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Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. Methods The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes self-management through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. Results Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. Conclusion This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Abstract The β‐cell relies predominantly on glucose utilization to generate adenosine triphosphate, which is crucial for both cell viability and insulin secretion. The β‐cell has evolved remarkable metabolic flexibility to productively respond to shifts in environmental conditions and changes in glucose availability. Although these adaptive responses are important for maintaining optimal cellular function, there is emerging evidence that the resulting changes in cellular metabolites can impact the epigenome, causing transient and lasting alterations in gene expression. This review explores the intricate interplay between metabolism and the epigenome, providing valuable insights into the molecular mechanisms leading to β‐cell dysfunction in diabetes. Understanding these mechanisms will be critical for developing targeted therapeutic strategies to preserve and enhance β‐cell function, offering potential avenues for interventions to improve glycemic control in individuals with diabetes.

ABSTRACT Aims The aim of this study was to better understand how the chemotherapy drug doxorubicin contributes to the development of β‐cell dysfunction and to explore its relationship with mitochondrial aldehyde dehydrogenase‐2 (ALDH2). Materials and Methods In order to investigate this hypothesis, doxorubicin was administered to INS‐1 cells, a rat insulinoma cell line, either with or without several target protein activators and inhibitors. ALDH2 activity was detected with a commercial kit and protein levels were determined with western blot. Mitochondrial ROS, membrane potential, and lipid ROS were determined by commercial fluorescent probes. The cell viability was measured by CCK‐assay. Results Exposure of INS‐1 cells to doxorubicin decreased active insulin signaling resulting in elevated ALDH2 degradation, compared with control cells by the induction of acid sphingomyelinase mediated ceramide induction. Further, ceramide induction potentiated doxorubicin induced mitochondrial dysfunction. Treatment with the ALDH2 agonist, ALDA1, blocked doxorubicin‐induced acid sphingomyelinase activation which significantly blocked ceramide induction and mitochondrial dysfunction mediated cell death. Treatment with the ALDH2 agonist, ALDA1, stimulated casein kinase‐2 (CK2) mediated insulin signaling activation. CK2 silencing neutralized the function of ALDH2 in the doxorubicin treated INS‐1 cells. Conclusions Mitochondrial ALDH2 activation could inhibit the progression of doxorubicin induced pancreatic β‐cell dysfunction by inhibiting the acid sphingomyelinase induction of ceramide, by regulating the activation of CK2 signaling. Our research lays the foundation of ALDH2 activation as a therapeutic target for the precise treatment of chemotherapy drug induced β‐cell dysfunction.

BackgroundCardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD).MethodWe enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR

Background To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P

Progression of β-cell loss in diabetes mellitus is significantly influenced by persistent hyperglycemia. At the cellular level, a number of signaling cascades affect the expression of apoptotic genes, ultimately resulting in β-cell failure; these cascades have not been elucidated. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) plays a central role in the detoxification of reactive aldehydes generated from endogenous and exogenous sources and protects against mitochondrial deterioration in cells. Here we report that under diabetogenic conditions, ALDH2 is strongly inactivated in β-cells through CDK5-dependent glutathione antioxidant imbalance by glucose-6-phosphate dehydrogenase (G6PD) degradation. Intriguingly, CDK5 inhibition strengthens mitochondrial antioxidant defense through ALDH2 activation. Mitochondrial ALDH2 activation selectively preserves β-cells against high-glucose-induced dysfunction by activating AMPK and Hydrogen Sulfide (H2S) signaling. This is associated with the stabilization and enhancement of the activity of G6PD by SIRT2, a cytoplasmic NAD+-dependent deacetylase, and is thereby linked to an elevation in the GSH/GSSG ratio, which leads to the inhibition of mitochondrial dysfunction under high-glucose conditions. Furthermore, treatment with NaHS, an H2S donor, selectively preserves β-cell function by promoting ALDH2 activity, leading to the inhibition of lipid peroxidation by high-glucose concentrations. Collectively, our results provide the first direct evidence that ALDH2 activation enhances H2S-AMPK-G6PD signaling, leading to improved β-cell function and survival under high-glucose conditions via the glutathione redox balance.

Background To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. Methods This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. Results The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P

Objective This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia.Patients and methods This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (>14 days) were also assessed.Results The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (n = 89) and was not different according to the presence of diabetes (DM vs. non-DM) or HbA1c levels (≥7.5 vs. .05). However, the mortality rate was significantly higher in patients with high GV (CV ≥ 36%) than in those with low GV (CV < 36%; 37.5 vs. 25.4%, p = .028). The risk of mortality in patients with high GV was prominent in the subgroups with DM or low HbA1c levels. Among the surviving patients (n = 193), 44 remained in the ICU for more than 14 days. Compared to low GV, high GV was associated with a higher rate of prolonged ICU stay, although not statistically significant (27.8 vs. 18.5%, p = .171). After adjusting for the severity of illness and treatment strategy, CV was an independent risk factor for 28-day mortality (hazard ratio [HR], 1.01, p = .04) and prolonged ICU stay (odds ratio, 1.02; p = .04).Conclusions High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (

Abstract Background The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. Methods This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004–2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012–2016). Results The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p

Background This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults. Methods We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018. Results Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c)

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

Background A diabetic foot is the most common cause of non-traumatic lower extremity amputations (LEA). The study seeks to assess the risk factors of amputation in patients with diabetic foot ulcers (DFU). Methods The study was conducted on 351 patients with DFUs from January 2010 to December 2018. Their demographic characteristics, disease history, laboratory data, ankle-brachial index, Wagner classification, osteomyelitis, sarcopenia index, and ulcer sizes were considered as variables to predict outcome. A chi-square test and multivariate logistic regression analysis were performed to test the relationship of the data gathered. Additionally, the subjects were divided into two groups based on their amputation surgery. Results Out of the 351 subjects, 170 required LEA. The mean age of the subjects was 61 years and the mean duration of diabetes was 15 years; there was no significant difference between the two groups in terms of these averages. Osteomyelitis (hazard ratio [HR], 6.164; 95% confidence interval [CI], 3.561−10.671), lesion on percutaneous transluminal angioplasty (HR, 2.494; 95% CI, 1.087−5.721), estimated glomerular filtration rate (eGFR; HR, 0.99; 95% CI, 0.981−0.999), ulcer size (HR, 1.247; 95% CI, 1.107−1.405), and forefoot ulcer location (HR, 2.475; 95% CI, 0.224−0.73) were associated with risk of amputation. Conclusion Osteomyelitis, peripheral artery disease, chronic kidney disease, ulcer size, and forefoot ulcer location were risk factors for amputation in diabetic foot patients. Further investigation would contribute to the establishment of a diabetic foot risk stratification system for Koreans, allowing for optimal individualized treatment.

BackgroundTo determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM.MethodsThis was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group.ResultsAfter exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P

Impaired β-cell function is the key pathophysiology of type 2 diabetes mellitus, and chronic exposure of nutrient excess could lead to this tragedy. For preserving β-cell function, it is essential to understand the cause and mechanisms about the progression of β-cells failure. Glucotoxicity, lipotoxicity, and glucolipotoxicity have been suggested to be a major cause of β-cell dysfunction for decades, but not yet fully understood. Fatty acid translocase cluster determinant 36 (CD36), which is part of the free fatty acid (FFA) transporter system, has been identified in several tissues such as muscle, liver, and insulin-producing cells. Several studies have reported that induction of CD36 increases uptake of FFA in several cells, suggesting the functional interplay between glucose and FFA in terms of insulin secretion and oxidative metabolism. However, we do not currently know the regulating mechanism and physiological role of CD36 on glucolipotoxicity in pancreatic β-cells. Also, the downstream and upstream targets of CD36 related signaling have not been defined. In the present review, we will focus on the expression and function of CD36 related signaling in the pancreatic β-cells in response to hyperglycemia and hyperlipidemia (ceramide) along with the clinical studies on the association between CD36 and metabolic disorders.

Prolonged hyperglycemia plays a major role in the progression of β-cell loss in diabetes mellitus. Here we report an insulin sensitizer thiazolidinedione Pioglitazone selectively preserves the beta cells against high glucose-induced dysfunction by activation of AMPK and Glutaminase 1 (GLS1) axis. AMPK activation increases the stability of Glutaminase 1 by HSP90 family mitochondrial heat shock protein 75 (HSP75/TRAP1). This is associated with an elevation of GSH/GSSG ratio which leads to inhibition of mitochondrial dysfunction by induction of BCL2/BCL-XL in high glucose conditions. Pioglitazone was able to also protect against high glucose-induced elevations in maladaptive ER stress markers and increase the adaptive unfolded protein response (UPR) by inhibiting mTORC1-eEF2 protein translation machinery. Moreover, the pioglitazone effect on AMPK activation was not dependent on the PPARγ pathway. Strikingly, chemical inhibition of AMPK signaling or glutaminase-1 inhibition abrogates the pioglitazone effect on the TRAP1-GLS1 axis and GSH/GSSG ratio linked to mitochondrial dysfunction. Finally, inhibition of AMPK signaling enhanced maladaptive ER stress markers by mTORC1-eEF2 activation. Altogether, these results support the proposal that pioglitazone induced AMPK activation stabilizes a novel interaction of TRAP1/HSP75-GLS1 and its downstream signaling leads to improved β-cell function and survival under high glucose conditions.

BackgroundThe objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.MethodsThis study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.ResultsIn 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c

BackgroundChronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5.MethodsTo address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis.ResultsActivation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss.ConclusionMyricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.

Aims: Our aim was to investigate the effects of peripheral arterial stiffness on the risk of progression of renal disease in patients with type 2 diabetes (T2D).Methods: This was a single center, retrospective cohort study. Brachial-ankle pulse wave velocity (baPWV) tests were performed on T2D patients in 2015. Increased arterial stiffness was defined as baPWV of ≥ 1800 cm/s. We applied criteria for progression of renal disease according to EMPA-REG OUTCOME trial.Results: In total, 186 patients were enrolled in the final study. The mean age was 59.1 years and male:female ratio was 1.73:1. Thirteen (7%) patients progressed to renal disease during the average follow-up time of 35.3 months. In particular, the risk of progression to macroalbuminuria was significantly higher in the baPWV ≥ 1800 cm/s group (HR 6.216, p = 0.020). Individuals with a baPWV of ≥ 1800 cm/s (when comparisons were adjusted for age, sex, blood pressure, diabetes duration, eGFR, and use of renin-angiotensin system inhibitors) had a significantly higher risk of the progression of renal disease (HR = 8.480, p = 0.014).Conclusion: These results suggest that peripheral arterial stiffness (baPWV ≥ 1800 cm/s) may be a risk factor for the progression of renal disease in T2D patients.

BackgroundThis report presents the recent prevalence and comorbidities related to diabetes in Korea by analyzing the nationally representative data.MethodsUsing data from the Korea National Health and Nutrition Examination Survey for 2013 to 2014, the percentages and the total number of subjects over the age of 30 years with diabetes and prediabetes were estimated and applied to the National Population Census in 2014. Diagnosis of diabetes was based on fasting plasma glucose (≥126 mg/dL), current taking of antidiabetic medication, history of previous diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. Impaired fasting glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125 mg/dL among those without diabetes.ResultsAbout 4.8 million (13.7%) Korean adults (≥30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults had IFG. However, 29.3% of the subjects with diabetes are not aware of their condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most subjects with diabetes (89.1%) were under medical treatment, and mostly being treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated. With respect to overall glycemic control, 43.5% reached the target of HbA1c

BackgroundThis study aims to describe the trends in the severity and treatment modality of patients with diabetic foot ulcer (DFU) at a single tertiary referral center in Korea over the last 10 years and compare the outcomes before and after the introduction of a multidisciplinary diabetic foot team.MethodsIn this retrospective observational study, electronic medical records of patients from years 2002 to 2015 at single tertiary referral center were reviewed. Based on the year of first admission, patients were assigned to a group either before or after the year 2012, the year the diabetes team launched.ResultsOf the 338 patients with DFU, 229 were first admitted until the year 2011 (group A), while 109 were first admitted since the year 2012 (group B). Mean age was higher in group B, and ulcer size was larger than those of group A. Whereas duration of diabetes was longer in group B, glycemic control was improved (mean glycosylated hemoglobin, 9.48% vs. 8.50%). The proportion of minor lower extremity amputation (LEA) was increased, but length of hospital stay was decreased (73.7±79.6 days vs. 39.8±36.9 days). As critical ischemic limb increased, the proportion of major LEA was not decreased.ConclusionImproved glycemic control, multidisciplinary strategies with prompt surgical treatment resulted in reduced length of hospital stay, but these measures did not reduce major LEAs. The increase in critical ischemic limb may have played a role in the unexpected outcome, and may suggest the need for increased vascular intervention strategies in DFU treatment.

BackgroundPlasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance.MethodsThis was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was ‘ln [FPG (mg/dL)×triglyceride (mg/dL)/2],’ and the sCD36 index was ‘ln [sCD36 (pg/mL)×FPG (mg/dL)/2].’ResultsOne hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P

We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30 mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Keywords: Rac1, NADPH oxidase, Beta-cell dysfunction, CD36, Oxidative stress

Many studies have demonstrated that an alteration in hemorheological properties is closely correlated with diabetic microcirculatory diseases. However, most of these studies have been limited to animal studies or used a small number of clinical samples, due to a lack of effective point-of-care (POC) devices to measure such properties within clinical environments. Owing to recent developments in microfluidic technology, several hemorheological POC devices have been designed that allow for the possibility of conducting extensive clinical studies using hemorheological measurements. Here, we reviewed recent clinical studies of diabetic kidney disease (DKD) associated with hemorheological parameters. We found that RBC deformability alone did not show a significant difference according to the degree of DKD, whereas critical shear stress (CSS) was found to be closely related to the ratio of albumin to creatinine and glomerular filtration rate. We also reviewed studies that alteration of hemorheological properties are associated with the development of DKD, which showed that CSS could be considered as a potential index to diagnose other diabetic complications as well as DKD.

INTRODUCTION:Low urine pH (UpH) and high serum uric acid are considered evidence of metabolic disorders. The effect of low UpH on the development of metabolic syndrome (MetS) is less clear than that of high serum uric acid. We investigated the association between low UpH on the development of MetS and its components: central obesity, dyslipidemia, hypertension, and dysglycemia. METHODS:Two studies were conducted based on 2 datasets. The cross-sectional study included 14,511 subjects aged 19-80 years, based on the Korea National Health and Nutrition Examination Survey in 2013-2015. The retrospective cohort study included 3,453 subjects aged 19-80 years without MetS at the first checkup, who underwent at least 3 health checkups at a single tertiary hospital between 2011 and 2017. UpH was measured using an automatic urine analyzer in the range of 5.0-9.0 at first visit. RESULTS:In the cross-sectional study, low UpH (= 5.0) was associated with the prevalence of MetS (odds ratio [OR] = 1.480, 95% confidence interval [CI] 1.334-1.643, p

Type 2 diabetes (T2D) has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from α-cell has languished whereas β-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant α-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted α-cell suppression. During hypoglycemia, insufficient counter-regulation response is also observed in advanced T2D. Though many debates still remained for exact mechanisms behind the dysregulation of α-cell in T2D, it is clear that the blockade of glucagon receptor or suppression of glucagon secretion from α-cell would be novel therapeutic targets for control of hyperglycemia. Whereas there have not been remarkable advances in developing new class of drugs, currently available glucagon-like peptide-1 and dipeptidyl peptidase-IV inhibitors could be options for treatment of hyperglucagonemia. In this review, we focus on α-cell dysfunction and therapeutic potentials of targeting α-cell in T2D.

BackgroundThe aim of this study is to observe the outcome of critically ill patients in relation to blood glucose level at admission and to determine the optimal range of blood glucose at admission predicting lower hospital mortality among critically ill patients.MethodsWe conducted a retrospective cohort study of a total 1,224 subjects (males, 798; females, 426) admitted to intensive care unit (ICU) from 1 January 2009 to 31 December 2010. Blood glucose levels at admission were categorized into four groups (group 1,

BackgroundNonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD.MethodsAmong 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI).ResultsOf the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and metabolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence interval, 0.029 to 0.049).ConclusionSkeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

BackgroundRecently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C), albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes.MethodsWe enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (

BackgroundA 64-slice multidetector computed tomography (MDCT) is well known to be a useful noninvasive form of angiography for the general population, but not for certain patients with diabetes. The aim of this study was to investigate the diagnostic accuracy and usefulness of 64-slice MDCT coronary angiography for detecting coronary artery disease in Korean patients with type 2 diabetes mellitus (T2DM).MethodsA total of 240 patients were included, 74 of whom had type 2 diabetes (M:F=40:33; 41.8±9.5 years). We compared significant coronary stenosis (>50% luminal narrowing) in MDCT with invasive coronary angiography (ICA) by segment, artery, and patient. We also evaluated the influence of obesity and coronary calcium score on MDCT accuracy.ResultsOf the 4,064 coronary segments studied, 4,062 segments (T2DM=1,109) were assessed quantitatively by both MDCT and ICA, and 706 segments (T2DM=226) were detected as a significant lesion by ICA in all patients. Sensitivity, specificity, as well as positive and negative predictive values for the presence of significant stenosis in T2DM were: by segment, 89.4%, 96.4%, 85.8%, and 97.4%, respectively; by artery (n=222), 95.1%, 92.9%, 94.4%, and 93.8%, respectively; by patients (n=74), 98.4%, 100.0%, 98.4%, and 90.0%, respectively. Regardless of presence of diabetes, there was no significant difference in diagnostic accuracy. Obesity (≥25 kg/m2) and coronary calcium score did not also affect the diagnostic accuracy of MDCT.ConclusionThe 64-slice MDCT coronary angiography was found to have similar diagnostic accuracy with ICA, regardless of diabetes. These results suggest MDCT may be helpful to reduce unnecessary invasive studies for patients with diabetes.

BackgroundMetformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.MethodsTo evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.ResultsAn ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.ConclusionOur results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

BackgroundThe hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.MethodsTo evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel.ResultsThe hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.ConclusionThese results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

BackgroundFood exchange lists are one of the main methods of nutritional education. However, Korean food exchange lists have not been revised since 1994. Therefore, we surveyed the opinions of diabetes educators and patients with diabetes regarding the need for revision of the current food exchange lists.MethodsFor two weeks beginning on 10 March 2008, a 12-item questionnaire regarding the opinion and need for revision of the current food exchange lists was e-mailed to diabetes educators nationwide. Another 15-question survey was administered to patients with diabetes in 13 hospitals located in the Seoul and Gyeonggi regions of Korea.ResultsWe obtained survey responses from 101 diabetes educators and 209 patients; 65 (64.3%) of the educators answered that the current food exchange lists should be revised. The items that needed revision were the glycemic index, addition of new foods and reaffirmation of exchange standard amounts. The patients demanded specific education about choosing appropriate foods, a balanced meal plan, proper snacks, and dining intake.ConclusionOur survey results demonstrate the need to revise the Korean food exchange lists. This process should focus on glycemic index, the addition of new foods and reconfirmation of one exchange reference unit.

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