lunch (17.34 mg/dL, 95% CI 6.47, 28.21; p = 0.0018) and the evening meal (16.19 mg/dL, 95% CI 5.04, 27.34; p = 0.0045). In the insulin-experienced group, the postprandial SMBG increment was significantly greater in the Asian versus non-Asian subgroup at breakfast (estimated difference 13.81 mg/dL, 95% CI 9.19, 18.44; p < 0.0001) and lunch (29.18 mg/dL, 95% CI 24.22, 34.14; p < 0.0001), but not significantly different at the evening meal. CONCLUSION: In this post hoc analysis, baseline PPG increments were significantly greater in Asian participants with T2D than in their non-Asian counterparts at all mealtimes, with the exception of the evening meal in insulin-experienced participants. Asian adults with T2D may benefit from the use of regimens that control PPG excursions. CLINICAL TRIAL NUMBERS: NCT02762578, NCT01814137, NCT01513590, NCT01009580, NCT01713530, NCT02648217, NCT01045447, NCT01365507, NCT01045707, NCT01272193, NCT01059812, NCT01680341, NCT02906917.

Management of diabetes mellitus through teleconsultation during COVID-19 and similar scenarios - Guidelines from Indian Council of Medical Research (ICMR) expert group.

INTRODUCTION: Emergence of COVID-19 pandemic has led to increased use of telemedicine in health care delivery. Telemedicine facilitates long-term clinical care for monitoring and prevention of complications of diabetes mellitus. GUIDELINES: Precise indications for teleconsultation, clinical care services which can be provided, and good clinical practices to be followed during teleconsultation are explained. Guidance on risk assessment and health education for diabetes risk factors, counselling for blood glucose monitoring, treatment compliance, and prevention of complications are described. CONCLUSION: The guidelines will help physicians in adopting teleconsultation for management of diabetes mellitus, facilitate access to diabetes care and improve health outcomes.

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.

Fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes reported from tropical countries, associated with both endocrine and exocrine disease of the pancreas. The pre-diabetic phase of the disease is called tropical chronic pancreatitis (TCP). Currently FCPD is classified as a secondary form of diabetes called pancreatic diabetes, because essentially the disease is caused by pancreatic damage. There is an overlap of these subjects with idiopathic, non-alcoholic pancreatitis. This review will cover the etiopathogenesis, diagnosis and management of this clinical condition. FCPD could lead to endocrine dysfunction (diabetes and its complications) as well as exocrine dysfunction, and is associated with a higher risk of pancreatic cancer, for which early detection is important.

New Concepts in the Management of Charcot Neuroarthropathy in Diabetes.

Charcot Neuroarthropathy (CN) is an uncommon, debilitating and often underdiagnosed complication of chronic diabetes mellitus though, it can also occur in other medical conditions resulting from nerve injury. Till date, the etiology of CN remains unknown, but enhanced osteoclastogenesis is believed to play a central role in the pathogenesis of CN, in the presence of neuropathy. CN compromises the overall health and quality of life. Delayed diagnosis can result in a severe deformity that can act as a gateway to ulceration, infection and in the worst case, can lead to limb loss. In an early stage of CN, immobilization with offloading plays a key role to a successful treatment. Medical therapies seem to have limited role in the treatment of CN.In case of severe deformity, proper footwear or bracing may help prevent further deterioration and development of an ulcer. In individuals with a concomitant ulcer with osteomyelitis, soft tissue infection and severe deformity, where conservative measures fall short, surgical intervention becomes the only choice of treatment. Early diagnosis and proper management at an early stage can help prevent the occurrence of CN and amputation.

Barophenotypic Characterization - The key to Person Centric Management of Obesity.

Obesity is now recognized as a chronic disease by many international medical societies. However, its comprehensive assessment is still a challenge in most clinical settings. This paper describes a novel practical approach to assess the barophenotype of a given individual. The word barophenotype is a portmanteau of "baro," which means weight, and phenotype, which reflects an external expression of a trait. This can be easily assessed using an ABCDE framework, encompassing the Adipose topography, Barophenotypic Behavior, Comorbidity assessment, Dysfunctionality, and Expectations. Furthermore, the utility of this framework in determining an appropriate person-centric therapeutic plan has also been described.

Cardiorenal Syndrome in Type 2 Diabetes Mellitus - Rational Use of Sodium-glucose Cotransporter-2 Inhibitors.

Cardiorenal syndrome (CRS) in people with type 2 diabetes mellitus (T2DM) illustrates the bidirectional link between the heart and the kidneys, with acute or chronic dysfunction of one organ adversely impacting the function of the other. Of the five subtypes identified, type 1 and 2 CRS occur because of the adverse impact of cardiac conditions on the kidneys. Type 3 and 4 occur when renal conditions affect the heart, and in type 5, systemic conditions impact the heart and kidneys concurrently. The cardiovascular and renoprotective benefits evidenced with sodium-glucose cotransporter-2 (SGLT2) inhibitors make them a potential choice in the management of CRS. Cardiovascular protection is mediated by a reduction in cardiac workload, blood pressure, and body weight; with improvement in lipid profile, uric acid levels, and adaptive ketogenesis process. Renoprotection is facilitated by reduction in albuminuria and hypoxic stress, and restoration of tubuloglomerular feedback. The favourable effect on cardiovascular complications and death, as well as renal complications and progression to end-stage kidney disease, has been confirmed in clinical trials. Guidelines endorse first-line use of SGLT2 inhibitors after metformin in patients with T2DM with high cardiovascular risk, chronic kidney disease or both. Since most trials with SGLT2 inhibitors excluded subjects with acute illness, patients with CRS subtypes 1 and 3 have not been studied adequately, making SGLT2 initiation in clinical practice challenging. Ongoing trials may provide evidence for SGLT2 inhibitor use in CRS. This review aims to enhance understanding of CRS and provide guidance for judicious use of SGLT2 inhibitors in T2DM.

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.

Effect of a Low-Calorie Diet on Restoration of Normoglycemia in Obese subjects with Type 2 Diabetes.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. METHODS: We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. RESULTS: This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C-Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. CONCLUSION: If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease.

The Effect of Yoga and Peer Support Interventions on the Quality of Life of Women with Diabetes: Results of a Randomized Controlled Trial.

OBJECTIVE: This was an interventional study to understand the effect of two low-cost interventions; yoga and peer support on the quality of life (QOL) of women with type 2 diabetes. METHODOLOGY: An open label parallel three-armed randomized control trial was conducted among 124 recruited women with diabetes for 3 months. Block randomization with a block length of six was carried out. In the yoga arm, sessions by an instructor, consisting of a group of postures coordinated with breathing were conducted for an hour, 2 days a week. In the peer support arm, each peer mentor after training visited 13-14 women with diabetes every week followed by a phone call. The meeting was about applying disease management plans in daily life. At the beginning and end of the study, QOL was assessed by the translated, validated World Health Organization QOL-BREF in four domains physical, psychological, social, and environmental domains. RESULTS: The majority (96%) of the study participants perceived the peer support and yoga intervention to be beneficial. Paired t-test revealed significant increases in the social and environmental domain in the peer group and in the environmental domain in the yoga group, though this disappeared in the between-group comparison perhaps due to poor glycemic control (hemoglobin A1c varied from 9.4 to 9.6) and the short duration of 3 months of the study. CONCLUSION: Peer support and yoga improved perceptions of QOL though its impact on scores was not significant due to a short period of study among women with poor glycemic 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.

Flexibility in insulin prescription.

This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

Glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes: Past, present, and future.

Glucagon-like peptide-1 (GLP-1)-based therapy improves glycaemic control through multiple mechanisms, with a low risk of hypoglycaemia and the additional benefit of clinically relevant weight loss. Since Starling and Bayliss first proposed the existence of intestinal secretions that stimulate the pancreas, tremendous progress has been made in the area of incretins. As a number of GLP-1 receptor agonists (GLP-1 RAs) continue to become available, physicians will soon face the challenge of selecting the right option customized to their patient's needs. The following discussion, derived from an extensive literature search using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide, provides a comprehensive review of existing and upcoming molecules in the GLP-1 RA class in terms of their structure, pharmacological profiles, efficacy, safety, and convenience. Search Methodology: A literature search was conducted using the PubMed database, applying the terms incretin, GLP-1, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, semaglutide, and taspoglutide. Relevant articles were those that discussed structural, pharmacokinetic and pharmacodynamic differences, classification, long-acting and short-acting GLP-1 RAs, phase 3 trials, and expert opinions. Additional targeted searches were conducted on diabetes treatment guidelines and reviews on safety, as well as the American Diabetes Association/European Society for Study of Diabetes (ADA/EASD) statement on pancreatic safety.

Self-Treated Hypoglycemia in Type 2 Diabetes Mellitus: Results from the Second Wave of an International Cross-Sectional Survey.

INTRODUCTION: The aim of this study was to assess the total frequency of self-treated hypoglycemia in type 2 diabetes mellitus patients using regimens including basal insulin analogs, and to describe the psychological impact and behavioral response to these events from the perspective of patients and prescribers (i.e., hospital specialists and primary care physicians). METHODS: The global attitude of patients and physicians 2 (GAPP2) survey was an online multinational, cross-sectional survey of patients with type 2 diabetes mellitus treated with basal insulin analogs, with or without bolus insulin. Prescribers directly involved in the care of these patients were also surveyed. Here, we report the results of the second wave of the GAPP2 survey, in which the primary variable of interest was self-treated hypoglycemia. RESULTS: A total of 855 patients and 1003 prescribers, from 7 countries, completed the survey. Overall, 28% of patients had experienced self-treated hypoglycemia during the previous 30 days, with two-thirds of events occurring during the day and one-third of events occurring nocturnally. Prescribers reported discussing events with 55% of patients over this period. Patients worried about self-treated hypoglycemia in a range of situations, and prescribers under-estimated this worry. Many patients who had experienced self-treated hypoglycemia in the last 30 days reported missing (19%), mistiming (7%), or reducing (7%) their basal insulin dose as a result. CONCLUSION: Self-treated hypoglycemia was relatively common in patients using basal insulin analogs, with or without bolus insulin. Whilst the frequency of hypoglycemia was greater during the daytime than at night, patients worried more about nocturnal events and this level of worry was under-estimated by physicians. Additional advice and support may be needed for both patients and prescribers, to reduce the frequency and impact of self-treated hypoglycemia. FUNDING: Novo Nordisk.