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Determine whether the twice daily (BID) regimen is superior to the once daily (QD) regimen for managing glycemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD.A double-blinded, randomized, multicenter study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5%HbA1c 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring (CGM) was used to measure the mean amplitude of glycemic excursion (MAGE) and postprandial time in range (TIR) before and after DPP-4 inhibitor treatment to compare glycemic variability.The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (p0.05); -30.4 ± 25.6 mg/dL (p0.001) in the anagliptin group versus -9.5 ± 38.0 mg/dL (p=0.215) in the sitagliptin group. The TIR after dinner increased by 33.0 ± 22.0% (p0.001) in the anagliptin group and by 14.6 ± 28.2% (p=0.014) in the sitagliptin group, with a statistically significant difference (p=0.009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG).The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycemic variability, as indicated by MAGE and TIR but equivalent to the QD regimen in terms of HbA1c and FPG. This article is protected by copyright. All rights reserved.

Background: On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes.Methods: Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured.Results: In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P

Background: The effect of intrauterine hyperglycemia on fat mass and regional fat proportion of the offspring of mothers with gestational diabetes mellitus (OGDM) remains to be determined.Methods: The body composition of OGDM (n=25) and offspring of normoglycemic mothers (n=49) was compared using dualenergy X-ray absorptiometry at age 5 years. The relationship between maternal glucose concentration during a 100 g oral glucose tolerance test (OGTT) and regional fat mass or proportion was analyzed after adjusting for maternal prepregnancy body mass index (BMI).Results: BMI was comparable between OGDM and control (median, 16.0 kg/m2 vs. 16.1 kg/m2 ). Total, truncal, and leg fat mass were higher in OGDM compared with control (3,769 g vs. 2,245 g, P=0.004; 1,289 g vs. 870 g, P=0.017; 1,638 g vs. 961 g, P=0.002, respectively), whereas total lean mass was lower in OGDM (15,688 g vs. 16,941 g, P=0.001). Among OGDM, total and truncal fat mass were correlated with fasting and 3-hour glucose concentrations of maternal 100 g OGTT during pregnancy (total fat mass, r=0.49, P=0.018 [fasting], r=0.473, P=0.023 [3-hour]; truncal fat mass, r=0.571, P=0.004 [fasting], r=0.558, P=0.006 [3-hour]), but there was no correlation between OGDM leg fat mass and maternal OGTT during pregnancy. Regional fat indices were not correlated with concurrent maternal 75 g OGTT values.Conclusion: Intrauterine hyperglycemia is associated with increased fat mass, especially truncal fat, in OGDM aged 5 years.

Aims/Introduction The benefits of once‐daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. Materials and Methods This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once‐daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. Results The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C‐peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P, Once‐daily insulin degludec/aspart was more effective in glycated hemoglobin reduction than basal insulin, especially in patients showing a lower ratio of fasting plasma glucose‐to‐estimated average glucose. This indicates that marked postprandial hyperglycemia was tied to the efficacy of once‐daily insulin degludec/aspart compared with basal insulin.

Objective: Ischemia in pancreatic islets is critical to beta cell function, however, clinical evidences on the implications for diabetes are lacking. Pancreatectomy can induce diabetes, but the mechanisms are not clearly elucidated. Therefore, we examined if cardiovascular disease (CVD) risk factors and intraoperative ischemia, which could cause perfusion insufficiency in pancreatic islets, are associated with insulin deficiency and diabetes after pancreatectomy. Methods: From 2 prospective cohorts of pancreatectomy since 2007, participants were enrolled who had pre-operative HbA1c < 7% without antidiabetes. As for proximal pancreatectomy, those were selected whose HOMA-R increased after surgery. Insulin secretion was assessed by changes in HOMA-B for 1 year (ΔB) . The participants were divided into low- and high-ΔB groups, with stratification by operation type, pre-operative HbA1c, HOMA-B, HOMA-R, and ΔR. Then CVD risk factors and intraoperative ischemic events were compared between the 2 groups, and evaluated for diabetes incidence. Results: A total of 237 patients were enrolled (men 44%, age 56 years, HbA1c 5.6% in average) . Low-ΔB (median -32% of baseline) and high-ΔB (5%) groups showed comparable baseline metabolic variables. According to logistic regression analyses and Cox regression model, a composite of IGT, hypertension, dyslipidemia and a reduction in intraoperative systolic BP significantly decreased HOMA-B after 1 year (RR, 9.52; 95% CI, 1.14-79.3) , and increased diabetes incidence (HR, 3.3; 95% CI, 1.2-8.9) , after adjustment with age, sex, BMI, HbA1c and operation. Conclusion: We observed that chronic ischemia suggested by CVD risk factors and intraoperative ischemic insult were linked to development of insulin deficiency and diabetes after pancreatectomy. Disclosure S.Moon: None. K.Park: None. H.Jang: None. J.Jang: None. H.Jung: Advisory Panel; Novo Nordisk, Research Support; Jeil Pharmaceutical Co., Novo Nordisk. J.Lee: None. H.Sohn: None. Y.Han: None. H.Kim: None. W.Kwon: None. Y.Yoon: None. H.Han: None. T.Oh: None. Funding National Research Foundation of Korea (2019R1A2C1007397)

Around 30-50% of women with history of gestational diabetes (GDM) develop type 2 diabetes (T2D) within years after parturition. However, the role of polygenetic score on prediction of T2D in these women is still unclear. We aimed to investigate the utility of global extended polygenic scores (gePS) in predicting incident T2D using GDM cohorts from 1) UK Biobank (N=941) , 2) Seoul National University Hospital (SNUH, N=357) , and 3) Korean Genome and Epidemiology Study (KoGES, N=379) . We calculated gePS for T2D using Bayesian regression and continuous shrinkage priors, with summary statistics from representative genome-wide association studies in Europeans and East Asians. We performed time-to-event analysis for incident T2D with gePS and assessed improvement of C-statistic when gePS was added to clinical risk factors. In addition, risk of T2D was estimated for those who were in the top percentile of gePS compared to the remainders. The incidence of T2D was 19.8% in UK Biobank, 28.3% in SNUH, and 23.5% in KoGES cohort with median follow-up duration of 28, 4, and 28 years, respectively. The normalized mean PRS for those who developed T2D was higher in each cohort: 0.25±1.vs. -0.06±0.99 in UK Biobank, 0.22±1.vs. -0.09±0.97 in SNUH, and 0.52±0.96 vs. -0.16±0.96 in KoGES (all P Disclosure J.Choi: None. H.Lee: None. M.Han: None. D.Choi: None. H.Jang: None. K.Park: None. S.Kwak: None.

Background The influence of serial changes of adipokines on maternal glucose metabolism from pregnancy to postpartum periods in women with previous gestational diabetes mellitus (pGDM) has not been thoroughly explored. We tried to examine the relationship between the serial changes of adipokines and the development of diabetes mellitus (DM) in women with pGDM. Methods We longitudinally measured following adipokines: high molecular weight (HMW) adiponectin, retinol-binding protein-4 (RBP-4), lipocalin-2, and chemerin, during pregnancy, and at 2 months and 3 years after delivery. Based on glucose status at postpartum 3 years, we divided into three groups: normal glucose tolerance (GDM-NGT, n=20), impaired glucose tolerance (GDM-IGT, n=23), and GDM-DM (n=22). We analyzed the correlations between adipokines and various metabolic parameters. Results Plasma HMW adiponectin levels were not different among the three groups during pregnancy. However, HMW adiponectin levels increased at 3 years after the delivery in women with GDM-NGT compared with women with GDM-DM. In the GDM-IGT group, HMW adiponectin levels increased at 2 months postpartum compared to pregnancy period. In contrast, HMW adiponectin levels showed no alternation after parturition in women with GDM-DM. HMW adiponectin was negatively correlated with body mass index and a homeostasis model assessment of insulin resistance. Other adipokines such as RBP-4, lipocalin-2, and chemerin neither showed any differences among the groups nor any significant correlations with 3 years postpartum status of glucose intolerance. Conclusion Serial changes of HMW adiponectin are associated with the maintenance of glucose metabolism in women with pGDM after delivery.

Background While aging causes muscle weakness, type 2 diabetes mellitus (T2DM) is also considered a high-risk factor for the induction of skeletal muscle weakness. Previous studies have reported increased collagen content in insulin-resistant skeletal muscles. Here, we studied the mechanical properties of aged skeletal muscle in subjects with T2DM to investigate whether aged skeletal muscles with T2DM induce higher passive tension due to the abundance of extracellular matrix (ECM) inside or outside of the muscle fibers. Methods Samples from the gluteus maximus muscles of older adults with diabetes (T2DM) and non-diabetic (non-DM) older adults who underwent elective orthopedic surgery were collected. Permeabilized single muscle fibers from these samples were used to identify their mechanical properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to quantify titin and fiber type distributions in these samples. Results We confirmed a significant predominance of type I fiber ratio in both T2DM and non-DM aged muscles. While the average cross-sectional area and maximal active tension of the single fibers were smaller in the T2DM group than those in the non-DM group, the difference was not statistically significant. T2DM subjects showed significantly greater passive tension and lower titin-/ECM-based passive tension ratios than those in non-DM subjects, which indicated that more ECM but less titin contributed to the total passive tension. Conclusion Based on our findings, we concluded that T2DM may cause increased passive stiffness of single skeletal muscle fibers in older adults because of an excessive accumulation of ECM in and around single muscle fibers due to increased insulin resistance.

Aims/Introduction We developed a self‐assessable Korean Diabetes Risk score using the data of the Korean Genome and Epidemiology Study. Materials and Methods A total of 8,740 participants without diabetes at baseline were followed up biannually over a period of 10 years. We included variables that were significantly different between participants who developed diabetes mellitus and those who did not in the development cohort at baseline. We assigned a maximum score of 100 to the selected variable in each gender group. Next, the 10‐year probability of incident diabetes was calculated and validated in the validation cohort. Finally, we compared the predictive power of Korean Diabetes Risk score with models including fasting plasma glucose or glycated hemoglobin and other cohort models of Atherosclerosis Risk in Communities and Korea National Health and Nutrition Examination Survey. Results During a median follow‐up period of 9.7 years, 22.7% of the participants progressed to diabetes. The Korean Diabetes Risk score included age, living location (urban or rural area), waist circumference, hypertension, family history of diabetes and smoking history. The developed risk score yielded acceptable discrimination for incident diabetes (area under the curve 0.657) and the predictive power was improved when the model included fasting plasma glucose (area under the curve 0.690) or glycated hemoglobin (area under the curve 0.746). In addition, our model predicted incident diabetes more accurately than previous Western or Korean models. Conclusions This newly developed self‐assessable diabetes risk score is easily applicable to predict the future risk of diabetes even without the necessity for laboratory tests. This score is useful for the Korean diabetes prevention program, because high‐risk individuals can be easily screened., Age, living location (rural or urban), smoking, hypertension, family history of type 2 diabetes and waist circumference were key risk factors of new‐onset type 2 diabetes in Korean individuals. A self‐assessable Korean Diabetes Risk score composed with non‐laboratory variables provided better accurate prediction of 10‐year risk of new‐onset type 2 diabetes compared with a Western study or a previously developed Korean Diabetes Score.

Aim To evaluate the pharmacokinetic and pharmacodynamic properties of a novel glycosylated Fc‐fused glucagon‐like peptide‐1(GLP‐1‐gFc) receptor agonist with distinctive receptor binding affinity, designed to improve in vivo stability and safety relative to the commercial GLP‐1 analogue dulaglutide, and assess its safety profile and pharmacokinetics in healthy humans. Materials and Methods We constructed GLP‐1‐gFc and determined its binding affinity and potency using in vitro instrumental and cell‐based analyses followed by in vivo comparison of the glucose‐lowering and gastrointestinal side effects between GLP‐1‐gFc and dulaglutide. A phase 1 clinical trial was conducted to confirm the efficacy and safety profile of GLP‐1‐gFc. Results GLP‐1‐gFc showed 10‐fold less binding affinity and 4‐fold less potency than dulaglutide in in vitro. A potency‐adjusted dose delayed HbA1c increase comparable with that of dulaglutide (Change for 6 weeks: 2.4 mg/kg GLP‐1‐gFc, 4.34 ± 0.40 vs. 0.6 mg/kg dulaglutide, 4.26 ± 0.22; n.s.). However, the equivalent efficacy dose and higher dose did not induce malaise‐related responses (blueberry bar consumption, g/mouse: 2.4 mg/kg GLP‐1‐gFc, 0.15% ± 0.03% vs. 0.6 mg/kg dulaglutide, 0.04% ± 0.01%; P

Depressive mood consequent to hypothyroidism can be reversed with levothyroxine (LT4) replacement therapy. However, it is unclear whether increasing LT4 dose confers additional mood benefits.A single-blinded before-and-after study of 24 patients with hypothyroidism who were aged 65 years or older and undergoing LT4 replacement therapy with stable doses.Geriatric Depression Scale (GDS-K) and Hyperthyroid Symptom Scale (HSS-K) were assessed at baseline, 3 months after increasing LT4 dose by an additional 12.5 µg/d, and finally 3 months after returning to the baseline dose.Serum thyroid-stimulating hormone (TSH) concentrations decreased at the higher LT4 dose (1.95 ± 2.16 vs 0.47 ± 1.09 mIU/L, P .001) and recovered after returning to the baseline dose. Serum-free thyroxine levels and HSS-K scores were unchanged during the study period. GDS-K scores improved on the increased dose (9.5 ± 6.6 vs 7.5 ± 4.7, P = .029), and this improvement was maintained after returning to the baseline dose (9.5 ± 6.6 vs 7.4 ± 5.4, P = .010). Higher serum TSH was independently associated with both higher GDS-K and depression risk among those with depressive mood (GDS-K 10) at baseline.Depressive mood improves with increased LT4 dose, without significant hyperthyroid symptoms or signs, in older adults undergoing thyroid hormone replacement. These findings suggest the potential for varying the treatment target for hypothyroidism based on mood status and that low-dose LT4 treatment might be an ancillary treatment for depression.

OBJECTIVE To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen. RESEARCH DESIGN AND METHODS This multicenter, double-blind, treat-to-target trial randomized participants to faster aspart (n = 546) or IAsp (n = 545). All available information, regardless of treatment discontinuation or use of ancillary treatment, was used for evaluation of effect. RESULTS Noninferiority for the change from baseline in HbA1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] −0.04% [95% CI −0.11; 0.03]; −0.39 mmol/mol [−1.15; 0.37]; P < 0.001). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD −0.40 mmol/L [−0.66; −0.14]; −7.23 mg/dL [−11.92; −2.55]; P = 0.001 for superiority). Change from baseline in self-measured 1-h PPG increment for the mean over all meals favored faster aspart (ETD −0.25 mmol/L [−0.42; −0.09]); −4.58 mg/dL [−7.59; −1.57]; P = 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)–confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio 0.81 [95% CI 0.68; 0.97]). CONCLUSIONS In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

Background This study explored the prevalence and clinical characteristics of geriatric syndromes among Korean older adults with diabetes mellitus (DM). Methods We used data from the 2017 National Survey of Older Koreans to analyze the classic geriatric syndromes of polypharmacy, urinary incontinence, falls, cognitive impairment, and functional impairment according to the presence of DM. Results Among 10,299 participants aged 65 years or older, 2,395 had DM. The prevalence of polypharmacy was 64.1% in the DM group and 31.6% in the non-DM group (p

Background/Aims: Depression and allergic diseases, including asthma, are frequently reported as comorbid conditions. However, their associations have been rarely examined in community-based elderly populations. Methods: The analyses were performed using the baseline data set of the Korean Longitudinal Study of Health and Aging, which consists of 1,000 elderly participants (aged > 65 years) randomly recruited from an urban community. Depression was assessed using the Geriatric Depression Scale, Center for Epidemiologic Studies Depression Scale, and Hamilton Rating Scale for Depression. Major and minor depressive disorders were diagnosed by psychiatrists. Allergic conditions were assessed using structured questionnaires, lung function, and skin prick test. Quality of life and comorbidities were assessed using structured questionnaires. Results: Prevalence of asthma and major depressive disorder were 5.4% and 5.3%, respectively. The rate of depression was not significantly different between the non-asthmatic and asthmatic groups. No correlation was observed between the scores obtained using the depression scales and self-reported asthma. However, chronic, frequent, and nocturnal cough were significantly associated with depression and scores obtained using the depression scales, which remained significant in multivariate logistic regression analyses (chronic cough: odds ratio [OR], 3.23; 95% confidence interval [CI], 2.57 to 12.74; p = 0.04). Rhinitis was independently associated with high Mini-Mental State Examination scores (OR, 1.11; 95% CI, 1.05 to 1.17; p < 0.001) and low 36-item short-form (OR, 0.96; 95% CI, 0.80 to 0.98; p = 0.002). Conclusions: Depression may not be significantly associated with asthma and allergic diseases in elderly populations, but cough is a significant factor affecting depression.

Hye Soon Kim,1 Jae Myung Yu,2 Hak Chul Jang,3 Eui Kwang Choi,4 Jeong Hyun Park,5 Ho Sang Shon,6 Choon Hee Chung,7 Keun-Gyu Park,8 Jae Hyoung Cho,9 Won Kim,10 Kyoung Hwa Lee,10 Jee Hyun Lee,10 Soon Jib Yoo11 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Department of Internal Medicine, Naedang Dr. Choi’s Clinic, Seoul, Republic of Korea; 5Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; 6Department of Internal Medicine, Catholic University of Daegu, School of Medicine, Daegu, Republic of Korea; 7Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; 8Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 9Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 10Medical Department Sanofi-Aventis Korea, Seoul, Republic of Korea; 11Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of KoreaCorrespondence: Soon Jib Yoo, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 14647, Republic of Korea, Tel +82-32-340-7011, Fax +82-32-340-2039, Email sjyoomt@gmail.comPurpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This non-interventional, observational study enrolled patients (aged > 18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months.Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; − 1.16± 6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: − 54.9± 90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: − 89.46± 105.68 mg/dl, p< 0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45± 3.64 kg, p< 0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥ 2 RAI injections/day) had HbA1c < 7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p< 0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥ 2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: − 1.27± 1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: − 0.72± 1.66%) (p=0.0459), without a significant increase in BW and body mass index.Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.Keywords: glycated hemoglobin, insulin glulisine, intensification, RAI analogs

Context Nonalcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis are related to higher mortality. Objective We investigated whether noninvasive indices of NAFLD and liver fibrosis could predict mortality in a Korean prospective cohort study. Methods We followed 4163 subjects from the Korean Genome and Epidemiology Study biannually over 16 years. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) of NAFLD or liver fibrosis indices in the total group of subjects and subgroups according to body mass index (BMI) and glucose metabolism status. Results The mean age (± SD) of the subjects was 55.7 ± 8.7 years and 39.2% were men. During a median follow-up period of 15.6 years, 643 subjects (15.4%) died. The Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index were consistently higher in deceased subjects regardless of baseline glucose metabolism status. The FIB-4 and NFS displayed acceptable discrimination power for mortality, with area under the receiver operating characteristic curve values of 0.686 and 0.666, respectively. The adjusted HRs for FIB-4 and NFS were 1.41 (95% CI, 1.18-1.68) and 1.43 (95% CI, 1.21-1.68), respectively. Both FIB-4 and NFS were significantly associated with liver-specific mortality but not cardiovascular mortality. The association between mortality with fibrosis indices were more prominent in subjects with a lower BMI ( Conclusion Noninvasive indices of liver fibrosis might be a significant predictor of all-cause and liver-specific mortality in Korean subjects.

Despite the association between sarcopenia and non-alcoholic fatty liver disease (NAFLD), no study has evaluated the predictive role of NAFLD in sarcopenia. We investigated impact of NAFLD on the risk of low muscle mass (LMM) and low muscle strength (LMS) in a nationwide multicenter study. A total of 1595 community-dwelling people aged 70–84 years were followed for 2 years in the Korean Frailty and Aging Cohort Study. Muscle mass was estimated by dividing appendicular skeletal muscle mass (ASM) by body mass index (BMI). Muscle strength was measured as handgrip strength (HGS) divided by BMI. The sex-specific lowest quintiles of ASM/BMI and HGS/BMI of the study population were used as cutoffs for LMM and LMS, respectively. The risk of LMM and LMS were assessed according to hepatic steatosis index (HSI) and fatty liver index (FLI) quartiles. As HSI quartiles increased, the LMM risk increased gradually, after adjusting for age, sex, lifestyle factors, comorbidities, and several causative factors (insulin resistance, inflammation, and vitamin D) (Q4 vs. Q1 OR [95% CI] 3.46 [2.23–5.35]). The increased risk of LMS was even higher according to HSI quartiles (Q4 vs. Q1 5.81 [3.67–9.21]). Multivariate analyses based on FLI showed similar results. People with NAFLD (HSI > 36) were at higher risk of developing LMM and LMS compared to those without (1.65 [1.19–2.31] and 2.29 [1.61–3.26], respectively). The presence of NAFLD may predict future risk of LMM and LMS, with greater impact on LMS than on LMM.

Background: Obesity is an important risk factor for polyneuropathy (PN) in subjects with DM. However, PN can be detected in subjects without overt DM but with risk factors for DM such as metabolic syndrome. Therefore, it is worthy to investigate the prevalence of PN in obese subjects and to discover the underlying mechanisms of the association between obesity and PN. Methods: We analyzed the data of 184 subjects who underwent bariatric/metabolic surgery. PN was diagnosed when a Michigan Neuropathy Screening Instrument score was ≥ 2.5. Total body fat mass and percentage were measured by bioimpedance analysis, and visceral fat area (VFA) was quantified by computed tomography. According to DM status, obesity-related parameters were compared between subjects with PN and those without PN. The association between obesity-related parameters and PN was analyzed using logistic regression models. Results: Of 184 subjects (mean age, 39.1 years; mean BMI, 38.6 kg/m2), 39.7% were diagnosed with DM. The prevalence of PN was 9.0% in non-DM group and 21.9% in DM group. In non-DM group, subjects with PN showed higher HOMA-IR, fat mass, and VFA compared with those without PN. HOMA-IR (OR, 1.492; 95% CI, 1.110-2.005), fat mass (OR, 1.087; 95% CI, 1.008-1.171), and VFA (OR 1.013; 95% 1.001-1.024) were significantly associated with PN even after adjustment of known risk factors of PN. In DM group, subjects with PN showed higher body weight, BMI, waist circumference, and VFA compared with those without PN. However, after adjustment of known risk factors of PN, these obesity related parameters were not significantly associated with PN. Conclusion: Fat mass and insulin resistance might be independent risk factors in development of PN for obese subjects without DM. PN evaluation might be necessary in subjects with morbid obesity even before development of overt DM, and we need to investigate whether weight loss intervention can prevent or delay PN in obese subjects. Disclosure K. Kim: None. T. Oh: None. S. Choi: None. H. Jang: None.

Background : Previous epidemiologic studies showed that obesity increased the risk of diabetic peripheral neuropathy (DPN). However, there is very limited data about the impact of body fat measured by body composition analysis in DPN. Methods : Subjects with type 2 diabetes mellitus (T2DM) between 20 to 55 years old were enrolled. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Body composition was assessed by bio-impedance analysis, and the association between body composition and DPN was investigated. Results : Among 65 subjects, 44.6% were diagnosed with DPN. Subjects with DPN had higher body mass index and waist circumference than subjects without DPN. Body composition data showed that fat mass, fat percent, and visceral fat area were higher in subjects with DPN than in subjects without DPN. Furthermore, the presence of DPN was associated with waist circumference (odds ratio [OR], 1.151; 95% confidence interval [CI], 1.055-1.256; P=0.002), visceral fat area (OR, 1.026; 95% CI, 1.005-1.048; P=0.015), and insulin resistance (OR, 1.673; 95% CI, 1.091-2.565; P=0.018) after adjusting age, sex, diabetes duration, and smoking status. Conclusion : Abdominal obesity was associated with DPN. Insulin resistance might mediate obesity and DPN in middle aged subjects with T2DM.

Background We aimed to identify the postpartum metabolic factors that were associated with the development of diabetes in women with a history of gestational diabetes mellitus (GDM). In addition, we examined the role of the oral glucose tolerance test (OGTT) in the prediction of future diabetes. Methods We conducted a prospective study of 179 subjects who previously had GDM but did not have diabetes at 2 months postpartum. The initial postpartum examination including a 75-g OGTT and the frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed 12 months after delivery, and annual follow-up visits were made thereafter. Results The insulinogenic index (IGI30) obtained from the OGTT was significantly correlated with the acute insulin response to glucose (AIRg) obtained from the FSIVGTT. The disposition indices obtained from the OGTT and FSIVGTT were also significantly correlated. Women who progressed to diabetes had a lower insulin secretory capacity including IGI30, AIRg, and disposition indices obtained from the FSIVGTT and OGTT compared with those who did not. However, the insulin sensitivity indices obtained from the OGTT and FSIVGTT did not differ between the two groups. Multivariate logistic regression analysis showed that the 2-hour glucose and disposition index obtained from the FSIVGTT were significant postpartum metabolic risk factors for the development of diabetes. Conclusion We identified a crucial role of β-cell dysfunction in the development of diabetes in Korean women with previous GDM. The 2-hour glucose result from the OGTT is an independent predictor of future diabetes. Therefore, the OGTT is crucial for better prediction of future diabetes in Korean women with previous GDM.

Aim To perform a prospective study to evaluate the effect of cilostazol (CTZ) compared with aspirin (acetylsalicylic acid; ASA) in Korean people with diabetes and subclinical coronary atherosclerosis. Materials and methods A total of 100 people with diabetes who had mild to moderate coronary atherosclerosis, assessed by coronary computed tomographic angiography (CCTA), were randomly assigned to either 200 mg/d CTZ or 100 mg/d ASA (n = 50 each group). The primary outcome was change in coronary artery stenosis assessed by CCTA after 12 months of treatment. Secondary outcomes included changes in plaque composition, coronary artery calcium score and cardiac markers. Results The mean age, body mass index and glycated haemoglobin concentration were 61.5 years, 25.0 kg/m2 and 56.8 mmol/mol, respectively, and were well matched between the two groups. Coronary artery stenosis decreased in the CTZ group (from 44.0 ± 2.1% to 40.4 ± 2.5%) but remained unchanged in the ASA group (from 38.9 ± 2.1% to 40.6 ± 2.1%). In the CTZ group, the non-calcified portion of plaques decreased significantly (from 20.6 ± 3.0 to 17.3 ± 3.0 mm3 ), whereas it did not change significantly in the ASA group (15.2 ± 2.8 vs 16.6 ± 2.9 mm3 ). Increases in HDL cholesterol, decreases in triglycerides, liver enzyme and high-sensitivity C-reactive protein levels, and reductions in abdominal visceral fat area and insulin resistance were observed only in the CTZ group. Conclusion CTZ treatment for 12 months decreased coronary artery stenosis and the non-calcified plaque component. These results suggest that CTZ treatment may be an option for preventing the progression of coronary atherosclerosis in people with diabetes.

Context Body-weight fluctuation (weight cycling) has been found to be associated with higher mortality and cardiovascular events in patients with coronary artery disease. However, there are very limited data regarding the relationship between body-weight fluctuation and health-related outcomes in the general population. Methods We examined whether body-weight fluctuation can associate incident diabetes mellitus and cardiovascular events, and mortality in a Korean population from the Korean Genome and Epidemiology Study. The intraindividual fluctuations of body weight were calculated by average successive variability (ASV); health-related outcomes were collected every 2 years for 16 years in 3,678 participants. Results Participants with a high ASV of body weight were more obese and had higher blood pressure and HbA1c levels at baseline than those with a low ASV of body weight. A 1-unit increase in ASV of body weight was associated with increase in mortality (HR, 1.46; 95% CI, 1.32 to 1.62; P < 0.001). However, the association between the ASV of body weight and incident diabetes mellitus seemed to be influenced by baseline body mass index (BMI): negative effect in subjects with BMI Conclusion Body-weight fluctuation was associated with mortality. In addition, the effect of body-weight fluctuation on incident diabetes mellitus depended on the presence of obesity at baseline.

Context Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available. Objective This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA. Methods This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT). Results In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type–linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case. Conclusion We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.

We aimed to investigate the association of iron and polyunsaturated fatty acid (PUFA) intake with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes. This cross-sectional study included 147 individuals with type 2 diabetes. Dietary intake was assessed using three-day food records. DPN was diagnosed on the basis of a Michigan Neuropathy Screening Instrument&mdash, Physical Examination score &ge, 2.5. Adjusted for total energy intake, iron intake was significantly higher in individuals with DPN than in those without DPN (10.9 &plusmn, 4.0 mg vs. 9.9 &plusmn, 3.6 mg, p = 0.041). In addition, the iron/PUFA ratio was significantly higher in individuals with DPN (1.4 &plusmn, 0.8 vs. 1.1 &plusmn, 0.4, p = 0.005). Logistic regression analyses showed that iron intake (odds ratio (OR): 1.152, 95% confidence interval (CI): 1.012, 1.311) and iron/PUFA ratio (OR: 2.283, 95% CI: 1.066, 4.887) were associated with DPN after adjustment for total energy intake, sex, age, body mass index, systolic blood pressure, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, low-density lipoprotein cholesterol, and smoking. In conclusion, high dietary iron intake and an elevated iron/PUFA ratio were associated with the presence of DPN. The present study suggests the importance of the dietary pattern of iron and PUFA intake in individuals with type 2 diabetes.

Aims We evaluated the clinical usefulness of a new unified glucose–insulin–potassium (GIK) regimen in a general surgical department. Methods Surgical patients treated under the previous diverse GIK regimens (September 2016 to August 2017) and the new unified GIK regimen (September 2017 to August 2018) were identified in records of the Clinical Data Warehouse of Seoul National University Bundang Hospital. Serial and area under the curve (AUC) glucose levels, and percentages of time within the target glucose levels were compared in propensity score matched patients in the diverse GIK regimen and in the unified GIK regimen (n = 227 in each group). Results The AUC of glucose at 6 h and 12 h was lower under the unified GIK regimen than the diverse GIK regimen. The percentage of target glucose levels was higher in the unified GIK regimen compared to the diverse GIK regimen (81.5% vs. 75.0%, P = 0.026), but the occurrence of hypoglycaemia did not differ significantly between groups. Conclusions The unified GIK regimen was more effective than the diverse GIK regimen for glycaemic control and did not increase the number of patients developing hypoglycaemia. This validated written GIK regimen can be safely used in a general surgical department.

Objective: The purpose of this study is to evaluate if low muscle mass increases risk of T2D in women with previous gestational diabetes mellitus (pGDM). Methods: A total of 378 women with pGDM (mean age: 35.6 ± 3.9 years) was prospectively evaluated for incidence of T2D. GDM was diagnosed with 75g or 100g oral glucose tolerance test (OGTT) during 24-28 week gestational age. Reclassification of glycemic status was performed with 75g OGTT at 2 months after delivery and lean body mass (LBM) was assessed with bioelectrical impedance analysis (Inbody720, Seoul, Korea). LBM was divided by BMI and this index was divided into 3 tertiles: lowest ≤0.88 (N=107), middle 0.89-0.97 (N=111), highest ≥0.98 group (N=99). The primary outcome was incidence of T2D up to 1 year follow up. Results: The lowest muscle group developed T2D (p=0.007) more than higher muscle groups. The trend for risk developing prediabetes and T2D was significantly increased according to LBM/BMI tertiles (p for trend=0.002). After adjusting family history of T2D, extent of gestational hyperglycemia and waist circumference, lowest group demonstrated HR for developing T2D 6.6 [CI 1.36 to 32.25], p=0.01, compared to the highest group. Conclusion: Lower muscle mass is an independent risk factor for T2D in pGDM. Therefore, it is important to examine muscle mass during risk assessment for T2D in Korean non-obese women with pGDM. Disclosure Y. Shin: None. T. Oh: None. S. Choi: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited.

Introduction: Previous studies demonstrated that older adults with diabetes had lower skeletal muscle mass, strength, and physical function compared with those without diabetes. The aim of this study is to evaluate the effect of hyperglycemia and insulin resistance in the progression of sarcopenia in older adults with diabetes. Methods: The Korean Frailty and Aging Cohort Study is a multicenter prospective study with a baseline examination measured in 2016-2017. Longitudinal analysis was conducted with the 2018 follow up data. The difference of muscle related variables over the two years was evaluated for both genders and stratified by the presence of diabetes and insulin resistance. Results: Among the 1,515 participants with baseline and two-year follow-up examination on skeletal muscle mass, strength, and function, 327 (21.6%) had diabetes mellitus at baseline. Participants showed decline in ASM, ASM/height2, ASM/body mass index (BMI), gait speed, and Timed Up and Go (TUG) test regardless of diabetes status over the two years (all p Conclusion: Insulin resistance shows preponderating influence over hyperglycemia in progression of sarcopenia in Korean older adults. This result suggests that insulin sensitizer might be beneficial in prevention of sarcopenia in older adults with diabetes. Disclosure H. Choe: None. K. Kim: None. T. Oh: None. S. Choi: None. K. Park: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited.

Background: Type 2 diabetes mellitus (T2DM) is interrelated with nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. However, the association between NAFLD and diabetic peripheral neuropathy (DPN) has not been well studied. Methods: We prospectively enrolled subjects with T2DM to evaluate risk factors of DPN and to develop a screening tool of DPN. In this study, we analyzed the data of 127 subjects in whom we could calculate NAFLD and liver fibrosis scores. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Non-invasive markers of NAFLD (hepatic steatosis index, and NAFLD liver fat score) and liver fibrosis (NAFLD fibrosis score, and fibrosis-4 score) were calculated using equations containing several combinations of age, the presence of obesity or metabolic syndrome, liver function test, fasting insulin level, and platelet count. Body composition was measured by bio-impedance analysis. Clinical parameters and various markers were compared according to the presence of DPN. Results: The prevalence of DPN in our study was 39.3%. There was no significant difference in body mass index, diabetes duration, and liver function test between subjects with DPN and those without DPN. Subjects with DPN showed older age, and higher fasting blood glucose level. Hepatic steatosis index and NAFLD liver fat score were comparable between subjects with or without DPN. In contrast, subjects with DPN showed significantly higher NAFLD fibrosis score (-0.7 vs. -1.3, P = 0.004) and fibrosis-4 score (1.6 vs. 1.2, P = 0.014) compared to those without DPN. These two scores were negatively associated with lean body mass. After adjusting lean body mass, the association between liver fibrosis scores and DPN was still significant. Conclusion: The liver fibrosis scores but not NAFLD scores were higher in subjects with DPN compared to those without DPN. Liver fibrosis and DPN might share common pathophysiology. Disclosure K. Kim: None. T. Oh: None. Y. Shin: None. S. Choi: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited.

The impact of baseline HbA1c on the efficacy and safety of fast-acting insulin aspart (FA) was assessed in a post-hoc analysis of a 16-week, treat-to-target trial in adults with type 2 diabetes (T2D) not optimally controlled with a basal-bolus regimen (onset 9). Participants (n=1091) were randomized to FA or insulin aspart (IAsp), each with insulin degludec with or without metformin. In this analysis, participants were separated by baseline HbA1c ( Change from baseline in HbA1c was similar between treatments in the FA provides effective overall glycemic control with improved PPG control vs. IAsp in adults with T2D. For individuals with HbA1c Disclosure E. Franek: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Bioton, Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim, Novo Nordisk. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. Ó. Thórisdóttir: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Rathor: Employee; Self; Novo Nordisk. L. Rose: None. A. Soto Gonzalez: Advisory Panel; Self; Novartis, Novo Nordisk. Consultant; Self; Mundipharma International, Novartis, Novo Nordisk. Speaker’s Bureau; Self; Eli Lilly and Company, Janssen/Mundipharma, Novartis, Novo Nordisk, Sanofi. R.J. Silver: Advisory Panel; Self; Medtronic, Novo Nordisk. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. W. Lane: Research Support; Self; AstraZeneca, Gilead, Mylan, Sanofi, Tolerion, vTv. Other Relationship; Self; Dexcom, Insulet, Novo Nordisk. Funding Novo Nordisk

Background: Screening for diabetic peripheral neuropathy (DPN) is easily omitted in the busy clinical setting. SUDOSCAN is a non-invasive and convenient tool for evaluating small-fiber neuropathy, but its clinical effectiveness for screening of DPN is lacking. We investigated whether SUDOSCAN combined with a neuropathy questionnaire could be an effective tool for screening for DPN in people with type 2 diabetes. Methods: We analysed the data for 197 people with type 2 diabetes without renal dysfunction or changes in their use of anti-hyperglycaemic medications during the past 3 months. The presence of DPN was evaluated using the Michigan Neuropathy Screening Instrument Physical Examination (MNSI-PE). Electrochemical skin conductance (ESC) of the feet was assessed using SUDOSCAN, and the MNSI Questionnaire (MNSI-Q) and 10-gram monofilament tests were conducted. We developed a scoring model including various combinations of clinical parameters and neuropathy examination results. Results: The prevalence of DPN was 42.6%. Participants with DPN were older (59.9 ± 9.5 vs. 56.7 ± 8.8 years) and had a longer duration of diabetes than those without DPN. Feet ESC distinguished the presence of DPN, and the optimal cut-off value was 69.5 uS. The OR for the association between an abnormal feet ESC ( Conclusions: The screening model for DPN that includes SUDOSCAN and the MNSI-Q can detect DPN with acceptable discrimination power and is more convenient than neurophysiological studies. This strategy may be useful in the busy outpatient clinical setting. Disclosure T. Oh: None. K. Kim: None. Y. Shin: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. S. Choi: None. Funding Korean Diabetes Association (2016F-5)

Parous women who did not lactate have increased risk of diabetes compared to nulliparous women, but this risk is normalized by lactating for >3 months. However, the mechanism of the beneficial effects of lactation has not been elucidated. Therefore, we compared metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. For the human study, we recruited gestational diabetes and gestational impaired glucose tolerance women, and performed 75 g oral glucose tolerance test at postpartum 2 months and annually thereafter. Both lactating and non-lactating women showed normal glucose tolerance after 2 months of lactation. However, after a mean 3.6 years from delivery, lactated women maintained similar glucose tolerance whereas glucose tolerance deteriorated over time in non-lactated women. The Disposition index was improved in previously lactated women, suggesting improved β cell function after several years of delivery. For the mouse study, nine-week-old female C57BL/6J mice were mated to give birth and pups were either left (Lactating) or removed (Non-lactating) from the cage at the day of delivery. At 3 weeks after delivery, lactating mice had improved glucose tolerance and increased β cell mass compared to non-lactating mice. Lactating mice maintained high serum prolactin levels, which induced serotonin production in β cell via PRLR-STAT5-TPH1 cascade. Serotonin facilitated β cell proliferation and enhanced β cell function in lactating mice. Amelioration of glucose tolerance and β cell function were maintained for several months after the cessation of lactation in mice. These beneficial effects of lactation, however, were diminished in β cell-specific Tph1 knockout mice. We demonstrated a novel mechanism of 5-HT derivatives acting as a direct anti-oxidant to enhance β cell survival upon oxidative stress. In conclusion, serotonin contributes to the beneficial metabolic effects of lactation by enhancing β cell mass and function. Disclosure J. Moon: None. H. Kim: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. H. Kim: None. Funding National Research Foundation of Korea (2017H1A2A1042095, 2013H1A8A1003985, 2018R1A6A3A01012333, 2015M3A9B3028218, 2018R1A2A3074646)

Aims/Introduction We aimed to examine the prevalence of sarcopenia and frailty in Korean older adults with diabetes compared with individuals without diabetes. Materials and Methods We analyzed the data of 2,403 participants aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study. Sarcopenia was defined using the Asian Working Group for Sarcopenia and the Foundation for the National Institutes of Health. Frailty was assessed by the Cardiovascular Health Study frailty phenotype criteria. Results The mean age of the participants was 76.0 ± 3.9 years, and 47.2% were men. The prevalence of diabetes was 30.2% in men and 25.8% in women. Adults with diabetes showed a lower muscle mass index (appendicular skeletal muscle mass/body mass index) and handgrip strength in both sexes, but only the women showed decreased physical performance. Women with diabetes presented a higher prevalence of sarcopenia diagnosed by the Foundation for the National Institutes of Health criteria, and frailty compared with participants without diabetes (sarcopenia 14.7% vs 8.5%, P = 0.001; frailty 9.5% vs 4.9%, P = 0.003). Men in the high and middle tertiles for homeostatic model assessment of insulin resistance presented a significantly higher prevalence of sarcopenia, compared with men in the low tertile homeostatic model assessment of insulin resistance (high tertile 16.6%, middle tertile 13.3%, low tertile 8.6%). Conclusions In older adults with diabetes, muscle mass index and muscle strength were lower than in those without diabetes. However, the prevalence of sarcopenia and frailty was higher and physical performance was lower only in women with diabetes., We aimed to examine the prevalence of sarcopenia and frailty in Korean older adults with diabetes compared with adults without diabetes using a nationwide cohort study. The muscle mass index and muscle strength in older adults with diabetes were lower than in those without diabetes. However, the prevalence of sarcopenia and frailty was higher, and physical performance was lower only in women with diabetes.

IntroductionCardiovascular disease (CVD) in patients with diabetes is the leading cause of death. Finding early biomarkers for detecting asymptomatic patients with CVD can improve survival. Recently, plasma proteomics—targeted selected reaction monitoring/multiple reaction monitoring analyses (MRM)—has emerged as highly specific and sensitive tools compared with classic ELISA methods. The objective was to identify differentially regulated proteins according to the severity of the coronary artery atherosclerosis.Research design and methodsA discovery cohort, a verification cohort and a validation cohort consisted of 18, 53, and 228 subjects, respectively. The grade of coronary artery stenosis was defined as a percentage of luminal stenosis of the major coronary arteries. Participants were divided into six groups, depending on the presence of diabetes and the grade of coronary artery stenosis. Two mass spectrometric approaches were employed: (1) conventional shotgun liquid chromatography tandem mass spectrometry for a discovery and (2) quantitative MRM for verification and validation. An analysis of the covariance was used to examine the biomarkers’ predictivity beyond conventional cardiovascular risks.ResultsA total of 1349 different proteins were identified from a discovery cohort. We selected 52 proteins based on the tandem mass tag quantitative analysis then summarized as follows: chemokine (C-X-C motif) ligand 7 (CXCL7), apolipoprotein C-II (APOC2), human lipopolysaccharide-binding protein (LBP) and dedicator of cytokinesis 2 (DOCK2) in diabetes; CXCL7, APOC2, LBP, complement 4A (C4A), vitamin D-binding protein (VTDB) and laminin β1 subunit in non-diabetes. Analysis of covariance showed that APOC2, DOCK2, CXCL7 and VTDB were upregulated and C4A was downregulated in patients with diabetes showing severe coronary artery stenosis. LBP and VTDB were downregulated in patients without diabetes, showing severe coronary artery stenosis.ConclusionWe identified significant associations between circulating APOC2, C4A, CXCL7, DOCK2, LBP and VTDB levels and the degree of coronary artery stenosis using the MRM technique.

Context The long-term association between multiple cytokines and progression to diabetes is still uncertain. Objective To identify which cytokines could predict progression to prediabetes and type 2 diabetes over 10 years. Methods The study included 912 participants aged 40 to 69 years at baseline from the Ansung cohort, part of the Korea Genome Epidemiology Study. At baseline, a 75-g oral glucose tolerance test and 8 cytokines were measured: plasminogen activator inhibitor 1 (PAI-1), resistin, interleukin 6, leptin, monocyte chemoattractant protein 1, tumor necrosis factor alpha, retinol binding protein 4 (RBP4), and adiponectin. People with normal glucose tolerance (NGT, n = 241) and prediabetes (n = 330) were followed-up biennially for 10 years. Multinomial logistic regression analysis was used to evaluate the predictability of cytokines on the new-onset prediabetes and type 2 diabetes. Results At 10 years, 38 (15.8%) and 82 (34.0%) of those with NGT had converted to prediabetes and type 2 diabetes, respectively. Of those with prediabetes, 228 (69.1%) had converted to type 2 diabetes. In people with NGT or prediabetes at baseline, the highest tertile of RBP4 was associated with a 5.48-fold and 2.43-fold higher risk of progression to type 2 diabetes, respectively. The odds for converting from NGT to prediabetes in the highest tertile of PAI-1 and the lowest tertile of adiponectin were 3.23 and 3.37, respectively. In people with prediabetes at baseline, those in the highest tertile of resistin were 2.94 time more likely to develop type 2 diabetes (all P < 0.05). Conclusions In this 10-year prospective study, NGT with higher serum RBP4 and PAI-1, and with lower adiponectin were associated with new-onset prediabetes and type 2 diabetes.

OBJECTIVE This study evaluated the efficacy of a smartphone-based, patient-centered diabetes care system (mDiabetes) for type 2 diabetes that contains comprehensive modules for glucose monitoring, diet, physical activity, and a clinical decision support system. RESEARCH DESIGN AND METHODS We conducted a 24-week, multicenter, randomized controlled trial with adult patients with inadequately controlled type 2 diabetes. The patients were randomly assigned to the mDiabetes group or the paper logbook (pLogbook) group. The primary end point was the difference of the change in HbA1c from baseline between the two groups. RESULTS HbA1c reduction from baseline was greater in the mDiabetes group (−0.40 ± 0.09%, n = 90) than in the pLogbook group (−0.06 ± 0.10%, n = 82). The difference of adjusted mean changes was 0.35% (95% CI 0.14–0.55, P = 0.001). The proportion of patients whose HbA1c fell below 7.0% (53 mmol/mol) was 41.1% for the mDiabetes group and 20.7% for the pLogbook group (odds ratio [OR] 2.01, 95% CI 1.24–3.25, P = 0.003). The percentage of patients who attained HbA1c levels below 7.0% (53 mmol/mol) without hypoglycemia was 31.1% in the mDiabetes group and 17.1% in the pLogbook group (OR 1.82, 95% CI 1.03–3.21, P = 0.024). There was no difference in the event numbers of severe hyperglycemia and hypoglycemia between the two groups. CONCLUSIONS The implementation of the mDiabetes for patients with inadequately controlled type 2 diabetes resulted in a significant reduction in HbA1c levels, with tolerable safety profiles.

We investigated the effect of a combination treatment with dapagliflozin (Dapa), a sodium-glucose cotransporter-2 inhibitor and butyrate on weight change in db/db mice. Six-week-old male db/db mice were assigned to four groups: vehicle with normal chow diet (NCD), Dapa with NCD, vehicle with 5% sodium butyrate-supplemented NCD (NaB), or Dapa with 5% NaB. After six weeks of treatment, faecal microbiota composition was analysed by sequencing 16S ribosomal RNA genes. In the vehicle with NaB and Dapa + NaB groups, body weight increase was attenuated, and amount of food intake decreased compared with the vehicle with the NCD group. The Dapa + NaB group gained the least total and abdominal fat from baseline. Intestinal microbiota of this group was characterized by a decrease of the Firmicutes to Bacteroidetes ratio, a decrease of Adlercreutzia and Alistipes, as well as an increase of Streptococcus. In addition, the proportion of Adlercreutzia and Alistipes showed a positive correlation with total fat gain, whereas Streptococcus showed a negative correlation. Inferred metagenome function revealed that tryptophan metabolism was upregulated by NaB treatment. We demonstrated a synergistic effect of Dapa and NaB treatment on adiposity reduction, and this phenomenon might be related to intestinal microbiota alteration.

Background Diabetic peripheral neuropathy (DPN) is prevalent in patients with type 2 diabetes, and its prevalence increases with age. A previous study demonstrated the association between DPN and muscle dysfunction; however, there are limited data on the association between DPN and sarcopenia. Methods We enrolled patients with type 2 diabetes and measured hand grip strength (HGS), lean body mass using a bio-impedance analysis, and gait speed using a 4-m walking test. Sarcopenia was diagnosed according to the criteria from the Asian Working Group for Sarcopenia. We also performed various examinations of neuropathy, including both small- and large-fiber neuropathy. Results Among 170 participants (mean age, 61.5±6.6 years), 24 (14.1%) were diagnosed with sarcopenia. The Michigan Neuropathy Screening Instrument Questionnaire (MNSI-Q) scores were higher in patients with sarcopenia than in those without sarcopenia (2.7±1.3 vs. 2.4±1.3; p=0.008). However, other neuropathy examination results were not significantly associated with sarcopenia. The MNSI-Q score was negatively associated with HGS, with an odds ratio (OR) of 1.367 (95% confidence interval [CI], 1.122-1.667) in predicting the presence of sarcopenia. After adjusting for sex, body mass index, and diabetes duration, the MNSI-Q score was associated with the presence of sarcopenia (adjusted OR=1.310; 95% CI, 1.041-1.647). Conclusion In this population with type 2 diabetes, patients with sarcopenia had higher neuropathy questionnaire scores than those without sarcopenia. Therefore, active screening for sarcopenia should be performed in subjects with DPN.

BackgroundFibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has beneficial effects on glucose and lipid metabolism. However, plasma FGF21 levels are paradoxically increased in type 2 diabetes mellitus (T2DM) and obesity, suggesting resistance to this ligand. FGF21 acts mainly on adipose tissue and ectopic fat accumulation is a typical feature in metabolic deterioration such as diabetes, metabolic syndrome, and cardiovascular disease.ObjectiveTo investigate the relationship between FGF21 resistance and ectopic fat accumulation.Research design and methodsSubjects who underwent 64-slice multidetector CT (MDCT) were enrolled (n=190). Plasma FGF21 levels and MDCT data of ectopic fats at various sites were analyzed. Human visceral and subcutaneous fat tissues from abdominal and coronary artery bypass surgery were obtained. FGF21 receptor expression and postreceptor signaling in different fat deposits of both control and T2DM subjects were analyzed.ResultsPlasma FGF21 levels were significantly associated with body mass index, triglyceride, homeostatic model assessment of insulin resistance, and Matsuda index. Plasma FGF21 levels were significantly higher in patients with T2DM than in the pre-diabetes and normal glucose tolerance groups. The ectopic fat phenotypes (visceral, epicardial, intrahepatic, and intramuscular fat) of T2DM were significantly higher than controls. Plasma FGF21 levels were elevated and exhibited a strong positive correlation with ectopic fat accumulation in T2DM. The expression of genes comprising the FGF21 signaling pathway was also lower in visceral fat than in subcutaneous fat in this disease.ConclusionsHuman FGF21 resistance in T2DM could result from increases in FGF21-resistant ectopic fat accumulation. Our study provides novel clinical evidence linking FGF21 resistance and T2DM pathogenesis.

AIM To compare pancreatic volume and fat amount, and their associations with glucose homeostasis, in a Korean and a white population. MATERIALS AND METHODS In 43 healthy Korean and 43 healthy white people, matched for age (±3 years) and body mass index (BMI; ±1 kg/m2 ), we measured pancreatic volume and fat amount in the pancreas and abdomen using computed tomography. Pancreatic β-cell function and insulin resistance were estimated according to biochemical characteristics and a 75-g oral glucose tolerance test. Body composition and resting energy expenditure (REE) were examined using bioimpedance and indirect calorimetry, respectively. RESULTS The mean ±SD age of the participants was 29.9 ± 5.9 years and 30.0 ± 5.2 years, and BMI was 24.0 ±3.7 and 24.1 ±3.2 kg/m2 in the white participants and the Korean participants, respectively. Pancreatic volume in the white participants was greater than that in Korean participants (77.8 ±11.6 vs 68.2 ±12.1 cm3 ; P

Adipogenesis is the process of differentiation from preadipocytes to adipocytes and is orchestrated by various transcription factors, such as the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). Oxidative stress is also a crucial factor in adipogenesis, and adipocyte differentiation is affected by the cellular redox status. The nuclear factor E2-related factor 2 (Nrf2), which is a basic leucine zipper (bZIP) transcription factor, acts as a regulator of cellular oxidative stress. Although several previous studies examined the function of Nrf2 in adipogenesis, their results were controversial. In this study, we investigated whether the suppression of Nrf2 in 3T3-L1 cells affected adipogenesis. We found that adipogenesis master regulator genes, such as PPARγ and C/EBPα, were downregulated during the differentiation stage in Nrf2-knockdown 3T3-L1 cells. Moreover, the fibroblast growth factor 21 (FGF21) and manganese superoxide dismutase (MnSOD) were markedly downregulated in Nrf2-knockdown 3T3-L1 cells. Taken together, the results of the present study suggest that the suppression of Nrf2 attenuates adipogenesis and decreases FGF21 expression through PPARγ in 3T3-L1 cells.

Background Quality and quantity of high-density lipoprotein cholesterol (HDL-C) may be associated with cardiovascular risk. We investigated the effect of rosuvastatin on cholesterol efflux (CE) for HDL function and vascular health.Methods and Results:We enrolled 30 dyslipidemic patients with type 2 diabetes mellitus and 20 healthy subjects as controls. Vascular health was assessed on flow-medicated dilation (FMD), nitroglycerin-induced dilatation of the brachial artery and carotid artery intima-media thickness (cIMT). These parameters were compared between patients and controls, and between baseline and at 12 weeks of treatment with rosuvastatin 20 mg. Age and body mass index were 49.8±11.3 years and 25.8±3.7 kg/m2in the patients, and 28.8±3.2 years and 22.4±2.4 kg/m2in the controls, respectively. The biomarkers related to lipid and glucose metabolism and lipoprotein (a), high-sensitivity C-reactive protein, and cIMT were significantly higher, and CE and FMD were significantly lower in the patients than in the controls. In the patients, rosuvastatin 20 mg decreased low-density lipoprotein cholesterol by 54.1% and increased HDL-C by 4.8%. The CE increased significantly after rosuvastatin treatment (12.26±2.72% vs. 14.05±4.14%). FMD also increased, and lipoprotein (a) and cIMT decreased significantly and were associated with changes of CE. Conclusions Rosuvastatin-induced changes in HDL function are significantly associated with cardiovascular benefit.

There are inconsistent results for the effectiveness of using smartphone applications (apps) or websites on weight loss. We investigated the efficacy of a smartphone intervention using a designated app that utilizes a lifestyle intervention-focused approach, including a human coaching element, toward weight loss in overweight or obese Korean adults.One hundred four adults aged 20-60 years with a body mass index ≥23 kg/mParticipants showed a clinically significant weight loss effect of -7.5% at the end of the 15-week program (P 0.001), and at a 52-week follow-up, a weight loss effect of -5.2% was maintained. At 15 weeks, percent body fat and visceral fat decreased by -6.0 ± 5.4% and -3.4 ± 2.7 kg, respectively (both P 0.001). Fasting glucose level also decreased significantly by -5.7 ± 14.6 mg/dL at 15 weeks. Lipid parameters showed significant improvements, except for high-density lipoprotein cholesterol. The frequency of logging meals and exercise was associated with body fat loss.This advanced smartphone app was a useful tool to maintain weight loss in overweight or obese people.

Objectives The relationship between the renin–angiotensin system (RAS) and diabetes has been studied for many years. However, studies that assessed RAS components comprehensively were limited. We hypothesized that serum RAS components, especially the effector peptide angiotensin-II, might be closely associated with glucose metabolism status and diabetic complications. Methods We investigated the association of individual RAS component with albuminuria in 407 subjects with normal glucose metabolism (NGM), prediabetes, or type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters, including glucose homeostasis, albuminuria, and RAS-related parameters such as plasma renin activity (PRA), aldosterone, angiotensin-converting enzyme (ACE), and angiotensin-II levels, were measured. Results The mean±standard deviation (SD) age and body mass index were 57.1±11.1years and 24.7±3.3kg/m 2 , respectively. There were 54 subjects with NGM, 102 with prediabetes, and 251 with T2DM. The mean±SD angiotensin-II levels in these groups were 9.32±6.89, 12.89±10.39, and 17.00±15.28pg/mL, and the respective urinary albumin-to-creatinine ratios (ACRs) were 8.1±5.3, 13.3±17.3, and 30.7±51.9mg/g, which were significantly different among the groups. The serum angiotensin-II levels were correlated with levels of PRA, insulin resistance, C-reactive protein, and urinary ACR. Among RAS-related parameters, only the angiotensin-II level was significantly associated with urinary ACR after adjusting for relevant risk factors. Conclusions Angiotensin-II may play an important role in the development of albuminuria, particularly in subjects with impaired glucose metabolism.

Chronic kidney disease (CKD) has often been defined based on glomerular filtration rate (GFR) alone. The Kidney Disease: Improving Global Outcomes guideline highlights albuminuria in the CKD definition. Thus, we investigated the association between obesity and CKD, as defined by both GFR and albuminuria, in Korean adults.We used Korea National Health and Nutrition Examination Survey 2011-2014 data (N = 19,331, ≥19 years old) representing the national Korean population. CKD was classified by (1) estimated GFR (eGFR) 60 mL/min/1.73 mThe prevalence rates of CKDObesity was significantly associated with an increased ACR-based CKD risk. Longitudinal studies are needed to investigate the role of overweight and obesity in the development and progression of CKD.

Background Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone. Methods MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 μM), rosiglitazone (0.4 μM), or pioglitazone (1 μM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment. Results As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice. Conclusion These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.

BACKGROUND The aim of this study was to investigate the glucose-lowering efficacy of antidiabetic treatments in patients with type 2 diabetes mellitus (T2DM) uncontrolled by sulfonylurea plus metformin. METHODS This open-label, multicenter, prospective, observational study was conducted in 144 centers in Korea, from June 2008 to July 2010, and included patients with T2DM who had received sulfonylurea and metformin for at least 3 months and had levels of glycosylated hemoglobin (HbA1c) >7.0% in the last month. Data of clinical and biochemical characteristics were collected at baseline and 6 months after treatment. The treatment option was decided at the physician's discretion. Subjects were classified into the following three groups: intensifying oral hypoglycemic agents (group A), adding basal insulin (group B), or starting intensified insulin therapy (group C). RESULTS Of 2,995 patients enrolled, 2,901 patients were evaluated, and 504 (17.4%), 2,316 (79.8%), and 81 patients (2.8%) were classified into groups A, B, and C, respectively. Subjects in group C showed relatively higher baseline levels of HbA1c and longer duration of diabetes. The mean decrease in HbA1c level was higher in the insulin treated groups (-0.9%±1.3%, -1.6%±1.3%, and -2.4%±2.3% in groups A, B, and C, respectively, P=0.042). The proportion of patients who achieved target HbA1c

Background and aims Sarpogrelate, a 5-hydroxytryptamine type 2A antagonist, is a potential antiplatelet agent. We performed a randomized study to evaluate the effect of sarpogrelate on vascular health in Korean patients with diabetes. Methods Forty diabetic patients aged 58.6 ± 6.8 years with 10–75% coronary artery stenosis, as assessed by coronary computed tomography angiography, were randomly assigned to sarpogrelate 300 mg/day plus aspirin 100 mg/day (SPG + ASA group) or aspirin 100 mg/day alone (ASA group) for 6 months. The primary endpoint of this study was the change in coronary artery disease including the calcium score (CACS), maximal stenosis, and plaque volume (calcified vs. noncalcified). The secondary endpoints were changes in biochemical parameters related to glucose and lipid metabolism, and in subclinical atherosclerosis assessed by ankle–brachial index and pulse wave velocity. Results After 6-month treatment, there was no significant difference in the changes in CACS, coronary stenosis, ankle–brachial index, and pulse wave velocity, between groups. The total plaque volume decreased from 82.4 ± 14.5 mm 3 to 74.6 ± 14.4 mm 3 in the SPG + ASA group, but increased from 64.9 ± 16.0 mm 3 to 68.6 ± 16.3 mm 3 in the ASA group ( p 3 to 11.2 ± 3.7 mm 3 vs . ASA group 21.2 ± 6.2 mm 3 to 22.8 ± 6.6 mm 3 , p Conclusions The present study demonstrated that sarpogrelate treatment may decrease coronary artery plaque volume, particularly the noncalcified portion, in patients with diabetes.

Objectives: The aim of this study was to investigate associations between skeletal muscle mass and bone mineral density according to gender and skeletal sites. Methods: Using the data from Korean National Health and Nutrition Examination Survey (KNHANES IV) 2009, a total of 711 males and 847 females over 65 years of age were evaluated. Bone mineral density (BMD) and body composition were assessed using dual-energy X-ray absorptiometry. Results: Relative appendicular skeletal muscle (RASM) was positively related with the femur BMD with a stronger relationship in males (r = 0.207, p

SummaryObjective In Caucasians, plasma glucose concentration at 1 h during an oral glucose tolerance test (OGTT) may be a better predictor of future diabetes mellitus than the fasting or 2-h postload glucose concentration. We investigated whether the 1-h glucose concentration could be used to predict future diabetes mellitus in Asian ethnicity. Measurements A total of 5703 Koreans with normal glucose tolerance were enrolled from the Korean Genome and Epidemiology Study. Indices of insulin sensitivity and β-cell function estimated from standard 75-g OGTTs performed every 2 years for 12 years were used to identify whether the 1-h glucose concentration could predict future diabetes mellitus. Results The mean age and body mass index at baseline were 51·3 ± 8·7 years and 24·2 ± 3·0 kg/m2, respectively. During the 12-year follow-up, 593 subjects (10·3%) developed diabetes mellitus. The area under the receiver-operating characteristic curve for incident diabetes mellitus was higher for the 1-h postload glucose concentration than for the fasting or postload 2-h glucose concentration (0·74 vs 0·61 or 0·63). The cut-off value of ≥8·0 mmol/l identified incident diabetes mellitus with 70% sensitivity and 68% specificity. After adjusting for typical risk factors, subjects with a 1-h postload glucose concentration ≥8·0 mmol/l had lower β-cell function and a 2·84-fold increased risk of incident diabetes mellitus compared with their counterparts. Conclusions In this community-based 12-year prospective cohort study, 1-h postload plasma glucose concentration was an independent predictor of future diabetes mellitus and 8·0 mmol/l was suggested as a cut-off value.