Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population. Methods: Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs. Results: A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34–3.18, 4.74±3.57 and 1.14–8.33, and 4.85±3.58 and 1.25–8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels. Conclusion The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.

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

OBJECTIVES: Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. METHODS: We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. RESULTS: In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24). CONCLUSIONS Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals. Materials and Methods: Adults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively).Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND 50 ) >10 was considered indicative of protective NAb titers. Results: In total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 -193), and 182 (175 - 198) days after the second dose. Overall, ND 50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND 50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P= 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND 50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99). Conclusion A third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2.

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

OBJECTIVES: Our study examined the dose-response relationship between smoking amounts (pack-years) and the risk of developing pancreatic cancer in Korean men. METHODS: Of 125,743 participants who underwent medical health checkups in 2009, 121,408 were included in the final analysis and observed for the development of pancreatic cancer. We evaluated the associations between smoking amounts and incident pancreatic cancer in 4 groups classified by pack-year amounts. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of incident pancreatic cancer by comparing groups 2 (<20 pack-year smokers), 3 (20-≤40 pack-year smokers), and 4 (>40 pack-year smokers) with group 1 (never smokers). RESULTS: During 527,974.5 person-years of follow-up, 245 incident cases of pancreatic cancer developed between 2009 and 2013. The multivariate-adjusted HRs (95% CIs) for incident pancreatic cancer in groups 2, 3, and 4 were 1.05 (0.76 to 1.45), 1.28 (0.91 to 1.80), and 1.57 (1.00 to 2.46), respectively (p for trend=0.025). The HR (95% CI) of former smokers showed a dose-response relationship in the unadjusted model, but did not show a statistically significant association in the multivariate-adjusted model. The HR (95% CI) of current smokers showed a dose-response relationship in both the unadjusted (p for trend=0.020) and multivariate-adjusted models (p for trend=0.050). CONCLUSIONS The risk of developing pancreatic cancer was higher in current smokers status than in former smokers among Korean men, indicating that smoking cessation may have a protective effect.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. Conclusion The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to deter-mine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

PURPOSE: The prevalence and burden of asthma is increasing worldwide. In this study, we analyzed 3 different Korean national health survey datasets to determine the general features of adult asthma in Korea and to obtain basic information that would support future strategies for better management of adult asthma. METHODS: The surveys used in this study included the Korea National Health and Nutrition Examination Survey (KNHANES), Korea Community Health Survey (KCHS) and National Health Insurance Service-National Sample Cohort (NHIS-NSC). We investigated annual asthma prevalence, evaluating the rate and risk factors of asthma exacerbation by age and sex, and clinical data of 1,832 patients with asthma who were registered in the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) were analyzed to elucidate risk factors for asthma exacerbation. We also analyzed another asthma cohort and added it as replication data. RESULTS: In the KNHANES database, annual asthma prevalence rates varied from 1.2% to 3.1%. In the KCHS database, overall prevalence increased, with significant regional differences (1.6%–2.1%). The NHIS-NSC indicated a gradual increase in annual asthma prevalence from 4.5% to 6.2%. Interestingly, all 3 surveys indicated the highest prevalence of asthma among elderly women. In addition, elderly women with asthma had a significantly higher risk of asthma exacerbation (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.19–2.93; P=0.006). Approximately 11% of patients were classified as having severe asthma. An asthma cohort analysis identified female sex, low baseline pulmonary function, longer treatment duration, high variability in pulmonary function and significant changes in Asthma Control Test scores as risk factors for asthma exacerbation. CONCLUSIONS: The prevalence of asthma in Korea is consistently high among elderly and female populations. These results should lay the foundation for strategies for effective asthma prevention and management; elderly female patients with asthma should receive particular attention.
Adult* ; Aged* ; Asthma* ; Cohort Studies* ; Dataset ; Female ; Health Surveys ; Humans ; Incidence ; Korea ; National Health Programs ; Nutrition Surveys ; Prevalence* ; Risk Factors