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The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (–0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was –0.9%±1.2% (P

Background: To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term dura ble glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (

Aims/Introduction We investigated the risk of incident type 2 diabetes according to the cumulative exposure to obesity or metabolic syndrome (MetS) during annual or biennial health examinations. Materials and Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this retrospective longitudinal study. The risk for type 2 diabetes was analyzed according to the cumulative exposure to obesity and MetS among individuals who underwent four health examinations from 2009 to 2012 or 2013 (n = 2,851,745). Results During examinations, 28.56 and 17.86% of the total participants showed fluctuations in metabolic health state and obesity, respectively. During a mean 5.01 years of follow up, 98,950 new type 2 diabetes cases developed. The risk for type 2 diabetes increased with the increase in exposure to MetS (hazard ratio [HR] 2.92, 95% confidence interval [CI] 2.86–2.99; HR 4.96, 95% CI 4.85–5.08; HR 7.46, 95% CI 7.30–7.63; HR 12.24, 95% CI 12.00–12.49 in groups with number of exposures one to four, respectively) and obesity (HR 1.60, 95% CI 1.56–1.65; HR 1.87, 95% CI 1.81–1.92; HR 2.25, 95% CI 2.19–2.31; HR 3.46, 95% CI 3.41–3.51 in groups with number of exposures one to four, respectively), showing a more detrimental effect of cumulative exposure to MetS, when compared with the exposure to obesity. Conclusions Metabolic health and obesity fluctuated within a relatively short period of 4–5 years. Although the impact was much greater for MetS than for obesity, the cumulative duration of both obesity and MetS was associated with an increased risk of type 2 diabetes in a dose‐response manner. Therefore, continuously maintaining metabolic health and normal weight is crucial to prevent incident type 2 diabetes., In this large‐scale longitudinal study including 2,851,745 Korean adults with four annual or biennial health examinations, the metabolic health and obesity status fluctuated within a relatively short period of 4–5 years. The cumulative exposure to both metabolic syndrome and obesity was associated with an increased hazard of incident type 2 diabetes in a graded dose‐response manner, although the exposure to metabolic syndrome had a much greater impact than the exposure to obesity. Continuously maintaining metabolic health and normal weight would be warranted to prevent incident type 2 diabetes.

Background Diabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes. Methods We included 152,931 individuals without diabetes from the Korean National Health Insurance Service–Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM). Results A total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan–Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P P Conclusions Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes. Graphical Abstract

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P

OBJECTIVE: This study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to coronavirus disease 2019 (COVID-19) outcomes. METHODS: We analyzed 4,069 COVID-19 patients between January and June 2020 in South Korea, classified into four groups according to metabolic health status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). The primary outcome was a composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), extracorporeal membrane oxygenation (ECMO), and death. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for the outcome. RESULTS: The incidence rate (per 100 person-months) of severe COVID-19 outcomes was the lowest in the MHNW group (0.90), followed by the MHO (1.64), MUNW (3.37), and MUO (3.37) groups. Compared with MHNW, a significantly increased risk of severe COVID-19 was observed in MUNW (HR, 1.41;95% CI, 1.01-1.98) and MUO (HR, 1.77;95% CI, 1.39-2.44) but not in MHO (HR, 1.48;95% CI, 0.98-2.23). The risk of ICU admission or IMV/ECMO was increased only in MUO;however, the risk of death was significantly higher in MUNW and MUO. The risk of severe COVID-19 increased insignificantly by 2% per 1 kg/m2 BMI increase but significantly by 13% per 1 metabolically unhealthy component increase, even after mutually adjusting for BMI and metabolic health status. CONCLUSION: Metabolic health is more important to COVID-19 outcomes than obesity.

Physical exercise plays an important role in both the prevention and treatment of cardiometabolic diseases. Peptides secreted or released from skeletal muscle, so-called myokines, contribute to the beneficial anti-inflammatory and insulin-sensitizing effects of increased muscle activity and may, therefore, counteract pathomechanisms of obesity and type 2 diabetes (T2D) [1]. However, the impact of myokines including interleukin (IL)-6, IL-8, IL-13, IL-15, angiopoietin-like 4 (ANGPTL4), fibroblast growth factors (FGF)-2, FGF-21, and irisin on altered organ cross-talk in cardiometabolic diseases is still poorly understood [1]. Irisin has been described as a protein released from skeletal muscle after physical activity [2] which may, in rodents and more controversially discussed in humans [1], mediate browning of white adipose tissue. Although the existence of circulating human irisin has even been questioned because human FNDC5 has a noncanonical ATA translation start, irisin has been detected in human plasma using mass spectrometry with appropriate control peptides [3]. IL-15 increases upon both aerobic and resistance exercise and exerts beneficial metabolic effects in patients with obesity and T2D [1]. IL-15 inhibits lipogenesis, induces fat oxidation, enhances energy expenditure, and improves insulin sensitivity and glucose metabolism [4]. To better understand the potential role of these myokines in T2D, we tested the hypotheses that IL-15 and irisin serum concentrations correlate with cardiometabolic risk parameters and are different in subgroups of T2D patients with or without diabetes complications independently of ethnicity.

Background: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naive newly-diagnosed type 2 diabetes mellitus. Methods: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was mea sured at week 24. Results: The reduction in the levels of HbA1c was -1.62%±0.07% in the vogmet group and -1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of

BackgroundThe global incidence of NAFLD is rising sharply due to various risk factors. As previous studies reported adverse health impact of long working hours on metabolic diseases, such as diabetes mellitus and obesity, it is plausible that NAFLD is also associated with working excessive hours. However, data regarding this issue is limited.MethodsIn this cross-sectional study based on Korea National Health and Nutrition Examination Survey VII, 5,661 working adults without previous liver disease or heavy alcohol drinking habits were included. The subjects were categorized into three groups according to working hours: 36–42, 43–52, and 53–83 hours/week. NAFLD was defined using the hepatic steatosis index (HSI), which is a validated prediction model for determining NAFLD.ResultsThe prevalence of NAFLD (HSI ≥36) increased with longer working hours: 23.0%, 25.6%, and 30.6% in the 36–42, 43–52, and 53–83 hours/week group, respectively (p vs. shift workers) or occupation type (office vs. manual workers). In particular, the relationship between long working hours and NAFLD was pronounced in workers aged ConclusionsLong working hours was significantly associated with NAFLD. Further prospective studies are required to validate this finding with causal relationship.

Aim Although few recent studies have reported the association between the glycemic variability and the development of type 2 diabetes mellitus and cardiovascular disease in individuals without diabetes mellitus, the impact of the long-term variability in fasting plasma glucose (FPG) levels on the incident nonalcoholic fatty liver disease (NAFLD) has not been evaluated. Methods The study included 57,636 Korean men and women without NAFLD and diabetes mellitus from the Korean National Health Insurance System cohort. FPG variability was calculated using the coefficient of variation (FPG-CV), standard deviation (FPG-SD), variability independent of the mean (FPG-VIM), and average successive variability (FPG-ASV). Results The cumulative incidence of NAFLD demonstrated progressively increasing trends according to the higher quartiles of FPG variability in Kaplan-Meier curves. A multivariable Cox proportional hazard analysis revealed that the hazard ratio for incident NAFLD was 1.15 (95% confidence interval, 1.06–1.24) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for various confounding factors, including mean FPG levels. When using FPG-SD, FPG-VIM, and FPG-ASV, the results were similar. The 10-unit increase in FPG variability was associated with a 14% increased risk of NAFLD in the fully adjusted model. Moreover, this effect remained consistent in the subgroup and sensitivity analyses. Conclusion Increased long-term FPG variability is associated with the development of NAFLD, independent of confounding risk variables including mean FPG levels.

Context Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. Objective We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. Methods Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). Results Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. Conclusion FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.

Background Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations. We investigated whether variability in long-term fasting plasma glucose (FG) can predict the development of stroke, myocardial infarction (MI), and all-cause mortality in patients with diabetes. Methods This is a retrospective cohort study using the data provided by the Korean National Health Insurance Corporation. A total of 624,237 Koreans ≥ 20 years old with diabetes who had undergone health examinations at least twice from 2005 to 2008 and simultaneously more than once from 2009 to 2010 (baseline) without previous histories of stroke or MI. As a parameter of variability of FG, variability independent of mean (VIM) was calculated using FG levels measured at least three times during the 5 years until the baseline. Study endpoints were incident stroke, MI, and all-cause mortality through December 31, 2017. Results During follow-up, 25,038 cases of stroke, 15,832 cases of MI, and 44,716 deaths were identified. As the quartile of FG VIM increased, the risk of clinical outcomes serially increased after adjustment for confounding factors including duration and medications of diabetes and the mean FG. Adjusted hazard ratios (95% confidence intervals) of FG VIM quartile 4 compared with quartile 1 were 1.20 (1.16–1.24), 1.20 (1.15–1.25), and 1.32 (1.29–1.36) for stroke, MI and all-cause mortality, respectively. The impact of FG variability was higher in the elderly and those with a longer duration of diabetes and lower FG levels. Conclusions In diabetes, long-term glucose variability showed a dose–response relationship with the risk of stroke, MI, and all-cause mortality in this nationwide observational study.

We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.

Persistent organic pollutants(POPs) are suggested to be potential risk factors for gestational diabetes mellitus(GDM). We examined the hypothesis that the aryl hydrocarbon receptor trans-activating(AhRT) activity, a potential biomarker for the presence of POPs, could be a GDM risk factor in pregnant women. A total of 390 GDM and 100 normal pregnant(non-GDM) subjects in the Korea National Diabetes Program cohort voluntarily participated. We measured AhRT activity and concentrations of ATP and reactive oxygen in the serum collected at the screening of the participants for GDM using recombinant Hepa1c1c7 cells. Odds ratios(ORs) and 95% confidence intervals(CIs) were estimated using multivariable logistic regression models. The sensitivity and specificity of AhRT activity for GDM diagnostics were measured by receiver operating characteristic(ROC) analysis. Body mass index at pre-pregnancy and delivery and systolic blood pressure were significantly higher in the GDM group. AhRT activity was higher, and ATP concentrations were lower in the GDM group than the non-GDM group(P P 2 = 0.387) and negatively correlated with ATP production(r2 = −0.650). In the ROC curve, AhRT activity had 70.9% sensitivity and 90.0% specificity for glucose-50, a GDM screening method. In conclusion, this study suggests that serum AhRT activity is positively associated with the risk of GDM.

Aims Pre-pregnancy insulin resistance is one of the main pathophysiologies of gestational diabetes mellitus (GDM). Triglyceride-glucose (TyG) index is a marker of insulin resistance. We aimed to evaluate the association between pre-pregnancy TyG index and GDM in primipara women. Methods A total of 380,208 women who underwent a Korean national health screening exam within 2 years before their first delivery, between January 1, 2012 and December 31, 2015, were included. The TyG index was calculated as ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Among the 380,208 primipara women, 17,239 women were diagnosed with GDM (4.53%). Multivariate logistic regression analysis adjusted for risk factors showed a higher odds ratio of 1.73 for GDM (95% CI 1.65-1.81) in the highest quartile than that in the lowest quartile. A 1-SD increase in the TyG index increased the risk of GDM (31%) and GDM requiring insulin therapy (82%) in the fully adjusted model. A 1-unit increase in the TyG index significantly increased the risk of GDM and GDM requiring insulin treatment by 1.81 and 3.69 times, respectively.The impact of a high TyG index on the risk of GDM was more profound in the subjects aged ≥ 35 years, with obesity, with impaired fasting glucose, who are current smokers, and with a family history of diabetes mellitus. Conclusions Increased pre-pregnancy TyG index is associated with a risk of GDM. Elevation of the TyG index may be an early marker of GDM.

Background We aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status. Methods The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009–2010 and 2013–2014 (N = 7,148,763). Results During two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579–2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039–1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508–0.849)]. Conclusion Dynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3–5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF.

ObjectiveVariability in estimated glomerular filtration rate (eGFR) has been associated with adverse outcomes in patients with diabetes or chronic kidney disease (CKD). However, no previous study has explored the relationship between eGFR variability and type 2 diabetes incidence.Research design and methodsIn this nationwide, longitudinal, cohort study, we investigated the association between eGFR variability and type 2 diabetes risk using the Korean National Health Insurance Service datasets from 2002 to 2017. eGFR variability was calculated using the variability independent of the mean (eGFR-VIM), coefficient of variation (eGFR-CV), standard deviation (eGFR-SD) and average real variability (eGFR-ARV).ResultsWithin 7 673 905.58 person-years of follow-up (mean follow-up: 3.19 years; n=2 402 668), 11 981 cases of incident type 2 diabetes were reported. The HRs and 95% CIs for incident type 2 diabetes increased according to advance in quartiles of eGFR-VIM (HR (95% CI): Q2, 1.068 (1.009 to 1.130); Q3, 1.077 (1.018 to 1.138); Q4, 1.203 (1.139 to 1.270)) even after adjusting for confounding factors including mean eGFR and mean fasting plasma glucose levels. The subgroup analyses according to risk factors as well as analyses using eGFR-CV, eGFR-SD and eGFR-ARV showed consistent results. The association between increased eGFR variability and type 2 diabetes risk was more prominent in men, individuals with dyslipidemia and those with CKD as shown in the subgroup analysis (p for interaction ConclusionsIncreased eGFR variability may be an independent predictor of type 2 diabetes and might be useful for risk stratification of individuals without diabetes.

Aims Previous in-vitro and in-vivo experimental studies have shown that Sestrin2 attenuates oxidative stress and the pro-inflammatory pathway, resulting in improving metabolic homeostasis. However, the relationship between circulating Sestrin2 concentration and cardiometabolic risks in humans has not been explored. Methods Sestrin2 concentration was measured in 240 subjects (46 without diabetes and 194 with diabetes), and the associations between Sestrin2 level and various cardiometabolic risk factors including body composition, insulin resistance, and atherosclerosis was assessed. Results Sestrin2 concentration showed a trend of increasing in subjects with metabolic syndrome. After adjustment for age and gender, Sestrin2 level had a positive relationship with serum triglyceride, alanine aminotransferase (ALT), and creatinine levels, but no association with carotid atherosclerosis. Especially, in subjects with type 2 diabetes Sestrin2 concentration exhibited a significant positive correlation with body mass index (P = 0.015), waist circumference (P = 0.020), high-sensitivity C-reactive protein (P = 0.008), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (P = 0.041), percentage body fat (P = 0.001), and truncal fat mass (P = 0.005) after adjusting age and gender. Multiple stepwise regression analysis identified age, serum ALT and creatinine levels, and percentage body fat as independent determining factors for Sestrin2 concentration in patients with type 2 diabetes (R2 = 0.173). Conclusions This study is the first to demonstrate a trend for increased Sestrin2 level in subjects with metabolic syndrome. In particular, in subjects with type 2 diabetes, Sestrin2 was significantly related to insulin resistance and percentage body fat, suggesting its potential as a novel modulatory factor for metabolic disorders in humans.

OBJECTIVE Although increasing evidence suggests the association between short-term variability of fasting plasma glucose (FPG) and diabetic complications or mortality, the impact of visit-to-visit variability of FPG on the development of type 2 diabetes (T2D) has not been evaluated. RESEARCH DESIGN AND METHODS Our analysis included 131,744 Korean men and women without diabetes using the Korean National Health Insurance System cohort with periodic health examination program. FPG variability was calculated using the coefficient of variation (FPG-CV), SD (FPG-SD), and variability independent of the mean (FPG-VIM). RESULTS During the median follow-up time of 8.3 years, Kaplan-Meier curves demonstrated lower disease-free probability in the higher FPG variability group compared with the lower FPG variability group. Multivariable Cox proportional hazards analysis exhibited that the hazard ratio for incident T2D was 1.67 (95% CI 1.58–1.77, P < 0.001) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for confounding variables, including mean FPG. The association between FPG variability and the risk of T2D was consistent when modeling using FPG-SD and FPG-VIM in both normal and impaired fasting glucose groups. A 1 SD increase in the FPG-CV was associated with a 24% increased risk of T2D in the fully adjusted model. CONCLUSIONS Increased variability of FPG is associated with the development of T2D independently of diverse risk factors.

BACKGROUND Sarcopenic obesity (SO) is a serious public health concern, few studies have examined the clinical implications of SO in newly-diagnosed type 2 diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly diagnosed, drug-naive T2DM patients with low muscle mass with abdominal obesity and its association with insulin resistance and other diabetic complications. METHODS We classified 233 drug-naive T2DM subjects into four groups according to abdominal obesity (waist circumference ≥90 cm in men and ≥85 cm in women) and low muscle mass status (appendicular skeletal muscle

BACKGROUND The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition. METHODS A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income. RESULTS Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; P(trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; P(trend)=0.048). In women, lower income was associated with a higher stress level. CONCLUSION Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population.

Aims/Introduction We investigated the failure of monotherapy in patients with type 2 diabetes mellitus in real practice settings. Materials and Methods The Korean National Diabetes Program was a prospective, multicenter observational cohort study of type 2 diabetes mellitus patients in Korea. Of the 3,950 patients enrolled in the study, we studied 998 who were continuously maintained on monotherapy for at least 90 days at six participating centers. To balance the baseline characteristics of patients in each group, we used propensity matching at a 1:1 ratio (metformin vs sulfonylureas) and 4:1 ratio (metformin vs meglitinides and metformin vs alpha‐glucosidase inhibitors [aGIs]). The hazard ratios (HRs) of treatments (compared with metformin) were determined by Cox's proportional hazards regression modeling. Results The median follow‐up time was 56 months, and monotherapy failed in 45% of all patients. The annual incidences of failure were 15.6%, 21.3%, 27% and 9.6% in the metformin, sulfonylurea, meglitinide and aGI groups. Compared with metformin, sulfonylureas and meglitinides were associated with higher risks of monotherapy failure (HR 1.39, 95% confidence interval [CI] 1.08–1.80; HR 1.92, 95% CI 1.13–3.27), and aGIs with risks similar to that of metformin (HR 0.80, 95% CI 0.44–1.45). When analyzed by failure type, sulfonylureas, meglitinides and aGIs were associated with a higher risk of a switch to other agents (HR 4.43, 95% CI 2.14–9.17; HR 18.80, 95% CI 6.21–56.93; HR 4.25, 95% CI 1.49–12.13), and aGIs with a lower risk of prescription of add‐on second agents (HR 0.16, 95% CI 0.04–0.64). Conclusions Metformin was associated with a lower failure risk than were sulfonylureas and meglitinides, but a comparable aGI failure rate.

Background Previous studies have shown that chronic kidney disease (CKD) is associated with accelerated loss of skeletal muscle in patients on dialysis. However, the relationships of sarcopenia with albuminuria and early-stage CKD in patients with type 2 diabetes have not been examined. Methods We analyzed diabetic subgroup data from 409 patients with type 2 diabetes from the Korean Sarcopenic Obesity Study (KSOS). Sarcopenia was defined as a skeletal muscle mass index (SMI; SMI [%] = total skeletal muscle mass [kg]/weight [kg] × 100) less than 2 SD below the sex-specific mean for a younger reference group. The estimated glomerular filtration rates and urinary albumin-to-creatinine ratios were used to assess renal function and albuminuria. Results The prevalence of sarcopenia was significantly increased in the albuminuria group compared with the normo-albuminuria group (26.7% vs 12.6%, p = .001), as well as in CKD 3 group compared with the CKD 1–2 group (46.7% vs 15.1%, p = .005). After adjusting for age, SMI was negatively correlated with urinary albumin-to-creatinine ratios and positively correlated with aspartate aminotransferase, alanine aminotransferase, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. Multiple logistic regression analysis revealed that the odds ratio for albuminuria association was 3.02 (95% CI 1.37–6.67) in the lowest tertile of SMI compared with the highest tertile after adjusting for various confounding factors. Conclusions Sarcopenia is more prevalent in individuals with albuminuria than in those without albuminuria. Furthermore, increased albuminuria is independently associated with low muscle mass in patients with type 2 diabetes.

Background The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain. Methods The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex. Results In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups. Conclusion Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

Objectives: A recent experimental study revealed that family with sequence similarity 19 [chemokine (C-C motif)-like] member A5 (FAM19A5), a novel secreted adipokine, has inhibitory effects on vascular smooth muscle cell proliferation and migration, and on neointima formation in injured arteries. We investigated the associations between serum FAM19A5 concentration and cardio-metabolic risk factors for the first time in human subjects. Methods: Circulating FAM19A5 concentrations and their associations with cardio-metabolic risk factors were explored in 223 individuals (45 without diabetes and 178 with type 2 diabetes). Results: Serum FAM19A5 concentrations (pg/mL) were greater in patients with type 2 diabetes [median (interquartile range), 172.70 (116.19, 286.42)] compared with non-diabetic subjects [92.09 (70.32, 147.24)] ( p 2 = 0.0689). Conclusion: A novel adipokine FAM19A5 was related to various metabolic and vascular risk factors in humans, suggesting its potential as a biomarker of cardio-metabolic disease.

ObjectiveLong-term glycemic variability has recently been recognized as another risk factor for future adverse health outcomes. We aimed to evaluate the risk of gestational diabetes mellitus (GDM) according to the prepregnancy long-term fasting plasma glucose (FPG) variability.Research design and methodsA total of 164 053 women who delivered their first baby between January 1, 2012 and December 31, 2015, were selected from the Korean National Health Insurance data. All women underwent at least three national health screening examinations, and the last examination should be conducted within 2 years before their first delivery. GDM was defined as the presence of more than four times of claim of GDM (International Classification of Disease, 10th Revision (ICD-10) O24.4 and O24.9) or prescription of insulin under the ICD-code of GDM. FPG variability was assessed by variability independent of the mean (FPG-VIM), coefficient of variation, SD, and average successive variability.ResultsAmong the 164 053 women, GDM developed in 6627 (4.04%). Those in the higher quartiles of FPG-VIM showed a stepwise increased risk of GDM. In fully adjusted model, the ORs for GDM was 1.22 (95% CI 1.14 to 1.31) in women with the highest FPG-VIM quartile compared with those in the lowest quartile. The risk for GDM requiring insulin therapy was 48% increase in women in the highest quartile of FPG-VIM compared with those in the lowest quartile, while that for GDM not requiring insulin therapy was 19% increase. The association between high FPG variability and the risk of GDM was intensified in the obese and aged more than 35 years women.ConclusionsIncreased FPG variability in the prepregnancy state is associated with the risk of GDM independent of confounding factors. Therefore, prepregnancy FPG variability might be a surrogate marker of the risk of GDM.

Background Diabetes mellitus is associated with an increased risk of dementia. We aimed to comprehensively analyze the incidence and risk factors for dementia and young-onset dementia (YOD) in diabetic patients in Korea using the National Health Insurance Service data. Methods Between January 1, 2009 and December 31, 2012, a total of 1,917,702 participants with diabetes were included and followed until the date of dementia diagnosis or until December 31, 2015. We evaluated the incidence and risk factors for all dementia, Alzheimer's disease (AD), and vascular dementia (VaD) by Cox proportional hazards analyses. We also compared the impact of risk factors on the occurrence of YOD and late-onset dementia (LOD). Results During an average of 5.1 years of follow-up, the incidence of all types of dementia, AD, or VaD was 9.5, 6.8, and 1.3/1,000 person-years, respectively, in participants with diabetes. YOD comprised 4.8% of all dementia occurrence, and the ratio of AD/VaD was 2.1 for YOD compared with 5.5 for LOD. Current smokers and subjects with lower income, plasma glucose levels, body mass index (BMI), and subjects with hypertension, dyslipidemia, vascular complications, depression, and insulin treatment developed dementia more frequently. Vascular risk factors such as smoking, hypertension, and previous cardiovascular diseases were more strongly associated with the development of VaD than AD. Low BMI and a history of stroke or depression had a stronger influence on the development of YOD than LOD. Conclusion The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus.

Prediabetic subjects represent a vulnerable population, requiring special care to reduce the risk of diabetes onset. We developed and validated a diabetes risk score for prediabetic subjects using the Korea National Diabetes Program (KNDP) cohort. Subjects included in the multicenter and prospective cohort (n = 1162) had high diabetes risk at baseline (2005) and were followed until 2012. Survival analysis was performed to analyze the prospective cohort over time, and the bootstrap method was used to validate our model. We confirmed our findings in an external cohort. A diabetes risk score was calculated and the cut-off defined using a receiver operating characteristic curve. Age, body mass index, total cholesterol, and family history of diabetes were associated with diabetes. The model performed well after correction for optimism (Cadj = 0.735). A risk score was defined with a cut-off of ≥5 that maximized sensitivity (72%) and specificity (62%), with an area under the curve of 0.73. Prediabetic subjects with a family history of diabetes had a higher probability of diabetes (risk score = 5) irrespective of other variables; this result was confirmed in the external cohort. Hence, prediabetic subjects with a family history of diabetes have a higher probability of developing diabetes, regardless of other clinical factors.

Study Objectives Although sleep duration and quality were significant risk factors of type 2 diabetes (T2D), the impact of sleep initiation time on the development of T2D has not been studied in large longitudinal studies. Methods A total of 3689 participants without diabetes aged 40–69 years at baseline were enrolled from the Korean Genome and Epidemiology Study and followed up for 12 years. Participants were categorized based on habitual sleep initiation time by questionnaire as follows: 20:00–22:59 (early sleepers, ES, n = 766), 23:00–00:59 (usual sleepers, US, n = 2407), and 1:00–5:59 (late sleepers, LS, n = 516). Incident T2D was identified biennially by fasting plasma glucose or 2-hour glucose after 75-g oral glucose loading or use of anti-diabetes medication. Results During follow-up, 820 cases of T2D were documented and the LS group showed the highest increase in insulin resistance. Hazard ratio (HR) (95% confidence interval) for T2D of LS compared to ES was 1.34 (1.04–1.74) after adjustment for covariates including sleep duration. The impact of late sleep on the development of T2D was more evident in older individuals (≥65 years at baseline) (HR = 4.24 [1.42–12.68] in older LS vs. older ES, HR = 1.27 [1.00–1.62] in younger LS vs. younger ES, pinteraction = 0.002). In addition, LS with low insulin secretion and sensitivity showed an approximately fivefold increased risk for T2D compared to ES with high insulin secretion and sensitivity. Conclusions/Interpretation Habitual late sleep initiation is a significant risk factor for T2D in Koreans, especially in people with lower insulin sensitivity, lower β-cell function, and older age.

Introduction: We investigated the annual incidence rate and risk factors for progression of diabetic retinopathy in The Korea National Diabetes Program. Method: The Korean national Diabetes Program (KNDP) is a prospective, multicenter, and observational cohort study performed on type 2 diabetic patients in Korea. The study started in May 20and continued to follow-up until March 2014. Of the 3,949 patients enrolled in the KNDP, we analyzed 2962 patients who had both eyes photographed and assessed at baseline and further follow-up. An ophthalmologist evaluated and graded the funduscopic findings. Diabetic reinopathy (DR) was classified as 4 stages which were no DR, NPDR, PDR and blindness. We calculated the annual incidence rate from stage to stage. We analyzed the risk factor for progression of diabetic retinopathy. Results: The mean follow-up time (SD) was 4.1 (1.7) years. The mean age and DM duration were 54.6 (9.8) years and 6.7 (6.5) years, respectively. The mean level of fasting glucose and HbA1c was 144 (50) mg/dl and 7.7 (1.7), respectively. Of those, patients with diabetic retinopathy was 691 (23.4%). The annual progression rate from no retinopathy to NPDR was 3.28% (295/2271). Patients progressed directly from NPDR to PDR at a rate of 3.13% (85/871). Three of 200 patients with PDR progressed to blindness, at an annual rate of 0.57%. Patients who further progressed retinopathy had older age, longer DM duration, higher levels of HbA1c, higher systolic blood pressure, and more history of cerebrovascular disease than those who didn’t progress retinopathy. Conclusion: We reported the results of larger scale on DR progression than previous study of Korea. When compared to previous studies, the disease progression has improved over the 2 decades in Korean patients with type 2 diabetes. Our findings are consistent with other recent small studies from Korea. This study also confirmed risk factors for DR progression. Disclosure H. Moon: None. J. Jeon: None. S. Lee: None. S. Han: None. H. Kim: None. K. Chun: None. T. Kim: None. Y. Kim: None. J. Woo: None. K. Ahn: None. M. Nam: None. S. Baik: None. Y. Park: None. K. Lee: None.

Background: Recent clinical evidences indicate that early rapid renal function decline is closely associated with the development of diabetic kidney disease. We have investigated the incidence and baseline clinical predictors of rapid renal function decline in patients with type 2 diabetes and normal baseline renal function. Methods: A total of 967 type 2 diabetic patients from the Korean National Diabetes Program (KNDP), a prospective, multicenter, observational cohort study, with serial GFR measurement for 5 years and normal renal function were included for the analysis. Rapid renal function decline was defined as an eGFR decline >3.3% per year. Carotid ultrasonography was used to assess carotid intima-media thickness (IMT) and the presence of plaque. Results: The mean age was 53.7 years with body mass index of 25.4 kg/m2. Rapid renal function decline developed in 158 participants (16.3%) and average GFR decline was -5.2 ± 1.9% /year in rapid decliners and -0.4 ± 1.9% /year in non-decliners. There were no differences in the presence of albuminuria or retinopathy between the rapid decliners and non-decliners at baseline. Multivariable logistic regression analyses revealed that female sex (odds ratio (OR) 4.80 [95% CI 2.69-8.56], p Conclusions: Our study suggests the need for close monitoring of renal function and early intensive management in patients with type 2 diabetes and carotid atherosclerosis. Disclosure D. Seo: None. S. Kim: None. S. Ahn: None. S. Hong: None. M. Nam: None. J. Woo: None. S. Baik: None. K. Lee: None. Y. Kim: None. Y. Park: None.

This study investigated the effects of diabetes and antidiabetic medications on the risk of pancreatic cancer(PaC). We extracted data on Koreans with newly diagnosed diabetes and selected age- and sex-matched controls provided by the National Health Insurance Corporation. Incident PaC was defined as a new registration in the Korea Central Cancer Registry under ICD-10 C25 with admission history until 2015. During 19,429,617.1 person-years, 8,589 PaCs were identified in 1,005,409 subjects for diabetes group and 4,021,636 subjects for control group. The diabetes group showed more than a two-fold risk for PaC compared with the control group. Among antidiabetic medications, metformin, thiazolidinedione, and dipeptidyl peptidase-4 inhibitor exposure was associated with decreased risk for future PaC(hazard ratio[95% confidence interval] = 0.86[0.77–0.96], 0.82[0.68–0.98], 0.57[0.51–0.64], respectively), whereas sulfonylurea and insulin exposure was related to increased risk(hazard ratio[95% CI] = 1.73[1.57–1.91], 2.86[1.43–5.74], respectively) compared to subjects with no drug exposure. Moreover, subjects with dual exposure history to metformin plus thiazolidinedione or metformin plus dipeptidyl peptidase-4 inhibitor had a lower risk of PaC compared to metformin-only treated subjects. In conclusion, Korean adults with diabetes are at higher risk of PaC compared with nondiabetic individuals, and this risk may be modified by antidiabetic medications.

Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p

Although sleep duration has been extensively studied in metabolic diseases, few studies have investigated the impact of sleep duration on chronic kidney disease. The aim of this study was to examine the relationship between sleep duration and albuminuria in the general population. Among 24,948 adults who participated in the 2011-2014 KNHANES, a total of 19,994 subjects were included in this analysis. Subjects were categorized into the following five groups according to self-reported sleep duration: less than 5 h, 6 h, 7 h, 8 h, and more than 9 h. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally. Subjects with both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with microalbuminuria (30-299 mg/g) and macroalbuminuria (≥300 mg/g) compared to those with a sleep duration of 7 hours. The U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, body mass index, smoking, alcohol, education, income, exercise, estimated glomerular filtration rate, diabetes mellitus, hypertension and hypercholesterolemia. The U-shaped association is more evident in the subgroup aged 65 or older, or in female subjects. Our findings suggest that both short and long sleep durations have a U-shaped association with UACR levels in the general population, independent of potential confounders.

BACKGROUND To estimate and compare the trends of all-cause and cause-specific mortality rates for subjects with and without diabetes in South Korea, from 2003 to 2013. METHODS Using a population-based cohort (2003 to 2013), we evaluated annual mortality rates in adults (≥30 years) with and without diabetes. The number of subjects in this analysis ranged from 585,795 in 2003 to 670,020 in 2013. RESULTS Age- and sex-adjusted all-cause mortality rates decreased consistently in both groups from 2003 to 2013 (from 14.4 to 9.3/1,000 persons in subjects with diabetes and from 7.9 to 4.4/1,000 persons in those without diabetes). The difference in mortality rates between groups also decreased (6.61 per 1,000 persons in 2003 to 4.98 per 1,000 persons in 2013). The slope associated with the mortality rate exhibited a steeper decrease in subjects with diabetes than those without diabetes (regression coefficients of time: -0.50 and -0.33, respectively; P=0.004). In subjects with diabetes, the mortality rate from cardiovascular disease decreased by 53.5% (from 2.73 to 1.27 per 1,000 persons, P for trend

This trial was conducted to compare the efficacy and safety of combination therapy with basal insulin glargine plus mitiglinide to that of basal insulin glargine plus voglibosein patients with type 2 diabetes. This was a 20-week, randomized, multicenter non-inferiority trial. Patients with HbA1c levels over 7.0% were randomly assigned to receive either mitiglinide (10 mg tid) or voglibose (0.2 mg tid) concurrent with insulin glargine for 16 weeks after a 4-week of basal insulin glargine monotherapy. The intention-to-treat population included 156 patients; 79 were placed in the mitiglinide group, and 77 were placed in the voglibose group. At 20 weeks, there was no significant difference between the mitiglinide group and the voglibose group in terms of the mean HbA1c level or the mean decrease of the HbAlc level from baseline (-0.9% [-7.5 mmol/mol] and -0.7%, [-5.3 mmol/mol] respectively). The mean fasting plasma glucose level and data of self-monitoring blood glucosewere significantly decreased from baseline to week 20 in both groups, but there was no significant difference between the two groups. The changes in the basal insulin requirements of each group were not significant. The prevalence of adverse events and the risk of hypoglycemia were similar for both groups. Combination therapy with mitiglinide plus basal insulin glargine was non-inferior to voglibose plus basal insulin glargine in terms of the effect on overall glycemic control.

Meteorin-like (Metrnl) was recently identified as a novel adipomyokine induced by exercise and cold exposure. Metrnl improves glucose tolerance, increases systemic energy expenditure, induces white adipose browning, and promotes anti-inflammatory gene programs in obese/diabetic mice. However, the relationship of Metrnl with diabetes and cardiometabolic risk variables in humans has not been explored.In 800 subjects (400 patients with type 2 diabetes and 400 non-diabetes), Metrnl concentration was measured with an enzyme-linked immunosorbent assay, and the correlations of Metrnl level with anthropometric parameters, lifestyle factors, body composition values, and laboratory measurements were assessed.Metrnl concentration was significantly higher in patients with diabetes than in those without diabetes [median (inter-quartile range); diabetes: 1219.9 (1020.6, 1535.6), non-diabetes: 1131.2 (993.1, 1313.6) pg/ml, P .001]. After adjustment for age and sex, Metrnl level was significantly associated with fasting plasma glucose, blood pressure, lipid profile, and eGFR, but not with BMI or percent body fat. Multiple stepwise regression analysis exhibited that Metrnl level was independently associated with diabetes status (P .001), eGFR (P .001), and total cholesterol (P = .026) (RThis study is the first to demonstrate that Metrnl level is elevated in human subjects with type 2 diabetes and is inversely related to various cardiometabolic risk factors, including renal function.

The prevalence and social burden of type 2 diabetes mellitus (T2DM) is increasing. Medication adherence is necessary for positive outcomes in patients with T2DM.This study evaluated the association between medication adherence and clinical/economic outcomes in patients with T2DM in the Republic of Korea over a 3-year period.This study used data from the Korean National Diabetes Program at 5 hospitals. Medication possession ratios of ≥90% and90% were used to define adherent and nonadherent groups, respectively. The degree of glycemic control, changes in blood pressure and lipid profiles, and health care costs were compared.Of the 608 patients, 472 were medication adherent and 136 were nonadherent. The adherent patients displayed improved fasting blood glucose and hemoglobin A1c during the study. Diastolic blood pressure and total cholesterol were lower at 36 months, and lower low-density lipoprotein cholesterol was noted at baseline and 24 months. The total health care costs were $1861, $2060, and $1924, respectively, versus $1617, $1751, and $1602 during the 3-year study period for the adherent group versus the nonadherent group, respectively (P = 0.316, 0.627, and 0.172, respectively), whereas the outpatient drug costs were $1143, $1176, and $1162 in the adherent group versus $925, $778, and $914 in the nonadherent group (P = 0.002, P0.001, and P = 0.001).The adherent patients displayed better glycemic control and lipid profiles. Medication-related expenses were higher in the adherent group, but overall health care costs, including hospitalization costs, were similar between the 2 groups.