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Background@#This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. @*Methods@#In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. @*Results@#The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. @*Conclusion@#Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.
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Background@#Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. @*Methods@#In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). @*Results@#Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. @*Conclusion@#Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.
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Background@#Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM. @*Methods@#A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured. @*Results@#Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01). @*Conclusion@#The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.
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Background@#Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate. @*Methods@#The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed. @*Results@#In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population. @*Conclusion@#The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.
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Purpose@#To date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors. @*Materials and Methods@#This study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively. @*Results@#After 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function. @*Conclusion@#Adding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.
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Background/Aims@#Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. @*Methods@#Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveysdatabase were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥–0.640. ASCVD risk was evaluated using the American College of Cardiol-ogy/American Heart Association guidelines. @*Results@#The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). @*Conclusions@#Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
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Stroke is one of the major complications of diabetes and increases morbidity and mortality. Hyperglycemia confers increased risk of stroke occurrence. Furthermore, cardiometabolic risk factors such as hypertension and dyslipidemia frequently coexist in patients with diabetes and increase the risk of stroke. Some recent cardiovascular outcome trials of newer anti-diabetic medications have shown beneficial effects on cardiovascular complications. Prevention and improving outcomes of stroke in patients with diabetes requires proper management of hyperglycemia and additional risk factors. This review is an evidence-based approach to the epidemiology, glycemic control, effects of anti-diabetic medications on stoke, and risk factor management for prevention and improving outcomes of stroke for patients with diabetes.The prevalence of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is rapidly increasing in Korean populations and is estimated to reach 39% among Korean adults. NAFLD is one of the strongest risk factors of type 2 diabetes mellitus (T2DM), and the presence of NAFLD in T2DM patients is associated with a worse natural course of diabetic complications. The gold standard for diagnosing NAFLD is liver biopsy, which involves sampling error, high cost, and other disadvantages related to its invasive nature. We summarize non-invasive diagnostic NAFLD algorithms including biomarkers and four major imaging tools (ultrasonography, computed tomography, magnetic resonance imaging, and liver FibroScanⓇ) for diagnosing NAFLD including hepatic fibrosis. To prevent NASH (nonalcoholic steatohepatitis) or liver fibrosis, a combination of lifestyle modification with a low caloric diet and exercise, anti-diabetic agents, and non-anti-diabetic agents should be applied.
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Purpose@#Menstruation is associated with menstrual symptoms like pain and balance problems which have an impact on the quality of life. Pilates increases pelvic stability and reduces menstrual pain by inducing abdominal muscle contraction. This study was done to evaluate the effects of Pilates on menstrual pain, symptoms, balance, and quality of life when compared to aerobic exercise. @*Methods@#Thirty-nine women with menstrual pain were randomly divided into the Pilates group (n = 13), aerobics group (n = 13), and control group (n = 13). The Pilates group performed lumbar-pelvic stabilization exercises, while the aerobic group ran on a treadmill. The control group did not undergo any intervention. The experimental groups exercised for four weeks (12 sessions) and did not exercise during menstruation. The Y-balance test was performed on the second day of menstruation to evaluate dynamic balance. The questionnaires administered immediately after menstruation were the visual analog scale (VAS), Korea Oswestry Disability Index (ODI), and the modified Menstrual Distress Questionnaire (MDQ). The paired t-test was used to compare the effect of exercise within the three groups and a oneway analysis of variance was used to compare between groups. @*Results@#VAS and MEDI-Q scores significantly decreased in the Pilates group after 4 weeks compared with those in the aerobic and control groups. Moreover, ODI and Y-balance scores increased in the Pilates group compared with those in the aerobic and control groups (p < 0.05). @*Conclusion@#The Pilates stabilization exercises are effective and help in improving menstrual pain, balance and other menstrual symptoms assessed through ODI, and MEDI-Q, compared to aerobic exercises.
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Background@#Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism. @*Methods@#Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks. @*Results@#The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue. @*Conclusion@#SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.
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Cardiac arrhythmia is a rare manifestation of the Wallenberg syndrome; lesions are located in the brainstem, especially the lower medulla, which regulates sympathetic and parasympathetic activity. A 55-year-old man was admitted to the university hospital with symptoms including ataxia, left ptosis, decreased sensation of pain and temperature on the right side, left facial numbness, and dizziness. Brain magnetic resonance imaging revealed an infarction in the left dorsolateral medulla. Therefore, he was diagnosed with Wallenberg syndrome. While he underwent conservative treatment for Wallenberg syndrome, he experienced several events of self-limiting heart pounding, which required an evaluation of cardiac function. The 24-hour Holter monitor showed an increased RR interval with bradycardia and prolonged sinus pause. As a result, the diagnosis of sick sinus syndrome combined with Wallenberg syndrome was made. Sick sinus syndrome is a rare cardiac complication of the Wallenberg syndrome, and clinicians could overlook it when the initial electrocardiography shows a normal sinus rhythm. Sick sinus syndrome can cause sudden death without appropriate medical intervention. Therefore, clinicians should consider further evaluation, including a 24-hour Holter monitor, to check for the potential presence of sick sinus syndrome in the acute phase of Wallenberg syndrome.
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Background/Aims@#In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities. @*Methods@#There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine. @*Results@#The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications. @*Conclusions@#The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.
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The neurotoxicity of nitrous oxide (N2O) is known to be mainly occurred by interference with action of vitamin B12. A 38-year-old male presented with progressive gait instability after recreational inhalational use of N2O for 2 months. Although spine magnetic resonance image showed typical subacute combined degeneration, nerve conduction study showed motor neuropathy that is atypical findings of vitamin B12 deficiency. This case suggests N2O-induced neuropathy can develop separately from a vitamin B12 deficiency.
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BackgroundGlycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.MethodsIn this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).ResultsAt week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, PPPConclusionDapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.
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The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
ABSTRACT
The neurotoxicity of nitrous oxide (N2O) is known to be mainly occurred by interference with action of vitamin B12. A 38-year-old male presented with progressive gait instability after recreational inhalational use of N2O for 2 months. Although spine magnetic resonance image showed typical subacute combined degeneration, nerve conduction study showed motor neuropathy that is atypical findings of vitamin B12 deficiency. This case suggests N2O-induced neuropathy can develop separately from a vitamin B12 deficiency.
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BackgroundGlycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.MethodsIn this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).ResultsAt week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, PPPConclusionDapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.
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The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
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BackgroundThe aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).MethodsA total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (ResultsMedian age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age P=0.022). The eGFR was inversely associated with disease duration whilst the degree of decrease was more prominent in the childhood/adolescent-onset group than in the later onset group (aged 30 to 40 years; PP=0.005).ConclusionIn individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.
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Objective@#To investigate the epidemiologic and demographic characteristics of patients with spinal cord injury (SCI) who were admitted to a department of rehabilitation of a university hospital. @*Methods@#This was a descriptive cross-sectional study. Medical records including sex, age at injury, type of disability, traumatic or non-traumatic etiology and presence of ossification of posterior longitudinal ligament (OPLL) of patients with SCI who were admitted to the department of rehabilitation between 2012 and 2018 were reviewed. @*Results@#Of the 221 cases of SCI, 161 were traumatic and 60 were non-traumatic. The mean age at injury was 52.8 years. People aged 40–49 years showed highest proportion among overall SCI patients (19.0%). The proportion of male patients was higher in traumatic SCI at 4.96:1 than in non-traumatic SCI at 1.30:1. The most common cause of traumatic SCI was falling off (37.3%), followed by motor vehicle crash (35.4%) and tripping over (19.3%). Meanwhile, the most common cause of non-traumatic SCI was neoplasm (35.0%). Tripping over was the leading cause of traumatic SCI in patients aged ≥60 years (42.6%). A high proportion of traumatic SCI patients were found to have underlying OPLL (26.1%), particularly those who were injured by tripping over (64.5%). @*Conclusion@#The mean age of SCI patients was higher than that of previous studies. Falls was the single most common cause of traumatic SCI, and tripping over was the most common cause of injury in the elderly patients. OPLL was prevalent in patients who were injured from tripping over.
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Background/Aims@#In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities. @*Methods@#There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine. @*Results@#The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications. @*Conclusions@#The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.