Barriers to the Use of Insulin Therapy and Potential Solutions: A Narrative Review of Perspectives from the Asia-Pacific Region.

The rising prevalence of type 2 diabetes (T2D) is posing major challenges for the healthcare systems of many countries, particularly in the Asia-Pacific Region, in which T2D can present at younger ages and lower body mass index when compared with Western nations. There is an important role for insulin therapy in the management of T2D in these nations, but available evidence suggests that insulin is under-utilized and often delayed, to the detriment of patient prognosis. The authors of this article gathered as an advisory panel (representative of some of the larger Asia-Pacific nations) to identify their local barriers to insulin use in T2D, and to discuss ways in which to address these barriers, with their outputs summarized herein. Many of the key barriers identified are well-documented issues of global significance, including a lack of healthcare resources or of an integrated structure, insufficient patient education, and patient misconceptions about insulin therapy. Barriers identified as more innate to Asian countries included local inabilities of patients to afford or gain access to insulin therapy, a tendency for some patients to be more influenced by social media and local traditions than by the medical profession, and a willingness to switch care providers and seek alternative therapies. Strategies to address some of these barriers are provided, with hypothetical illustrative case histories.

Rare and aggressive metastatic pheochromocytoma recurrence in a patient with MEN 2A syndrome.

An adult male in his early 30s diagnosed with multiple endocrine neoplasia type 2A syndrome, confirmed through genetic testing, presented as bilateral pheochromocytoma in a metachronous fashion, primary hyperparathyroidism and medullary thyroid carcinoma. Left and right adrenalectomy was done 9 years and 3 years ago, respectively. He was also subjected to total thyroidectomy with neck dissection and left inferior parathyroidectomy. During surveillance monitoring, 24-hour total urine metanephrines were elevated 13.977 mg (Normal value 0-1 mg) 1 year after right adrenalectomy. Adrenal CT scan demonstrated a 2.1 cm ovoid focus in the right suprarenal region, and functional imaging (131I meta-iodobenzylguanidine (MIBG scan) showed an avid uptake on the right frontal bone. Excision of the right adrenal bed and the right frontal bone tumour was performed, and metastatic pheochromocytoma was confirmed histologically. The patient achieved clinical and biochemical remission postoperatively and is currently receiving steroid and thyroxine replacement.

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.

Targeting the Filipino gut microbiota in the management of hypertension.

BACKGROUND: Hypertension is a major health problem in the Philippines, being the second leading disease and the second leading factor driving the most death and disability in the country. Despite efforts made toward increasing awareness, improving availability of medications, and strengthening patient adherence, more than 7 in every 10 hypertensive Filipinos still have uncontrolled hypertension. MAIN BODY: In the recent years, the role of gut microbiota in hypertension has been highlighted, with studies showing alterations in the gut microbiota of hypertensive individuals and its positive effect on the pharmacokinetics of some antihypertensive drugs. CONCLUSIONS: These findings show how gut microbiota can be an important but possibly overlooked consideration in the management of hypertension in the Philippines. Clinicians might benefit from maximizing the relationship between gut microbiota and hypertension to achieve good BP control and ultimately address the burden of uncontrolled hypertension in the country.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries.

INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. METHODS: This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal-bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. RESULTS: Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26-36; estimated change - 1.4% [95% CI - 1.51; - 1.29]; P < 0.0001 [primary outcome]). From baseline to EOS, there were significant reductions in fasting plasma glucose (- 2.7 mmol/L [95% CI - 2.98; - 2.46]; P < 0.0001), body weight (- 1.0 kg [95% CI - 1.51; - 0.52]; P < 0.0001), and basal insulin dose in insulin-experienced participants (- 2.3 units [95% CI - 3.51; - 1.01]; P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. CONCLUSION: In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. TRIAL REGISTRATION: Clinical trial registration NCT04042441.

ARISE-a prospective, non-interventional, single-arm study assessing clinical parameters associated with the use of insulin degludec/insulin aspart in patients with type 2 diabetes in real-world settings: rationale and design.

PURPOSE: IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. METHODS: ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of <7% at the study end, respectively. A mixed model for repeated measurements will analyse the primary endpoint. CONCLUSION: Between-country differences in the prescription patterns of glucose-lowering agents in people with T2D warrant examination of their clinical use in different geographical settings. The ARISE study is designed to assess the clinical use of IDegAsp from real world in six different countries. Findings from the ARISE study will supplement those of previous randomised controlled studies by establishing real-world evidence of IDegAsp use in the participating countries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04042441. Registered 02 August 2014, https://clinicaltrials.gov/ct2/show/NCT04042441.

Biochemistry and molecular biology in health science education: A parallel session at the IUBMB/PSBMB 2019 "Harnessing Interdisciplinary Education in Biochemistry and Molecular Biology" conference.

In many health-related programs biochemistry and molecular biology are core subjects, but these subjects are often not the students main focus. This challenges educators to develop curriculum that demonstrates the relevance of biochemistry and molecular biology and engages these students. This conference session discussed the value of biochemistry and molecular biology education in the health sciences and the methodologies which can be implemented.

Management of Type 2 Diabetes in Developing Countries: Balancing Optimal Glycaemic Control and Outcomes with Affordability and Accessibility to Treatment.

With the growing prevalence of type 2 diabetes, particularly in emerging countries, its management in the context of available resources should be considered. International guidelines, while comprehensive and scientifically valid, may not be appropriate for regions such as Asia, Latin America or Africa, where epidemiology, patient phenotypes, cultural conditions and socioeconomic status are different from America and Europe. Although glycaemic control and reduction of micro- and macrovascular outcomes remain essential aspects of treatment, access and cost are major limiting factors; therefore, a pragmatic approach is required in restricted-resource settings. Newer agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in particular, are relatively expensive, with limited availability despite potentially being valuable for patients with insulin resistance and cardiovascular complications. This review makes a case for the role of more accessible second-line treatments with long-established efficacy and affordability, such as sulfonylureas, in the management of type 2 diabetes, particularly in developing or restricted-resource countries.

Prevention of Excessive Gestational Weight Gain and Postpartum Weight Retention.

PURPOSE OF REVIEW: The purpose of this review is to summarize the current evidence on the prevention of excessive gestational weight gain (GWG) and reduction of postpartum weight retention (PPWR) by lifestyle intervention and pharmacotherapy. RECENT FINDINGS: Recent findings demonstrate that tailored nutrition counseling and adapting certain eating patterns, supervised exercise programs aiming at achieving at least moderate level of physical activity, and interactive and monitored behavior change interventions are effective in reducing excessive GWG and PPWR. Among the pharmacologic agents, Metformin has been shown to reduce GWG. Excessive GWG and PPWR are associated with adverse maternal and neonatal outcomes. Recent evidence shows that weight during gestation and the postpartum period can be significantly reduced by more frequent nutrition counseling sessions on balanced diet focusing on healthier food choices and eating patterns, supervised moderate-intensity exercise for at least 30 min three times a week, and interactive behavior change interventions with regular feedback and follow-up. The benefits on weight are seen when these interventions are utilized together in a multimodality approach. Metformin is effective in preventing excessive GWG but has no impact on neonatal outcomes.

Self-Reported Hypoglycemia in Insulin-Treated Patients with Diabetes: Results from the Philippine Cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) Study.

OBJECTIVE: To determine the frequency of hypoglycemia in insulin-treated patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study. METHODOLOGY: This sub-analysis included Filipino patients with T1DM or T2DM, aged 18 years and older, treated with insulin for more than 12 months, who completed the two-part self-assessment questionnaires (SAQ1 and SAQ2) and patient diaries that recorded hypoglycemia during retrospective (6 months/4 weeks before baseline) and prospective period (4 weeks after baseline) (ClinicalTrials.gov number: NCT02306681). RESULTS: A total of 671 patients were enrolled and completed the SAQ1 (62 patients with T1DM and 609 patients with T2DM). Almost all patients (100% in T1DM and 99.3% in T2DM) experienced at least 1 hypoglycemic event prospectively. The incidence of any hypoglycemia was also high in the prospective period compared to retrospective period (72.6 [95% CI: 64.8, 80.9] events PPY and 43.6 [95% CI: 37.8, 49.9] events PPY; p=0.001, respectively) in T1DM patients. CONCLUSION: Among insulin-treated patients, higher rates of hypoglycemia were reported prospectively than retrospectively. This indicates that the patients in real-life setting often under-report hypoglycemia. Patient education can help in accurate reporting and appropriate management of hypoglycemia and diabetes.

Hypoglycaemia among Insulin-Treated Patients with Diabetes: Southeast Asia Cohort of IO HAT Study.

OBJECTIVE: To provide real-world data on hypoglycaemia incidence in patients with type 1 (T1D) or type 2 diabetes (T2D) from the Southeast Asian cohort of the International Operations Hypoglycaemia Assessment Tool (IO HAT) study. METHODOLOGY: IO HAT was a non-interventional, multicentre, 6-month retrospective and 4-week prospective study of hypoglycaemic events among insulin-treated adults with T1D or T2D, including four countries in Southeast Asia (Singapore, Philippines, Indonesia, and Bangladesh). Data were collected using a two-part self-assessment questionnaire (SAQ1 for retrospective and SAQ2 for prospective). The primary endpoint was the percentage of patients experiencing at least one hypoglycaemic event during the 4-week prospective observational period (ClinicalTrials.gov Identifier: NCT02306681). RESULTS: A total of 2594 patients completed SAQ1. Nearly all patients reported experiencing any hypoglycaemic event in the 4-week prospective period (T1D, 100%; T2D, 97.3%), with all patients reporting higher rates in the prospective versus retrospective period. Severe hypoglycaemia was also reported higher prospectively (57.2% and 76.9%) than retrospectively (33.9% and 12.2%) in both T1D and T2D, respectively. Nocturnal hypoglycaemia was reported higher retrospectively than prospectively. CONCLUSION: Incidence of any and severe hypoglycaemia in the Southeast Asian cohort of IO HAT was higher prospectively versus retrospectively, suggesting hypoglycaemia has previously been under-reported in this region.

Development and Validation of a Questionnaire Evaluating Impaired Hypoglycemia Awareness among Adult Filipino Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Hazards of hypoglycemia include accidents, cardiovascular events, neurologic damage, and impaired hypoglycemia awareness (IHA) which presents as inability to perceive and respond to hypoglycemic warning symptoms. OBJECTIVE: This study aimed to develop the first questionnaire evaluating IHA adapted from Clarke Hypoglycemia Index (CHI) and validated among adult Filipino patients with Type 2 Diabetes Mellitus (T2DM). METHODOLOGY: A questionnaire development study was conducted involving CHI linguistic translation, its modification through literature review and focus group discussions, panel synthesis, and content validity. A cross-sectional analytic study followed by administration of the questionnaire to 117 adult Filipinos with T2DM, advanced age, long-standing T2DM, insulin or sulfonylurea, polypharmacy, comorbidities and/or prior hypoglycemia. There were 9 participants in pilot testing, 69 in criterion validity against continuous glucose monitoring (CGM), and 108 in construct validity. RESULTS: IHA domains in the concept map included Elusive Euglycemia Model, Developmental Model, and Cognitive Model. The Filipino-CHI formulated had 8 questions with content validity scores ranging from 87.5-93.75%. Owing to brevity, its internal consistency Cronbach's alpha was 0.45. Criterion validity against CGM yielded 21 patients with biochemical hypoglycemic events, of which 2 had clinical hypoglycemic events and 19 were positive monitor-identified IHA. A questionnaire IHA cutoff score of ≥4 had sensitivity of 89.47%, and area under the curve of 0.55. CONCLUSION: An 8-item questionnaire evaluating IHA among adult Filipino T2DM patients was developed and validated.

Self-monitoring of blood glucose as part of a multi-component therapy among non-insulin requiring type 2 diabetes patients: a meta-analysis (1966-2004).

OBJECTIVE: To determine if therapeutic management programs that include self-monitoring of blood glucose result in greater HbA1c reduction in non-insulin-requiring type 2 diabetes patients compared to programs without blood glucose self-monitoring. RESEARCH DESIGN AND METHODS: Electronic databases including MEDLINE (1966-2004), Cochrane Database of Systematic Reviews, EMBASE (1950-2004), Centre for Reviews and Dissemination (CRD) and the Online Index Journals of the American Diabetes Association (ADA 1978-2004) were searched. Personal collections of investigators were also explored. Randomized controlled trials comparing HbA1c reduction in therapies with and without blood glucose self-monitoring among adult, non-insulin-treated type 2 diabetes patients were selected. Studies on patients who are pregnant, taking insulin, troglitazone or experimental drugs were excluded. Out of 14 potentially useful randomized controlled trials on self-monitoring of blood glucose in non-insulin treated type 2 diabetes patients, eight studies with a total of 1307 subjects were included in the analysis. Two independent reviewers assessed the quality of studies. MAIN OUTCOME MEASURE: The effect of SMBG was assessed by means of meta-analysis of the difference in HbA1c reduction between self-monitoring and non-self-monitoring groups. RESULTS: Antidiabetic therapies that included blood glucose self-monitoring as part of a multi-component management strategy produced a mean additional HbA(1c) reduction of -0.39% (95%CI: -0.54%, -0.23%) under the fixed effects model and -0.42% (95%CI: -0.63%, -0.21%) under the random effects model, when compared to therapies that did not. Heterogeneity among studies was not statistically significant. CONCLUSION: Multi-component diabetes management programs with self-monitoring of blood glucose result in better glycemic control among non-insulin-using type 2 diabetes patients.