Korean guidelines for the management of gout

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Use of Dual-Energy X-ray Absorptiometry for Body Composition in Chronic Disease Management / 임상당뇨병

Aging and chronic disease are often accompanied by changes in body composition that lead to decreased muscle mass and increased fat mass, even in weight-stable individuals. Both obesity and sarcopenia are important causes of frailty, disability, morbidity, and mortality. Diminished skeletal muscle and expanded visceral fat can act synergistically, which might maximize their effects on physical impairments and metabolic disorders. Dual-energy X-ray absorptiometry (DEXA) was regarded as one of the most versatile imaging techniques for evaluation of sarcopenia and obesity as well as osteoporosis. Whole-body DEXA allows total and regional assessment of the three compartments for fat mass, non-bone lean mass, and bone mineral content. Moreover, DEXA is accurate, reproducible, fast, relatively inexpensive, and involves very low radiation dose to the patient. Developments in DEXA equipment and software allow an accurate and differential estimate of visceral adipose tissue. This review summarizes the clinical practical application of whole-body DEXA values, with use of muscle and fat mass indices in the diagnostic workup of low muscle mass, sarcopenia, and sarcopenic obesity according to the most recent studies and guidelines.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Sulfonylurea, an Update / 임상당뇨병

Sulfonylureas (SUs) are widely prescribed in the treatment of type 2 diabetes. Despite the availability of several newer agents, SUs still play an important role in glucose-lowering therapy. However, over the last decade, there is a degrowth of older agents (SUs and thiazolidinediones) prescriptions with emergence of newer agents such as dipeptidyl peptidase-4 inhibitors, sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. The role of SUs in modern clinical practice poses ongoing clinical debate. With active marketing of these newer drugs, the concerns regarding hypoglycemia, secondary failure and cardiovascular safety tend to be overstated, especially when considering SUs. Some evidence has suggested that modern SUs (such as gliclazide modified release and glimepiride) have lower hypoglycemia and secondary failure rates and decreased risk of mortality from all-cause and cardiovascular disease compared to conventional SUs in patients with type 2 diabetes. Appropriate clinical judgement coupled with a patient-centered approach is crucial to achieve the best outcome in patients with type 2 diabetes. Modern SUs should also be considered based on their safety, efficacy, and low cost when choosing anti-hyperglycemic agents.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Background@#Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. @*Results@#In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. @*Conclusion@#This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study

BACKGROUND@#There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.@*METHODS@#This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.@*RESULTS@#Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).@*CONCLUSION@#Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Advances in Glucose Monitoring and Insulin Therapy in Intensive Care Unit Patients / 임상당뇨병

Since the multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study was published, the pursuit of tight glycemic control (TGC) among intensive care unit (ICU) patients has been seen as counterproductive and moderate glycemic control has become standard practice in ICUs. However, thus far, there is good evidence that hypoglycemia and hyperglycemia are associated with worse outcomes in ICU patients. Recently, the importance of improving time in band and reducing hypoglycemic episodes and glycemic variability has been more recognized. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can have greater clinical benefit in terms of the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and accurately. In this review, modern methods for glucose control in the ICU are presented, as well as future perspectives including the development of CGM and semiautomated glucose control, such as closed-loop systems.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

Pharmacological Management of Obesity in Patients with Type 2 Diabetes: An Update

Type 2 diabetes is closely linked with obesity. Obesity is associated with risk of both development and progression of type 2 diabetes, as well as cardiovascular disease. Although lifestyle modifications aimed at prompting weight reduction are cornerstone therapies in managing type 2 diabetes, weight reduction remains challenging for overweight and obese patients with type 2 diabetes. A shift in the approach to weight management in patients with type 2 diabetes is clearly needed. Pharmacotherapy should be considered as a realistic treatment option for patients with type 2 diabetes who cannot lose weight with health behavior modification alone. This review is focused on current pharmacotherapies for obesity to support the glycemic and weight loss goals of obese people with type 2 diabetes.

Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

Co-Culture of alpha TC-6 Cells and beta TC-1 Cells: Morphology and Function

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

Diverse Abnormal Body Composition Phenotypes: Interaction Between Muscle, Fat, and Bone

Sarcopenia, obesity, and osteoporosis, the three disorders of body composition, are growing in prevalence. Osteoporosis and obesity were thought to be mutually exclusive conditions, as were sarcopenia and obesity. However, these disorders are commonly observed in the aging process and recent studies have indicated a potential interconnection among them with interaction between muscle, bone, and fat. Therefore, it would not be appropriate to discuss sarcopenia, obesity, and osteoporosis without bearing in mind the complex interactions of muscle, fat, and bone tissue. Due to the complicated interaction among them, the phenotypes have been given various names depending on the proposed cause or the combination of sarcopenia, obesity and osteoporosis. Therefore, we introduce new terms concerning the diverse phenotypes of body composition. In addition, this paper describes the interaction between muscle, fat and bone from a hormonal aspect and in terms of the whole body. Unraveling the link between muscle, fat, and bone at both the micro and macro level will elucidate the reasons for abnormal body composition phenotypes, and further enhance new therapeutic options for sarcopenia, obesity, and osteoporosis.

Waist-to-Height Ratio is a Valuable Marker for Predicting Cardiometabolic Disease

No abstract available.

Sarcopenia in Korea: Prevalence and Clinical Aspects

Sarcopenia has been defined as the considerable loss of skeletal muscle mass and strength that results in frailty in the elderly. Because muscle tissue plays diverse important roles in human, sarcopenia presents many negative health-related consequences including impaired energy homeostasis, falls and cardiovascular disease, and subsequently higher mortality. It is becoming evident that sarcopenia has a negative impact on the healthy life of the elderly. The European Working Group on Sarcopenia, the International Working Group on Sarcopenia and the Asian Working Group on Sarcopenia have released position statement regarding sarcopenia, and more recently the Foundation for the National Institutes of Health Sarcopenia Project has provided a new guideline for assessment of sarcopenia. At this time, there have been several data delineating the status of sarcopenia in Korea. This review focuses on largescale cohorts that assessed sarcopenia and highlights the controversies surrounding the clinical definition and prevalence of sarcopenia in Korea.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance

BACKGROUND/AIMS: The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). METHODS: A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose > or = 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). RESULTS: The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index beta-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p < or = 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. CONCLUSIONS: Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both beta-cell dysfunction and insulin resistance.

A1c Variability Can Predict Coronary Artery Disease in Patients with Type 2 Diabetes with Mean A1c Levels Greater than 7

BACKGROUND: Recent studies suggested that the association of acute glucose variability and diabetic complications was not consistent, and that A1c variability representing long term glucose fluctuation may be related to coronary atherosclerosis in patients with type 1 diabetes. In this study, we attempt to determine whether or not A1c variability can predict coronary artery disease (CAD) in patients with type 2 diabetes. METHODS: We reviewed data of patients with type 2 diabetes who had undergone coronary angiography (CAG) and had been followed up with for 5 years. The intrapersonal standard deviation (SD) of serially-measured A1c levels adjusted by the different number of assessments among patients (adj-A1c-SD) was considered to be a measure of the variability of A1c. RESULTS: Among the 269 patients, 121 of them had type 2 diabetes with CAD. In patients with A1c > or =7%, the mean A1c levels and A1c levels at the time of CAG among the three groups were significantly different. The ratio of patients with CAD was the highest in the high adj-A1c-SD group and the lowest in the low adj-A1c-SD group (P=0.017). In multiple regression analysis, adj-A1c-SD was an independent predictor for CAD in subjects with A1c > or =7% (odds ratio, 2.140; P=0.036). CONCLUSION: Patients with higher A1c variability for several years showed higher mean A1c levels. A1c variability can be an independent predictor for CAD as seen in angiographs of patients with type 2 diabetes with mean A1c levels over 7%.

Sarcopenia: Definition, Epidemiology, and Pathophysiology

The epidemiological trends that characterize our generation are the aging of the population. Aging results in a progressive loss of muscle mass and strength called sarcopenia, which is Greek for 'poverty of flesh'. Sarcopenia could lead to functional impairment, physical disability, and even mortality. Today, sarcopenia is a matter of immense public concern for aging prevention. Its prevalence continues to rise, probably as a result of increasing elderly populations all over the world. This paper addressed the definition and epidemiology of sarcopenia and its underlying pathophysiology. In addition, we summarized the abundant information available in the literature related to sarcopenia, together with results from Korean sarcopenic obesity study (KSOS) that we performed.

Sarcopenic Obesity / 임상당뇨병

Obesity is a major public health problem. The population is growing older, and the prevalence of obesity in the elderly is rising. In normal aging, changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass. This age-related progressive loss of muscle mass and strength is called sarcopenia. Sarcopenic obesity, which describes the process of muscle loss combined with increased body fat as people age, is associated with loss of strength and function, reduced quality of life, and even mortality. The pathogenesis of sarcopenic obesity is complex and involves multiple interactions between lifestyle, endocrine, and immunological factors. Recent epidemiological studies suggest that sarcopenic obesity is related to accelerated functional decline and high risk of diseases and mortality and, therefore, the identification of affected older patients should be an essential goal of clinicians. This paper addresses the definition and epidemiology of sarcopenic obesity and its underlying pathophysiology. In addition, this article describes the clinical significance and management strategies of sarcopenic obesity.