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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia.

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The prevalence of obesity is rapidly increasing worldwide. One-thirds of world population is suffering from the deleterious effects of excessive fat and adipose tissue in their body. At the same time, the average life expectancy is becoming higher and higher every decade. Therefore, living healthy and longer is the dream for everyone. Simply being obese is not the primary cause for the consequence of obesity; rather, the depot where the fat is accumulated, is the primary key for the deleterious effects of obesity. Results from historical research suggest that visceral fat increases the risk for cardiovascular and metabolic diseases, such as diabetes, myocardial infarction and ischemic stroke, not subcutaneous fat. Therefore, body mass index (BMI), which reflects body weight relative to height might not reflect the appropriate size of metabolic burden of fat in our body. In contrast, waist circumference, which reflects abdominal obesity, would mirror the metabolic burden of fat better than BMI. Visceral fat is the marker of ectopic fat accumulation. In this review, I will introduce my researches mainly involved in uncovering the clues to the link between metabolic health and cardiovascular disease.

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The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.

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As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.

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The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

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The Korean Diabetes Association (KDA) recently updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not changed from those of the 2015 KDA guidelines. The Committee on Clinical Practice Guidelines of the KDA has extensively reviewed and discussed the results of meta-analyses and systematic reviews of effectiveness and safety of OHAs and many clinical trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient's clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity. In this review, we address the results of meta-analyses and systematic reviews, comparing the effectiveness and safety among OHAs. It will help to choose the appropriate drug for an individual patient with T2DM.

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Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis.

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In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.

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In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.

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Green tea or green tea extract (GT/GTE) has been demonstrated to reduce insulin resistance and improve glycemic control. However, evidence for this health beneficial effect is inconsistent. This systematic review evaluated the effect of GT/GTE on insulin resistance and glycemic control in people with pre-diabetes/type 2 diabetes mellitus (T2DM). Ovid MEDLINE, Embase, AMED, Web of Science, and the Cochrane Library were searched up to April 2017 for randomised controlled trials of participants with pre-diabetes or T2DM, where the intervention was GT/GTE. Meta-analysis was performed to assess the standardised mean difference (SMD) in biomarkers of insulin resistance and glycemic control between GT/GTE and placebo groups. Six studies (n=382) were pooled into random-effects meta-analysis. Overall, no differences were found between GT/GTE and the placebo for glycosylated hemoglobin (HbA1c: SMD, −0.32; 95% confidence interval [CI], −0.86 to 0.23), homeostatic model assessment for insulin resistance (HOMA-IR: SMD, 0.10; 95% CI, −0.17 to 0.38), fasting insulin (SMD, −0.25; 95% CI, −0.64 to 0.15), and fasting glucose (SMD, −0.10; 95% CI, −0.50 to 0.30). No evidence support the consumption of GT/GTE could reduce the levels of HbA1c, HOMA-IR, fasting insulin, or fasting glucose in people with pre-diabetes/T2DM. However, the studies included were small and of varying quality.

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The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity.

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The Hospital Authority of Hong Kong is a statutory body that manages all the public medical care institutions in Hong Kong. There are currently around 400,000 diabetic patients under its care at 17 hospitals (providing secondary care for 40%) and 73 General Outpatient Clinics (providing primary care for 60%). The patient population has been growing at 6% to 8% per year over the past 5 years, estimated to include over 95% of all diagnosed patients in Hong Kong. In order to provide equitable and a minimal level of care within resources and local system factors constraints, a Clinical Practice Guideline on the management of type 2 diabetes mellitus was drawn in 2013 to guide a system approach to providing diabetes care. There is an algorithm for the use of various hypoglycemic agents. An organizational drug formulary governs that less expansive options have to be used first. A number of clinical care and patient empowerment programs have been set up to support structured and systematic diabetes care. With such a system approach, there have been overall improvements in diabetes care with the percentage of patients with glycosylated hemoglobin <7% rising from 40% in 2010 to 52% in 2015.

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Chronic endoplasmic reticulum (ER) stress culminating in proteotoxicity contributes to the development of insulin resistance and progression to type 2 diabetes mellitus. Pharmacologic interventions targeting several different nuclear receptors have emerged as potential treatments for insulin resistance. The mechanistic basis for these antidiabetic effects has primarily been attributed to multiple metabolic and inflammatory functions. Here we review recent advances in our understanding of the association of ER stress with insulin resistance and the role of nuclear receptors in promoting ER stress resolution and improving insulin resistance in the liver.

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Clinical trials have demonstrated the efficacy of lifestyle modification for the prevention of type 2 diabetes mellitus but it was achieved at higher cost than can be sustained in routine health services. The first clinical trial to report was the Finnish Diabetes Prevention Study. This paper describes how Australia worked with Finnish colleagues to adapt the findings of that study to achieve a statewide diabetes prevention program. Small evaluative, effectiveness trials have been conducted in a number of countries to see if the results of the clinical trials can be replicated in routine health services. The Australian evaluative trial, Greater Green Triangle Diabetes Prevention Program is described in detail to demonstrate the ingredients for success in moving a program from one country to another. Few countries have managed to scale up from evaluative trials to statewide or national programs. The Australian experience is described in detail including lessons learned about what reduced the effectiveness, particularly the need for policy makers in government, people from the implementing organisation and researchers to work together from the start of the evaluative trial and throughout the first 5 years of a national program.

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