Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus.

Background: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. Conclusion: In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12. RESULTS: HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group. CONCLUSION: An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.

The impact of diabetes status on total and site-specific cancer risk in the elderly population: A nationwide cohort study.

AIMS: We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. METHODS: This study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. RESULTS: The risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65-74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. CONCLUSIONS: Diabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.

Impacts of gender and lifestyle on the association between depressive symptoms and cardiovascular disease risk in the UK Biobank.

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.

Associations of polyneuropathy with risk of all-cause and cardiovascular mortality, cardiovascular disease events stratified by diabetes status.

AIMS/INTRODUCTION: We investigated the association of polyneuropathy (PN) with all-cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status. MATERIALS AND METHODS: This prospective cohort study used the UK Biobank. Polyneuropathy was defined based on nurse-led interviews or ICD codes for polyneuropathy. Cox proportional hazards models were used to investigate the association of polyneuropathy with clinical outcomes. RESULTS: A total of 459,127 participants were included in the analysis. Polyneuropathy was significantly associated with all-cause and cardiovascular mortality, and with CVD events even after adjusting for CVD risk factors across all diabetes statuses. Metabolic parameters HbA1c , waist circumference, BMI and the inflammatory parameter C-reactive protein showed significant mediation effects for the association between polyneuropathy and CVD. Adherence to a favorable lifestyle was associated with a lower risk of all-cause and cardiovascular mortality regardless of polyneuropathy status. CONCLUSIONS: Polyneuropathy was associated with all-cause and cardiovascular mortality, and with CVD events in subjects with diabetes or prediabetes, even those having normal glucose tolerance. This study suggests the importance of polyneuropathy as a risk factor for death and highlights the necessity of early diagnosis and lifestyle intervention for those with type 2 diabetes and polyneuropathy.

Pancreatic stellate cells promote pancreatic ß-cell death through exosomal microRNA transfer in hypoxia.

Hypoxia in pancreatic islets (islet hypoxia) can occur in type 2 diabetes mellitus. Previously, our in vitro experiments demonstrated that pancreatic stellate cells (PSCs) within the islet are activated in hypoxia, promoting pancreatic ß-cell death. Here, we aimed to demonstrate the in vivo activation of intra-islet PSCs and investigate the mechanism of PSC-induced ß-cell death in hypoxia. A novel in vivo model of islet hypoxia was established by injecting fluorescent microspheres into a carotid artery of Balb/c mice (Microsphere mice). The intraperitoneal glucose tolerance (IPGTT) was performed, and pancreatic tissues were stained for insulin expression after tissue clearing. Pimonidazole staining was also performed in the pancreas to detect the presence of hypoxia in islets. Next, primary PSCs were isolated and cultured from Balb/c mice. Exosomes were isolated from culture media from PSCs cultured in hypoxia (1% oxygen). MicroRNAs (miRNAs) were prepared from exosomes from PSCs, and miRNA expression profiles were analyzed by miRNA sequencing. Several miRNAs were overexpressed in islets using miRNA mimics. Two weeks after injection of microspheres, the Microsphere mice showed worsening of glucose tolerance in IPGTT. Later, cataracts were developed in the eyes of the mice. The pancreas showed that the areas, perimeters, and diameters of insulin-positive cells decreased in Microsphere mice. Pimonidazole adducts were detected in the islets of these mice, indicating the presence of islet hypoxia. In addition, α-smooth muscle actin-positive cell numbers per islet were higher in Microsphere mice, confirming the in vivo activation of intra-islet PSCs in hypoxia. Mouse islets incubated with exosomes isolated from PSCs cultured in hypoxia showed a decrease in cell viability. The exosomes contained a variety of miRNAs, of which miR-23a-3p was found to notably increase ß-cell death through apoptosis. Together, our in vivo and in vitro data provide evidence to support that PSCs within the islets are activated in hypoxia and promote ß-cell death through exosomal miRNA transfer, which may contribute to the progression of type 2 diabetes mellitus.

Impact of hypoglycemia at the time of hospitalization for heart failure from emergency department on major adverse cardiovascular events in patients with and without type 2 diabetes.

BACKGROUND: Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes. METHODS: From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality. RESULTS: During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0-82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4-25.1] vs. 23.8 [21.3-26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0-80.7] mL/min/1.73 m2 vs. 69.2 [45.8-89.5] mL/min/1.73 m2) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04-5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86-2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26-5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81-2.16; compared to the reference group (group without T2DM or hypoglycemia). CONCLUSIONS: T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization.

External validation and clinical application of the predictive model for severe hypoglycemia.

Objective: An internally validated, one-year risk prediction model for severe hypoglycemia (SH) in type 2 diabetes was evaluated in a general hospital setting to externally verify and validate its performance. Research design and methods: Between December 2017 to December 2019, 2,645 adult patients with type 2 diabetes who visited the diabetes center were enrolled. The receiver operating characteristics curve and Harrell C-statistics were compared to identify the discrimination of the model. The predicted and actual incidence of SH for one year in the development and validation cohorts were compared by ranking participants by deciles of predicted risk. Results: The concordance index was 0.878 in the external validation cohort. The sensitivity and specificity of the predictive model were 0.833 and 0.847, respectively. Based on the predicted risk, we stratified the groups into four categories: low (<0.05%), intermediate (0.05% to <0.5%), high (0.5% to <2.0%), and very high-risk group (≥2.0%). The actual annual incidence of SH gradually increased with the increased risk score level for the decile group (P for trend <0.001). The actual annual SH incidence significantly increased with increase in SH risk scores, which proportionately increased with age, duration of diabetes, glycated hemoglobin, and albuminuria and decreased with body mass index, renal function (p for trends <0.001 for all) in type 2 diabetes. Conclusion: On external validation, the novel one-year SH prediction model showed excellent discrimination in participants with type 2 diabetes and can effectively screen high-risk patients for SH, even in the general hospital setting.

Efficacy of Personalized Diabetes Self-care Using an Electronic Medical Record-Integrated Mobile App in Patients With Type 2 Diabetes: 6-Month Randomized Controlled Trial.

BACKGROUND: A system that combines technology and web-based coaching can help treat chronic conditions such as diabetes. However, the effectiveness of apps in mobile health (mHealth) interventions is inconclusive and unclear due to heterogeneous interventions and varying follow-up durations. In addition, randomized controlled trial data are limited, and long-term follow-up is lacking, especially for apps integrated into electronic medical records. OBJECTIVE: We aimed to assess the effect of an electronic medical record-integrated mobile app for personalized diabetes self-care, focusing on the self-monitoring of blood glucose and lifestyle modifications, on glycemic control in patients with type 2 diabetes mellitus. METHODS: In a 26-week, 3-arm, randomized, controlled, open-label, parallel group trial, patients with type 2 diabetes mellitus and a hemoglobin A1c (HbA1c) level of ≥7.5% were recruited. The mHealth intervention consisted of self-monitoring of blood glucose with the automatic transfer of glucose, diet, and physical activity counseling data (iCareD system). Participants were randomly assigned to the following three groups: usual care (UC), mobile diabetes self-care (MC), and MC with personalized, bidirectional feedback from physicians (MPC). The primary outcome was the change in HbA1c levels at 26 weeks. In addition, diabetes-related self-efficacy, self-care activities, and satisfaction with the iCareD system were assessed after the intervention. RESULTS: A total of 269 participants were enrolled, and 234 patients (86.9%) remained in the study at 26 weeks. At 12 weeks after the intervention, the mean decline in HbA1c levels was significantly different among the 3 groups (UC vs MC vs MPC: -0.49% vs -0.86% vs -1.04%; P=.02). The HbA1c level decreased in all groups; however, it did not differ among groups after 26 weeks. In a subgroup analysis, HbA1c levels showed a statistically significant decrease after the intervention in the MPC group compared with the change in the UC or MC group, especially in patients aged <65 years (P=.02), patients with a diabetes duration of ≥10 years (P=.02), patients with a BMI of ≥25.0 kg/m2 (P=.004), patients with a C-peptide level of ≥0.6 ng/mL (P=.008), and patients who did not undergo treatment with insulin (P=.004) at 12 weeks. A total of 87.2% (137/157) of the participants were satisfied with the iCareD system. CONCLUSIONS: The mHealth intervention for diabetes self-care showed short-term efficacy in glycemic control, and the effect decreased over time. The participants were comfortable with using the iCareD system and exhibited high adherence. TRIAL REGISTRATION: Clinical Research Information Service, Republic of Korea KCT0004128; https://tinyurl.com/bdd6pa9m.

Association between lung function and the risk of atrial fibrillation in a nationwide population cohort study.

We investigated the association between lung function and atrial fibrillation (AF) in 21,349 adults without AF aged ≥ 40 years who underwent spirometry. The study participants were enrolled from the Korean National Health and Nutritional Examination Survey between 2008 and 2016. The primary outcome was new-onset non-valvular AF identified from the National Health Insurance Service database. During the median follow-up of 6.5 years, 2.15% of participants developed new-onset AF. The incidence rate of AF per 1000 person-years was inversely related to the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC quartile. After adjustment for multiple variables, the AF risk in the lowest FEV1 quartile was 1.64-fold higher than that in the highest quartile (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.26-2.12) for lowest FEV1 quartile). The lowest quartile of FVC had 1.56-fold higher AF risk than the highest quartile (HR 1.56 (95% CI 1.18-2.08) for lowest FVC quartile). Although the lowest FEV1/FVC quartile was associated with an increased risk of AF in the unadjusted model, this increased risk was not statistically significant in the multivariable analysis. Compared to those with normal lung function, participants with restrictive or obstructive lung function had 1.49 and 1.42-fold higher AF risks, respectively. In this large nationwide cohort study, both obstructive and restrictive patterns of reduced lung function were significantly associated with increased AF risk.

A deep learning model for screening type 2 diabetes from retinal photographs.

BACKGROUND AND AIMS: We aimed to develop and evaluate a non-invasive deep learning algorithm for screening type 2 diabetes in UK Biobank participants using retinal images. METHODS AND RESULTS: The deep learning model for prediction of type 2 diabetes was trained on retinal images from 50,077 UK Biobank participants and tested on 12,185 participants. We evaluated its performance in terms of predicting traditional risk factors (TRFs) and genetic risk for diabetes. Next, we compared the performance of three models in predicting type 2 diabetes using 1) an image-only deep learning algorithm, 2) TRFs, 3) the combination of the algorithm and TRFs. Assessing net reclassification improvement (NRI) allowed quantification of the improvement afforded by adding the algorithm to the TRF model. When predicting TRFs with the deep learning algorithm, the areas under the curve (AUCs) obtained with the validation set for age, sex, and HbA1c status were 0.931 (0.928-0.934), 0.933 (0.929-0.936), and 0.734 (0.715-0.752), respectively. When predicting type 2 diabetes, the AUC of the composite logistic model using non-invasive TRFs was 0.810 (0.790-0.830), and that for the deep learning model using only fundus images was 0.731 (0.707-0.756). Upon addition of TRFs to the deep learning algorithm, discriminative performance was improved to 0.844 (0.826-0.861). The addition of the algorithm to the TRFs model improved risk stratification with an overall NRI of 50.8%. CONCLUSION: Our results demonstrate that this deep learning algorithm can be a useful tool for stratifying individuals at high risk of type 2 diabetes in the general population.

Prevalence and clinical characteristics of fulminant type 1 diabetes mellitus in Korean adults: A multi-institutional joint research.

AIMS/INTRODUCTION: We aimed to determine the hospital-based prevalence and clinical features of fulminant type 1 diabetes mellitus in Korea. MATERIALS AND METHODS: We identified all patients with diabetes who regularly visited the Endocrinology outpatient clinics at eight centers for a period >1 year between January 2012 and June 2017. We investigated their medical records retrospectively. RESULTS: During this period, 76,309 patients with diabetes had been regularly followed up. Among them, 913 (1.2%) patients had type 1 diabetes mellitus . There were 462 patients with type 1 diabetes mellitus whose data at the time of the first diagnosis could be identified (359 and 103 with non-ketosis and ketosis onset, respectively). Of these, 15 (3.2% of type 1 diabetes mellitus, 14.6% of ketosis onset diabetes) patients had fulminant type 1 diabetes mellitus. The median ages at diagnosis were 40 and 27 years in the fulminant type 1 diabetes mellitus and non-fulminant type 1 diabetes mellitus groups, respectively. The patients with fulminant type 1 diabetes mellitus had higher body mass index, lower glycated hemoglobin and fasting/peak C-peptide, and lower frequent glutamic acid decarboxylase antibody-positive rate (P =0.0010) at diagnosis. Furthermore, they had lower glycated hemoglobin at the last follow-up examination than those with non-fulminant type 1 diabetes mellitus. CONCLUSIONS: In this study, the prevalence of type 1 diabetes mellitus was 1.2% among all patients with diabetes, and that of fulminant type 1 diabetes mellitus was 3.2% among those newly diagnosed with type 1 diabetes mellitus. The glycated hemoglobin levels were lower in patients with fulminant type 1 diabetes mellitus than in those with non-fulminant type 1 diabetes mellitus at diagnosis and at the last follow-up examination.

Personalized Type 2 Diabetes Management Using a Mobile Application Integrated with Electronic Medical Records: An Ongoing Randomized Controlled Trial.

Controlling type 2 diabetes (T2DM) requires a comprehensive approach including patient education, self-monitoring of blood glucose, individualized behavioral strategies, and frequent contact with healthcare professionals (HCPs). We aimed to compare the efficacy of a personalized lifestyle intervention based on a mobile phone application with regular care in participants with T2DM. This is an ongoing randomized controlled open-label parallel-group trial with a target accrual of 282 participants, of which 181 have been enrolled to date. Participants are randomly assigned to one of three groups: (1) regular care; (2) mobile diabetes management; or (3) mobile diabetes management with HCP feedback. The mobile application is enabled to integrate with both electronic medical records (EMR) and a web-based diabetes management system for HCPs. It can send customized messages based on participants' responses to lifestyle questionnaires administered at the baseline. The intervention period is 26 weeks followed by observation for 26 weeks. We evaluate the intervention's features in order to assess its clinical utility and efficacy and compare outcomes with regular care considering relevant clinical factors, such as age, baseline HbA1c, etc. We expect our study to provide new evidence in support of customized mobile application tools for the management of T2DM.

Association between toothbrushing and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Periodontitis, as chronic inflammatory destructive disease, is associated metabolic syndromes bidirectionally. Toothbrushing is an essential and important way to manage periodontitis through mechanical removal of biofilm at periodontal tissue. We aimed to assess the association between toothbrushing frequency and the prevalent NAFLD in nationally representative Korean adults. Among adults aged 19 years and older who participated in the Korea National Health and Nutrition Examination Survey in 2010, a total of 6,352 subjects were analyzed. NAFLD was defined as fatty liver index ≥60. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). An inverse association between toothbrushing frequency and NAFLD was found. The adjusted ORs (95% CIs) of NALFD was 0.56 (0.35-0.91) in the group who performed toothbrushing ≥ 3 per day compared to the group that performed toothbrushing ≤ 1 per day. For those with toothbrushing frequency ≤1 per day, the adjusted OR (95% CIs) of NAFLD was 2.26 (1.22-4.19) in smokers and 4.52 (1.97-10.38) in subjects with diabetes mellitus (DM), compared to those without the disease and with toothbrushing frequency ≥2 per day, respectively. Our results indicate that higher frequency of toothbrushing is inversely associated with NAFLD. As a modifiable oral habit, regular toothbrushing may be recommended to lower risk of NAFLD, especially in high risk groups such as smokers and diabetic patients.

Severe hypoglycemia and the risk of end stage renal disease in type 2 diabetes.

We investigated the association between the incidence of severe hypoglycemia and the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes. Baseline and follow-up data for 988,333 participants with type 2 diabetes were retrieved from the National Health Insurance System database. The number of severe hypoglycemia episodes experienced from 2007 to 2009 was determined. The primary outcome was the development of ESRD after the baseline evaluation. Participants were followed from the baseline until death or December 31, 2016, during this period 14,545 participants (1.5%) developed ESRD. In the crude model, compared with those who experienced no severe hypoglycemia, the hazard ratios (95% confidential intervals) for developing ESRD were 4.96 (4.57-5.39), 6.84 (5.62-8.32), and 9.51 (7.14-12.66) in participants who experienced one, two, and three or more episodes of severe hypoglycemia, respectively. Further adjustment for various confounding factors attenuated the association between severe hypoglycemia and ESRD; the significance of the association between severe hypoglycemia and ESRD was maintained. Having three or more severe hypoglycemia episodes was associated with a nearly two-fold increased risk of developing ESRD. Prior episodes of severe hypoglycemia were associated with an increased risk of ESRD among Korean adults with type 2 diabetes.

Impaired fasting glucose levels in overweight or obese subjects for screening of type 2 diabetes in Korea.

BACKGROUND/AIMS: We examined the concordance rate among fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hr PG), and hemoglobin A1c (HbA1c) in the diagnosis of diabetes in a population with a high-risk for type 2 diabetes mellitus (T2DM) in Korea. METHODS: Among the participants from the Korean Diabetes Prevention Study, individuals with FPG ≥ 100 mg/dL, body mass index (BMI) ≥ 23.0 kg/m2, and no previous history of T2DM were consecutively enrolled after a 75 g glucose tolerance test. We analyzed the differences in the clinical characteristics in subjects with stage 1 (FPG, 100 to 109 mg/dL) and stage 2 (FPG, 110 to 125 mg/dL) impaired fasting glucose (IFG). RESULTS: Of 1,637 participants, 27.2% had T2DM and 59.3% had IFG and/or impaired glucose tolerance (IGT). The mean age was 55.0 ± 8.1 years and the mean BMI was 26.3 ± 2.7 kg/m2. Based on FPG criteria, 515 (31.4%) and 352 (21.5%) subjects were classified as having stage 1 and stage 2 IFG, respectively. The 19.0% of stage 1 and 43.5% of stage 2 subjects showed 2hr PG levels in the diabetic range. Even for those in the normal FPG range, 63 (9.5%) participants showed a 2hr PG level of ≥ 200 mg/dL. Of 446 subjects with newly-diagnosed diabetes, 340 (76.2%) showed FPG levels < 126 mg/dL. CONCLUSION: The oral glucose tolerance test should be actively considered for Korean adults who are overweight or obese with the IFG range (FPG, 100 to 125 mg/ dL) to allow for early detection of diabetes and prompt intervention.

Associations of general obesity and central obesity with the risk of hepatocellular carcinoma in a Korean population: A national population-based cohort study.

Numerous previous studies have shown an association between general obesity and hepatocellular carcinoma (HCC). However, relatively few reports on the association of central obesity and HCC are available in Asian populations. Therefore, we investigated the association between WC representing central obesity and the risk of HCC in addition to BMI representing general obesity and the risk of HCC in Korea. A total of 10 505 818 participants who received the National Health Insurance Service (NHIS) health checkups in 2009 were screened for study eligibility, and 26 979 cases of HCC occurred during the 7.3 years of mean follow-up. General obesity increased the risk of HCC with hazard ratios (HRs) of 1.14 (95% CI, 1.11-1.18) for BMI 25.0-<30.0 kg/m2 and 1.52 (95% CI, 1.43-1.61) for BMI ≥30 kg/m2 compared to those whose BMI is within the normal range. Central obesity was also associated with a higher risk of HCC. For the participants with a WC ≥105 cm in men and WC ≥100 cm in women, the risk of HCC was higher than that of the reference group (HR = 1.69, 95% CI, 1.54-1.85). The HRs were 1.13 (95% CI, 1.07-1.19) for nonobese participants with central obesity, and 1.34 (95% CI, 1.30-1.38) for obese participants with central obesity compared to those without both conditions. Our findings suggest that the risk of HCC increases even more when general obesity is combined with central obesity. Moreover, central obesity is associated with the risk of HCC, regardless of general obesity.

Fasting glucose level and all-cause or cause-specific mortality in Korean adults: a nationwide cohort study.

BACKGROUND/AIMS: Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting glucose (FG) levels and cause-specific mortality rates in the general population. METHODS: A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. RESULTS: During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FG levels was increased for men but not women. CONCLUSION: The risk of all-cause and cause-specific mortality showed the tendency to increase when the FG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.

Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic ß-cells.

Islet transplantation (ITx) is being developed as a treatment for type 1 diabetes mellitus, but hypoxic damage to transplanted islet grafts is an important factor affecting successful transplantation. To investigate the role of sirtuin-1 (SIRT1) under hypoxic injury in INS-1 cells, one type of pancreatic ß-cell lines, we used SRT1720 and GW4064 for SIRT1 activation. The small interfering RNA SIRT1 (si-SIRT1) was used to suppress SIRT1 gene expression. We measured cell viability, apoptosis, and the levels of inflammatory cytokines, including tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS), under hypoxic conditions. Real-time PCR and Western blot analysis were performed. Cell viability was significantly reduced to 71% and 40% after 4 and 6 h of hypoxic conditions, respectively. Apoptosis increased significantly 2.8-fold and 5.3-fold after 4 and 6 h of hypoxia, respectively. SIRT1 expression was significantly reduced at the mRNA and protein levels during hypoxia. Hypoxic damage significantly increased the TNF-α, IL-6 and ROS levels in INS-1 cells. However, the reduced cell viability and increased inflammatory cytokines from hypoxic damage were ameliorated by SIRT1 activation in INS-1 cells. These results suggest that SIRT1 is a potential target for the protection of pancreatic ß-cells against hypoxic damage during ITx.

Hypoxia Increases ß-Cell Death by Activating Pancreatic Stellate Cells within the Islet.

BACKGROUND: Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing ß-cell injury. METHODS: Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia. RESULTS: Islets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis. CONCLUSION: PSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to ß-cell loss in type 2 diabetes mellitus.