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The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM., Competing Interests: The development of these expert recommendations was supported by an unrestricted educational grant from AstraZeneca Ltd, who had no influence on the content. All authors have read, approved, and take full responsibility for the accuracy of the content., (Copyright © 2020 Korean Diabetes Association.)

Aim: To evaluate the safety of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), and its effects on body weight management in adults without diabetes., Materials and Methods: In this phase II, randomized, placebo-controlled, double-blind trial, participants with a body mass index (BMI) ≥30 kg/m 2 or ≥27 kg/m 2 with comorbidity were randomized 1:1:1:1:1 to efpeglenatide (4 mg once weekly, 6 mg once weekly, 6 mg once every 2 wk, or 8 mg once every 2 wk; n = 237) or placebo (n = 60) in combination with a hypocaloric diet. The primary endpoint was body weight change from baseline after 20 wk of treatment, assessed using a mixed-effect model with repeated measures with an unstructured covariance matrix over all post-screening visits; treatment comparisons were based on least squares mean estimates., Results: Over 20 wk, all doses of efpeglenatide significantly reduced body weight from baseline versus placebo (P < 0.0001), with placebo-adjusted reductions ranging between -6.3 kg (6 mg once every 2 wk) and -7.2 kg (6 mg once weekly). Greater proportions of efpeglenatide-treated participants had body weight loss of ≥5% or ≥10% versus placebo (P < 0.01, all comparisons). Efpeglenatide led to significant improvements in glycaemic variables (fasting plasma glucose and glycated haemoglobin) and lipid profiles (cholesterol, triglycerides) versus placebo. Rates of study discontinuations as a result of adverse events ranged from 5% to 19% with efpeglenatide. Gastrointestinal effects were the most common treatment-emergent adverse events., Conclusions: Efpeglenatide once weekly and once every 2 wk led to significant body weight reduction and improved glycaemic and lipid variables versus placebo. It was also well tolerated for weight management in adults without diabetes., (© 2019 John Wiley & Sons Ltd.)

Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses., (© 2016 by the American Diabetes Association.)

BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25 kg/m(2). People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.

Background: Recent studies have suggested a possible association between outdoor or indoor temperature and obesity. We aimed to examine whether ambient temperature is associated with the prevalence of obesity or abdominal obesity in the Korean population., Methods: Data on anthropometric, socio-demographic, laboratory and lifestyle factors were retrieved from National Health Insurance System data obtained in 2009-2010. Thirty years (1981 to 2010) of meteorological parameters for 71 observation areas were acquired from the Korea Meteorological Administration. Included in this analysis were 124,354 individuals. A body mass index (BMI) ≥ 25 kg/m2 and a waist circumference (WC) ≥ 90 cm (men) or 85 cm (women) were considered to represent obesity and abdominal obesity, respectively., Results: The mean annual temperature (MAT) ranged from 6.6°C to 16.6°C, and BMI was positively correlated with MAT (r = 0.0078, P = 0.0065). WC was positively correlated with MAT (r = 0.0165, P < 0.0001) and negatively correlated with the number of days with mean temperature < 0°C (DMT0; r = -0.0129, P = 0.0002). After adjusting for age, sex, smoking status, alcohol consumption, exercise, income, residential area and altitude, the odds ratios (95% CI) for obesity and abdominal obesity in the highest quintile MAT group were 1.045 (1.010, 1.081) and 1.082 (1.042, 1.124), respectively, compared with the lower four quintiles of the MAT group. Similarly, subjects in the area of the lowest quintile of DMT0 had significantly higher odds of abdominal obesity compared with the higher four quintile groups of DMT0., Conclusion: This study finds an association between ambient temperature and prevalence of obesity in the Korean population when controlling for several confounding factors. Adaptive thermogenesis might be a possible explanation for this phenomenon.

Metabolic health and obesity are not stable conditions, and changes in the status of these conditions might lead to different clinical outcomes. We aimed to determine whether changes in metabolic health status or obesity over time have any effect on the risk of future diabetes. Nondiabetic individuals (n = 2692) from a population-based prospective cohort study with baseline and 2 follow-up examinations at 4-year intervals were included. Being "metabolically obese" (MO) was defined as being in the highest quartile of the TyG index (ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]), whereas falling into the lower 3 quartiles was regarded as being "metabolically healthy" (MH). Individuals were classified as "obese" (O) or "nonobese" (NO) using a body mass index of 25 kg/m2 as a cut-off. The risk of diabetes at year 8 was assessed according to changes of metabolic health status between year 0 and 4. Multivariate-adjusted relative risks (RRs) (95% confidence interval [CI]) of diabetes were significantly higher in individuals who retained the MONO phenotype (RR 3.72, 95% CI 2.10, 6.60) or who had progressed to MONO from the MHNO phenotype (RR 1.96, 95% CI 1.06, 3.61), whereas it was not significant in individuals who had improved to MHNO from the MONO phenotype (RR 0.67, 95% CI 0.26, 1.74) compared with individuals who retained the MHNO phenotype. In contrast, obese individuals had significantly higher RRs for diabetes, independent of changes in metabolic health status, whereas weight reduction resulted in a decreased risk of diabetes. Sensitivity analysis using the presence or absence of the metabolic syndrome as a definition of metabolic health revealed similar results. Changes in metabolic health status were an independent risk factor for future diabetes in nonobese individuals, whereas general obesity had a greater contribution to the risk of obese individuals developing diabetes. These observations might imply a different intervention strategy for diabetes prevention according to obesity status.

Objective: To determine whether the TyG index, a product of the levels of triglycerides and glucose, may be a valuable marker for identifying metabolically obese but normal weight (MONW) or metabolically healthy but obese (MHO) individuals., Design and Subjects: A total of 17 029 nondiabetic subjects (7185 men and 9844 women) were selected from the Korea National Health and Nutrition Examination Survey conducted in 2008-2010. Individuals with a normal body mass index (BMI) (≥18·5 and <23 kg/m(2) ) and the highest quartile of the homoeostasis model assessment of insulin resistance (HOMA-IR) were classified as MONW. Individuals with obesity (BMI ≥25 kg/m(2) ) and the lowest quartile of HOMA-IR were classified as MHO., Measurements: The TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]., Results: The levels of the TyG index paralleled with various metabolic risk parameters. The index was significantly higher in the MONW group and lower in the MHO group when compared with the non-MONW group and the non-MHO group, respectively. The odds ratios (ORs) of being categorized into the MONW group were approximately fourfold higher in the highest vs lowest quartiles of the TyG index (3·999: 95% CI, 2·508-6·376 in men; 4·737: 95% CI, 3·418-6·565 in women) among normal weight subjects. Conversely, there was a stepwise decrease in the OR of being categorized into the MHO group across the TyG index quartiles among obese subjects., Conclusions: These data highlight the value of the TyG index in discriminating those subjects with higher risks of metabolic diseases., (© 2014 John Wiley & Sons Ltd.)

Aims: We investigated the long-term changes in the prevalence and the control rate of hypertension among Korean adults diagnosed with diabetes., Methods: Using data from the Korean National Health and Nutrition Examination Survey (1998-2008), including 1384 adults diagnosed with diabetes, we analyzed changes in the prevalence of hypertension (mean SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or use of antihypertensive medication) and the control rate of hypertension (BP < 130/80 mmHg)., Results: The prevalence of hypertension in diabetic adults was 50.9% in 1998 and 51.7% in 2008 (P = 0.563). The mean blood pressure decreased from 138.1 ± 1.1/80.0 ± 0.6 mmHg to 124.7 ± 0.8/76.0 ± 0.5 mmHg (P < 0.001); awareness (37.4 to 85.2%, P < 0.001), treatment (37.4 to 81.8%, P < 0.001), and the control rate (20.1 to 34.7%, P = 0.001) steadily increased. The prevalence of hypertension increased significantly more in the obese group compared with the non-obese group (53.3% vs. 49.0% in 1998, P = 0.784; 64.3% vs. 42.0% in 2008, P < 0.0001, respectively, P for trend = 0.0001)., Conclusions: Although the rates of hypertension treatment have significantly improved, the control rate remains inadequate, and intensive intervention is urgently needed., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

In this study, the effects of sitagliptin analogue (SITA) or pioglitazone (PIO) treatment on glucose homeostasis and Β-cell dynamics in animal models of type 2 diabetes--Akita and db/db mice were evaluated. After 4-6 weeks of treatment, both SITA and PIO were shown to lower non-fasting glucose levels and reduced glycemic excursion in the intraperitoneal glucose tolerance test. In addition, both drugs preserved normal islet structure and the proportion of Β-cells in the islets. Compared to the controls, SITA treatment induced a higher Β-cell proliferation rate in Akita mice and a lower rate of apoptosis in db/db mice, whereas PIO treatment induced a lower rate of apoptosis in db/db mice and reduced proliferation rates in Akita mice. In conclusion, both SITA and PIO appear to exert some beneficial effects on the islet structure in addition to glycemic control via different mechanisms that involve Β-cell dynamics in Akita and db/db mice. [BMB reports 2011; 44(11): 713-718].

Objective: To investigate the prevalence and identify the phenotype of individuals suspected to be metabolically obese but normal weight (MONW)., Design and Subjects: Eight thousand nine hundred and eighty-seven nondiabetic subjects aged over 40 years were selected from the Chungju Metabolic disease Cohort study performed in 2003-2006 in Korea. Those within the highest quartile in the homeostasis model assessment of insulin resistance (HOMA-IR) with a normal body mass index (BMI) between 18·5 and 23 kg/m(2) were classified as MONW., Measurements: Data on anthropometry, lipid profiles and HOMA-IR values were analysed., Results: The prevalence of MONW was 14·2% for men and 12·9% for women amongst normal-weight subjects. Multiple logistic regression analysis showed that total cholesterol (TC) levels over 5·17 mm (odds ratio, OR = 1·481; 95% confidence intervals, CI 1·086-2·021), triglyceride (TG) levels over 1·69 mm (OR = 1·507; 95% CI 1·093-2·077) and high-density lipoprotein-cholesterol levels lower than 1·03 mm (OR = 1·580; 95% CI 1·053-2·371) independently had higher odds of diagnosing MONW amongst men. For women, a BMI over 21·5 kg/m(2) (OR = 1·405; 95% CI 1·034-1·909), TC levels over 5·17 mm (OR = 1·524; 95% CI 1·112-2·090) and TG levels over 1·69 mm (OR = 1·799; 95% CI 1·302-2·487) were independently associated with a diagnosis of MONW., Conclusions: More than 10% of normal-weight subjects were classed as MONW in this cohort. Identification of these subjects based on lipid profiles could aid in the early detection of a high risk group of developing cardiometabolic diseases., (© 2011 Blackwell Publishing Ltd.)

Bone morphogenetic protein 4 (BMP-4) is involved in the earliest stages of adipocyte differentiation and is recognized as an adipogenic factor for white adipose tissue. The association of serum BMP-4 levels with anthropometric and metabolic parameters has not been previously studied. We aimed to explore the relationship of serum BMP-4 levels with obesity and metabolic syndrome. Serum BMP-4 levels were measured in 104 non-diabetic individuals from the Chungju Metabolic Disease Cohort Study. Anthropometric measurements and components of metabolic syndrome were assessed in all patients. Serum BMP-4 levels were significantly increased in individuals with obesity or metabolic syndrome. After adjusting for age and gender, serum BMP-4 levels were positively correlated with body mass index, waist circumference (WC), waist-to-hip ratio, fasting plasma insulin, homeostasis model assessment index, and triglycerides and were negatively correlated with high-density lipoprotein (HDL) cholesterol. Among these parameters, WC and HDL cholesterol were found to be independent contributing factors for serum BMP-4 levels. Serum BMP-4 levels were also significantly higher in subjects with positive diagnostic criteria for each component of metabolic syndrome. The area under the receiver operating characteristic curve for BMP-4 was 0.661 (P = 0.022, 95% CI = 0.528 to 0.794) and the cut-off value was 2.84 pg/mL. This is the first demonstration that serum BMP-4 levels are associated with adiposity, insulin resistance, and the presence of metabolic syndrome. Whether BMP-4 may be involved in the pathogenesis of obesity and metabolic syndrome deserves further investigation.

The proportions of people with type 2 diabetes and obesity have increased throughout Asia, and the rate of increase shows no sign of slowing. People in Asia tend to develop diabetes with a lesser degree of obesity at younger ages, suffer longer with complications of diabetes, and die sooner than people in other regions. Childhood obesity has increased substantially and the prevalence of type 2 diabetes has now reached epidemic levels in Asia. The health consequences of this epidemic threaten to overwhelm health-care systems in the region. Urgent action is needed, and advocacy for lifestyle changes is the first step. Countries should review and implement interventions, and take a comprehensive and integrated public-health approach. At the level of primary prevention, such programmes can be linked to other non-communicable disease prevention programmes that target lifestyle-related issues. The cost of inaction is clear and unacceptable.

Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. [ABSTRACT FROM AUTHOR]

Objective. Control of blood pressure is important in old age for prevention of hypertension-associated complications. This study aimed to investigate the factors associated with control of hypertension in elderly people (≥60 years old) diagnosed with hypertension. Methods. The subjects were those who had a self-reported diagnosis of hypertension (532 men and 1078 women) from a stratified random cluster sample of 4201 people aged 60 years or older. Controlled hypertension was defined as a systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg, and SBP <130 mmHg and DBP <80 mmHg for subjects with diabetes. Results. The prevalence of controlled hypertension (25.9%) was low. In older women, the prevalence of isolated uncontrolled SBP was increased. After adjusting for other covariates, uncontrolled hypertension was positively associated with body mass index (BMI≥23 kg/m2), and negatively associated with balanced diet and a past history of cardiovascular disease in men, whereas in women it was positively associated with waist circumference (≥80 cm). Conclusions. In elderly people diagnosed with hypertension general obesity (high BMI) appears to have an important influence on uncontrolled hypertension in men, whereas abdominal obesity (high waist circumference) appears to be an important factor in women. [ABSTRACT FROM AUTHOR]

Abstract: Increases in the prevalence of type 2 diabetes of 30–60% will occur in many Asian-Pacific countries by 2025, driven by urbanisation, sedentary habits and energy-rich diets. Obesity, insulin resistance, metabolic syndrome and diabetes are closely interrelated. Optimal control of diabetes and associated risk factors has reduced the risk of diabetes-related complications. In the UK Prospective Diabetes Study (UKPDS), metformin reduced the risk of macrovascular complications and retrospective analyses have confirmed the efficacy of metformin in improving clinical outcomes in type 2 diabetic patients with a history of cardiovascular disease. This growing body of evidence has led to the recommendation of metformin as optimum initial pharmacotherapy in overweight type 2 diabetic patients. Obesity is less prevalent in the Asian-Pacific population than in Caucasian populations. Nevertheless, metformin has multiple beneficial metabolic effects, which provide sufficient rationale for it to be recommended as the initial oral anti-diabetic pharmacotherapy, alone or in combination, irrespective of body mass index. This recommendation is consistent with global guidelines and regional recommendations for the Asian-Pacific region from the International Diabetes Federation. These recommendations can serve as templates for development of local guidelines for Asian people with diabetes, given the ethnic and cultural diversity within the region. [Copyright &y& Elsevier]