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In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Background: We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database., Methods: Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference., Results: In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia., Conclusion: The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.

Background: To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline., Methods: We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018., Results: The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08-1.33), 1.27 (1.15-1.42), 1.39 (1.23-1.56), 1.69 (1.45-1.96), and 1.84 (1.49- 2.27) in very high-risk group, and 1.07 (1.02-1.13), 1.16 (1.10-1.21), 1.29 (1.22-1.36), 1.45 (1.36-1.55), and 1.73 (1.58-1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130-159, 160-189, and ≥190 mg/dL were 1.15 (1.11-1.20), 1.28 (1.22- 1.34), and 1.45 (1.36-1.54) in moderate-risk group and 1.07 (1.02-1.13), 1.20 (1.13-1.26), and 1.47 (1.37-1.57) in low-risk group., Conclusion: We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mg/dL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mg/dL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mg/dL is recommended.

Background/aims: The Korean Diabetes Association (KDA) guidelines recommend adults aged ≥ 40 years and adults aged ≥ 30 years with diabetes risk factors for diabetes screening. This study aimed to determine the age threshold for diabetes screening in Korean adults., Methods: This study was based on the analyses of Korean adults aged ≥ 20 years using the Korea National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service-National Sample Cohort (NHIS-NSC). To evaluate screening effectiveness, we calculated the number needed to screen (NNS)., Results: NNS to detect diabetes decreased from 63 to 34 in the KNHANES and from 71 to 42 in the NHIS-NSC between the ages of 30-34 and 35-39. When universal screening was applied to adults aged ≥ 35, the NNS was similar to that of adults aged ≥ 40. Compared to the KDA guidelines, the rate of missed screening positive in adults aged ≥ 20 decreased from 4.0% to 0.2% when the newly suggested screening criteria were applied., Conclusion: Universal screening for adults aged ≥ 35 and selective screening for adults aged 20 to 34, considering diabetes risk factors, may be appropriate for detecting prediabetes and diabetes in South Korea.

Background: There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data., Methods: Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018., Results: The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL., Conclusion: For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

Diabetes mellitus is a major risk factor for the development of heart failure. Furthermore, the prognosis of heart failure is worse in patients with diabetes mellitus than in those without it. Therefore, early diagnosis and proper management of heart failure in patients with diabetes mellitus are important. This review discusses the current criteria for diagnosis and screening tools for heart failure and the currently recommended pharmacological therapies for heart failure. We also highlight the effects of anti-diabetic medications on heart failure.

Diabetes screening serves to identify individuals at high-risk for diabetes who have not yet developed symptoms and to diagnose diabetes at an early stage. Globally, the prevalence of diabetes is rapidly increasing. Furthermore, obesity and/or abdominal obesity, which are major risk factors for type 2 diabetes mellitus (T2DM), are progressively increasing, particularly among young adults. Many patients with T2DM are asymptomatic and can accompany various complications at the time of diagnosis, as well as chronic complications develop as the duration of diabetes increases. Thus, proper screening and early diagnosis are essential for diabetes care. Based on reports on the changing epidemiology of diabetes and obesity in Korea, as well as growing evidence from new national cohort studies on diabetes screening, the Korean Diabetes Association has updated its clinical practice recommendations regarding T2DM screening. Diabetes screening is now recommended in adults aged ≥35 years regardless of the presence of risk factors, and in all adults (aged ≥19) with any of the risk factors. Abdominal obesity based on waist circumference (men ≥90 cm, women ≥85 cm) was added to the list of risk factors.

Background: To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM)., Methods: Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims., Results: Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF., Conclusion: The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p'-DDE, and p,p'-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p'-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (β = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (β = 0.032, p = 0.040) and males aged ≥50 (β = -0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (G D ). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p'-DDE, p,p'-DDT, and Factor 1 were positively associated with G D, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with G D and total T3 in males aged ≥50. BDE-47 and β-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and G D ., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent., Methods: This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT)., Results: Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25 kg/m 2 ), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations., Conclusions: Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Environmental pollutants have been known to increase the risks of not only respiratory and cardiovascular disease but also metabolic diseases such as obesity and diabetes mellitus (DM). Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) such as benzene and toluene are major constituents of environmental pollution. In the present study, we employed the population of the Korean National Environmental Health Survey (KoNEHS) Cycle 3 conducted between 2015 and 2017, and assessed the associations of urinary biomarkers for PAHs and VOCs exposure with obesity and DM. A total of 3787 adult participants were included and the urinary concentrations of four PAH metabolites and two VOC metabolites were measured. For correcting urine dilution, a covariate-adjusted standardization method was used. The highest quartiles of urinary 2-hydroxynaphthalene (2-NAP) [OR (95% confidence interval (CI)) = 1.46 (1.13, 1.87)] and sum of PAH metabolites [OR (95% CI) = 1.45 (1.13, 1.87)] concentrations were associated with a higher risk of obesity [body mass index (BMI)≥25 kg/m 2 ]. BMI was positively associated with urinary 2-NAP [β (95% CI) = 0.25 (0.09, 0.41), p = 0.003] and sum of PAH metabolites [β (95% CI) = 0.29 (0.08, 0.49), p = 0.006] concentrations. The risk of DM was increased with increasing quartile of 2-hydroxyfluorene (2-OHFlu) and trans, trans-muconic acid (t,t-MA) (p for trend<0.05 and < 0.001, respectively). The highest quartile of t,t-MA showed a significantly higher risk of DM [OR (95% CI) = 2.77 (1.74, 4.42)] and obesity [OR (95% CI) = 1.42 (1.06, 1.90)]. Urinary t,t,-MA level was positively associated with BMI [(β (95% CI) = 0.51 (0.31, 0.71), p < 0.001] and non-alcoholic fatty liver disease index [(β (95% CI) = 0.09 (0.06, 0.12), p < 0.001]. In conclusion, the benzene metabolites t,t-MA and PAH metabolite 2-OHFlu were associated with an increased risk of DM. Urinary biomarkers for PAHs and VOCs were positively associated with BMI in the Korean adult population. Further studies to validate these observations in other populations are warranted., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The independent effect of serum triglyceride levels on the development of ischemic cardiovascular disease (CVD) remains inconclusive, which might be due to heterogeneity among study populations., Objective: To evaluate the effect of triglyceride levels on ischemic CVD and mortality in Korean women, with stratification according to the menopausal status, diabetes mellitus, or low-density lipoprotein cholesterol levels (LDL-C)., Methods: We retrospectively investigated Korean women aged 40-69 years who underwent health examination in 2009 and were followed up until 2018 using nationwide claim data. The subjects were divided according to triglyceride quartiles (Q): Q1 <70 mg/dL, Q2 71-99 mg/dL, Q3 100-142 mg/dL, and Q4 ≥143 mg/dL. The primary outcome was the incidence of CVD defined as a composite of myocardial infarction and ischemic stroke., Results: Among 2,208,347 women, primary outcome occurred in 62,255 (2.8%) subjects. As triglyceride levels increased, the event rate of primary outcome increased in both premenopausal and postmenopausal women in the fully adjusted model (hazard ratio [HR] per 1 Q, 1.10 [95% confidence interval (CI), 1.08-1.12] and 1.08 [95% CI, 1.07-1.09], respectively), which was maintained on further stratification according to diabetes or LDL-C (P<0.05 in all). Higher triglyceride levels were more significantly associated with the primary outcome, MI, and stroke risk among women with optimal non-high-density lipoprotein cholesterol levels (non-HDL-C) <130 mg/dL, but only weakly with stroke for women with non-optimal non-HDL-C., Conclusion: Triglyceride is an independent prognosticator in the development of ischemic CVD in Korean women aged 40-69 years., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Background: We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines., Methods: This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe., Results: Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy., Conclusion: According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

Background: Limited information is available about the present characteristics and dynamic clinical changes that occur in patients with COVID-19 during the early phase of the illness., Objective: This study aimed to develop and validate machine learning models based on clinical features to assess the risk of severe disease and triage for COVID-19 patients upon hospital admission., Methods: This retrospective multicenter cohort study included patients with COVID-19 who were released from quarantine until April 30, 2020, in Korea. A total of 5628 patients were included in the training and testing cohorts to train and validate the models that predict clinical severity and the duration of hospitalization, and the clinical severity score was defined at four levels: mild, moderate, severe, and critical., Results: Out of a total of 5601 patients, 4455 (79.5%), 330 (5.9%), 512 (9.1%), and 301 (5.4%) were included in the mild, moderate, severe, and critical levels, respectively. As risk factors for predicting critical patients, we selected older age, shortness of breath, a high white blood cell count, low hemoglobin levels, a low lymphocyte count, and a low platelet count. We developed 3 prediction models to classify clinical severity levels. For example, the prediction model with 6 variables yielded a predictive power of >0.93 for the area under the receiver operating characteristic curve. We developed a web-based nomogram, using these models., Conclusions: Our prediction models, along with the web-based nomogram, are expected to be useful for the assessment of the onset of severe and critical illness among patients with COVID-19 and triage patients upon hospital admission., (©Bumjo Oh, Suhyun Hwangbo, Taeyeong Jung, Kyungha Min, Chanhee Lee, Catherine Apio, Hyejin Lee, Seungyeoun Lee, Min Kyong Moon, Shin-Woo Kim, Taesung Park. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 16.04.2021.)

Aims: To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM., Methods: This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy., Results: Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007)., Conclusions: DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG., Trial Registration: ClinicalTrials.gov (NCT03062072)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Phthalates and bisphenol A (BPA) have been suspected as risk factors for obesity and diabetes mellitus (DM) among humans. However, associations between phthalates and environmental phenols are often inconsistent across different populations. In this study, we recruited the adult population (n = 3782) of the Korean National Environmental Health Survey (KoNEHS) 2015-2017 (Cycle 3) and assessed the associations between urinary biomarkers of phthalate, BPA, and paraben exposure with obesity and DM. A potential collider issue with the use of urinary creatinine (Cr) or specific gravity (SG) exists when adjusting urinary dilution; therefore, a covariate-adjusted standardization (CAS) was employed for adjustment, and the results were compared. In the present population, the direction of the association often varied depending on the choices made to adjust urinary dilution. When using CAS, the direction of association resembled those of previously reported experimental observations. With Cr or SG adjustment, ORs for obesity decreased in the highest quartiles of monocarboxyoctyl phthalate (MCOP) [OR (95% CI) = Cr: 0.71 (0.54, 0.93); SG: 0.68 (0.52, 0.90)], monocarboxy-isononyl phthalate (MCNP) [OR (95% CI) = Cr: 0.67 (0.52, 0.87); SG: 0.68 (0.52, 0.89)], and mono(3-carboxylpropyl) phthalate (MCPP) in the urine [OR (95% CI) = Cr: 0.60 (0.47, 0.76); SG: 0.61 (0.48, 0.77)]; however, with CAS, these negative associations disappeared. Instead, mono-benzyl phthalate (MBzP) [OR (95% CI) = 1.31 (1.03, 1.66)], BPA [OR (95% CI) = 1.62 (1.27, 2.06)], or ethyl paraben (EtP) [OR (95% CI) = 1.51 (1.19, 1.91)] concentrations in the highest quartile showed positive associations with a higher risk of obesity. On the other hand, for DM, an overall decrease in ORs was observed for phthalate metabolites and BPA following SG adjustment and disappeared with CAS adjustment. In addition, the highest quartiles of BPA, methyl paraben (MeP), and ethyl paraben (EtP) showed a significantly higher risk of DM than those in the lowest quartiles following CAS [OR (95% CI) = BPA: 1.65 (1.06, 2.59); MeP: 1.68 (1.08, 2.60); and EtP: 2.74 (1.77, 4.24), respectively]. The present observations outline the importance of using an appropriate adjustment method for urinary dilution in association studies on obesity and DM. In addition, several phthalates, BPA, and parabens were identified as potential chemical risk factors for these outcomes. Further studies are warranted in other populations to confirm these observations., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with non-alcoholic fatty liver disease (NAFLD) using a nationwide cross-sectional survey., Methods: Individuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (N = 14 861), with sample weights applied. Muscle strength was quantified as the handgrip strength divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q 1 ) of the handgrip strength/BMI for our sample population. NAFLD was defined as hepatic steatosis index >36. Advanced fibrosis was defined as a fibrosis-4 index score ≥1.30 (Fibrosis FIB4 )., Results: The mean age of the study population was 45.6 ± 0.2 years, and 42.4% were male. As muscle strength increased, the mean BMI and age decreased accordingly, and the proportions of diabetes, dyslipidaemia, hypertension, and obesity decreased significantly (P < 0.001 for all). In a crude analysis, the LMS was associated with an increased prevalence of NAFLD (odds ratio [OR] 3.62, 95% confidence interval [CI] 3.25-4.03, P < 0.001), which remained significant even after adjustment for age, sex, obesity, insulin resistance, diabetes, hypertension, dyslipidaemia, and high-sensitivity C-reactive protein (OR 1.66, 95% CI 1.28-2.16, P < 0.001). In this logistic regression model, the prevalence of NAFLD decreased by 24% with each quartile increment in muscle strength (OR 0.76, 95% CI 0.68-0.85, P < 0.001). Among individuals with NAFLD (n = 2092), LMS was significantly associated with the presence of advanced fibrosis (Fibrosis FIB4 ) independently of age, sex, obesity, diabetes, hypertension, dyslipidaemia, and high-sensitivity C-reactive protein (OR 1.66, 95% CI 1.01-2.49, P = 0.015), which lost its statistical significance after additional adjustment for insulin resistance., Conclusions: Low muscle strength is independently associated with NAFLD. The significant association between LMS and advanced fibrosis in NAFLD may be mediated through insulin resistance., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodium-glucose cotransporter-2 (SGLT2) inhibitor showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2 inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend the long-term use SGLT2 inhibitor in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendation due to lack of long-term clinical trials testing reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after publication of several large-scale renal outcome trials., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Diabetes Association.)

Background: To investigate the performance of the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) in a large, prospective, community-based cohort in Korea and to compare it with that of the Framingham Global Cardiovascular Disease Risk Score (FRS-CVD) and the Korean Risk Prediction Model (KRPM)., Methods: In the Korean Genome and Epidemiology Study (KOGES)-Ansan and Ansung study, we evaluated calibration and discrimination of the PCE for non-Hispanic whites (PCE-WH) and for African Americans (PCE-AA) and compared their predictive abilities with the FRS-CVD and the KRPM., Results: The present study included 7,932 individuals (3,778 men and 4,154 women). The PCE-WH and PCE-AA moderately overestimated the risk of atherosclerotic cardiovascular disease (ASCVD) for men (6% and 13%, respectively) but underestimated the risk for women (-49% and -25%, respectively). The FRS-CVD overestimated ASCVD risk for men (91%) but provided a good risk prediction for women (3%). The KRPM underestimated ASCVD risk for men (-31%) and women (-31%). All the risk prediction models showed good discrimination in both men (C-statistic 0.730 to 0.735) and women (C-statistic 0.726 to 0.732). Recalibration of the PCE using data from the KOGES-Ansan and Ansung study substantially improved the predictive accuracy in men., Conclusion: In the KOGES-Ansan and Ansung study, the PCE overestimated ASCVD risk for men and underestimated the risk for women. The PCE-WH and the FRS-CVD provided an accurate prediction of ASCVD in men and women, respectively., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Diabetes Association.)

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

Aim: We investigated the effects of metformin on cognitive function in a prospective cohort of older adults., Methods: Participants aged ≥60 years were selected, and their Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment, including the Mini-Mental State Examination, and activities of daily living were evaluated prospectively. Rapid deterioration of cognitive function was defined as annual change of test scores in the lowest quartile., Results: A total of 732 participants (mean age 76.7 ± 6.6 years) were followed up for 2.9 years (interquartile range 1.0-5.7 years). A linear mixed model showed that diabetes was associated with significant deterioration of Verbal Delayed Free Recall and Recognition scores (P = 0.007 and 0.022, respectively). Among diabetes patients, metformin treatment was not associated with changes of any Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component or activities of daily living index. However, rapid deterioration of Mini-Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin-taking group, even after adjustment for age, sex, education level, baseline cognitive function, baseline glycated hemoglobin levels, renal and liver function, body mass index, hypertension, dyslipidemia, antidiabetic agents other than metformin, and baseline brain imaging abnormality (odds ratio 4.47, 95% confidence interval 1.24-16.05 and odds ratio 7.37, 95% confidence interval 1.19-45.56)., Conclusions: Metformin treatment was not associated with changes of any of Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component scores or activities of daily living index. However, rapid deterioration of Mini-Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin-treated group. Geriatr Gerontol Int 2019; 19: 755-761., (© 2019 Japan Geriatrics Society.)

We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants, PAX4 Arg192His increased risk of T2D and GLP1R Arg131Gln decreased risk of T2D in genome-wide significance (odds ratio [OR] 1.48, P = 4.47 × 10 -16 and OR 0.84, P = 3.55 × 10 -8 , respectively). Another variant at PAX4 192 codon Arg192Ser was nominally associated with T2D (OR 1.62, P = 5.18 × 10 -4 ). In T2D patients, PAX4 Arg192His was associated with earlier age at diagnosis, and GLP1R Arg131Gln was associated with decreased risk of cardiovascular disease. In control subjects without diabetes, the PAX4 Arg192His was associated with higher fasting glucose and GLP1R Arg131Gln was associated with lower fasting glucose and HbA 1c level. Gene-based analysis revealed that SLC30A8 was most significantly associated with decreased risk of T2D ( P = 1.0 × 10 -4 ). In summary, we have identified nonsynonymous variants associated with risk of T2D and related phenotypes in Koreans., (© 2018 by the American Diabetes Association.)

Background: We investigated the change in the relative impact of a family history of diabetes (FH) and abdominal obesity on diabetes mellitus (DM) over a 10-year period in Korea., Methods: We analyzed data from the 2001, 2005, and 2010 Korean National Health and Nutrition Examination Survey that were weighted to represent the entire Korean population in each year. Multiple logistic regression analysis was used to examine the association between DM and FH or abdominal obesity., Results: In men aged 30-49 years, the association between FH and DM was stronger in 2010 than in 2001; the odds ratio (OR) was 1.508 (95% confidence interval [CI], 0.814-2.792) in 2001, 3.351 (95% CI, 1.599-7.024) in 2005, and 7.302 (95% CI, 3.451-15.451) in 2010 (P for trend = 0.003). In contrast, the association between abdominal obesity and DM was weaker in 2010 (OR, 0.969 [95% CI, 0.465-2.018]) than in 2001 (OR, 2.532 [95% CI, 1.572-4.080]) (P for trend = 0.037). In women aged 30-49 years, there was no significant change in OR of FH or abdominal obesity during the same period. (P for trend = 0.367 and 0.401, respectively)., Conclusions: In Korean men aged 30-49 years, the association between FH and DM has been stronger from 2001 to 2010, whereas abdominal obesity was less important in 2010 compared to 2001., (© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: Serum high-density lipoprotein cholesterol (HDL-C) has been reported to be lower in Asians than in Caucasians., Objective: We compared HDL-C levels between the Korean and US populations using stratified analysis according to age and sex and estimated the optimal cutoff value for HDL-C that best predicts the risk of cerebrovascular accidents (CVAs) and ischemic heart disease (IHD) in Koreans., Methods: The Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012 and the National Health and Nutrition Examination Survey (NHANES) 2011-2012 were used for the Korean and US populations, respectively. HDL-C levels were compared using general linear models. To estimate the optimal HDL-C cutoff value that predicts CVAs and IHD, sensitivity and specificity of different HDL-C levels were calculated., Results: The mean HDL-C level was significantly lower in KNHANES in both sexes (46.1 [standard error, 0.2] mg/dL in KNHANES and 47.7 [0.5] mg/dL in NHANES, P = .003 in men, and 51.2 [0.2] mg/dL in KNHANES and 58.3 [0.8] mg/dL in NHANES, P < .001 in women). The optimal HDL-C cutoff to predict CVA-IHD was 43 mg/dL and 48 mg/dL for Korean men and women, respectively, and 41 mg/dL and 56 mg/dL for US men and women, respectively., Conclusion: HDL-C levels are significantly lower in both sexes in the Korean population than the US population. The optimal cutoff HDL-C value to predict the risk of CVA-IHD was 43 mg/dL for men and 48 mg/dL for women in the Korean population., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus., Methods: We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea., Results: Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 - 1.998)., Conclusions: The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out.