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Abstract Background and aims The association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is unclear. This study aimed to investigate the impact of spectrum of SLD on the risk of heart failure and cardiovascular (CV) mortality in patients with T2DM. Methods In a nationwide cohort study, 2,745,689 adults with T2DM were followed from 2009 to 2012 until 2018. Participants were categorized into no steatotic liver disease (no SLD) and SLD groups. The SLD group was stratified based on metabolic risk factors, alcohol consumption and viral hepatitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for heart failure (HF) and CV mortality risk. Results The prevalence of MASLD, metabolic alcohol-associated liver disease (MetALD), alcohol-associated liver disease with metabolic dysfunction (ALD with MD) and MASLD with viral hepatitis (VH) was 49.6%, 7.2%, 2.3%, and 2.0%. Individuals with MASLD (adjusted HR [aHR], 1.11), MetALD (aHR, 1.14), ALD with MD (aHR, 1.32) and MASLD with VH (aHR, 1.12) had a higher risk of developing HF compared with the no SLD group. The risk of CV mortality was also increased in those with SLD groups compared to those with no SLD. The risk of new-onset HF and CV mortality showed a J-shaped association with alcohol consumption regardless of SLD status. Conclusion SLD is independent risk factor of new-onset HF and CV mortality in persons with T2DM, and alcohol consumption has a J-shaped association with risk of HF and CV mortality, regardless of SLD status.

This study aimed to compare the changes in the bioactivities of peptide extracts (< 10 kDa) obtained from Jeju black pigs (JBP) and three-way crossbred pigs (Landrace × Yorkshire × Duroc, LYD) before and after digestion. The results showed that the loin peptide extracts of JBP maintained high 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity after in vitro digestion. However, the iron chelating activity and antihypertensive activity of all peptide extracts were decreased. This study suggested that the peptide extracts produced through alkaline-AK digestion have sufficiently high antioxidant and antihypertensive activities; however, these activities were reduced after in vitro digestion. Meanwhile, the JBP loin and ham peptide extracts promoted high superoxide dismutase (SOD) activity than that of LYD when administered to mice. Furthermore, the ham peptide extracts of JBP showed a relatively high antihypertensive activity in mice. Therefore, it is deemed that these peptide extracts from JBP are more bioactive than that of LYD, and can be used as bioactive materials.

Abstract Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78–1.85 ng/dL) and triiodothyronine (T3, 76–190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels 50% and (a) E/e’ ratio > 15, or (b) E/e’ ratio of 8–15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01–1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Background This study investigated the optimal coefficient of variance (%CV) for preventing hypoglycemia based on real-time continuous glucose monitoring (rt-CGM) data in people with type 1 diabetes mellitus (T1DM) already achieving their mean glucose (MG) target. Methods Data from 172 subjects who underwent rt-CGM for at least 90 days and for whom 439 90-day glycemic profiles were available were analyzed. Receiver operator characteristic analysis was conducted to determine the cut-off value of %CV to achieve time below range (%TBR)< 54mg/dL 135 mg/dL, and ≤135 mg/dL, respectively. The cut-off value for %TBR< 54mg/dL=0% was 29.2% in MG ≤135 mg/dL. In profiles with MG ≤135 mg/dL, 94.2% of profiles with a %CV 135 mg/dL, 99.4% of profiles with a %CV

Abstract Background We investigated the effects of a physical activity encouragement intervention based on a smartphone personal health record (PHR) application (app) on step count increases, glycemic control, and body weight in patients with type 2 diabetes (T2D). Methods In this 12-week, single-center, randomized controlled, 12-week extension study, patients with T2D who were overweight or obese were randomized using ratio 1:2 to a group using a smartphone PHR app (control group) or group using the app and received individualized motivational text messages (intervention group) for 12 weeks. During the extension period, the sending of the encouraging text messages to the intervention group was discontinued. The primary outcome was a change in daily step count after 12 weeks and analyzed by independent t-test. The secondary outcomes included HbA1c, fasting glucose, and body weight analyzed by paired or independent t-test. Results Of 200 participants, 62 (93.9%) and 118 (88.1%) in the control and intervention group, respectively, completed the 12-week main study. The change in daily step count from baseline to week 12 was not significantly different between the two groups (P = 0.365). Among participants with baseline step counts

Background Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. Methods A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. Results Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. Conclusion The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Background We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). Methods For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). Results During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. Conclusion Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Islet transplantation is the most effective treatment strategy for type 1 diabetes. Long-term storage at ultralow temperatures can be used to prepare sufficient islets of good quality for transplantation. For freezing islets, dimethyl sulfoxide (DMSO) is a commonly used penetrating cryoprotective agent (CPA). However, the toxicity of DMSO is a major obstacle to cell cryopreservation. Hydroxyethyl starch (HES) has been proposed as an alternative CPA. To investigate the effects of two types of nonpermeating CPA, we compared 4 % HES 130 and HES 200 to 10 % DMSO in terms of mouse islet yield, viability, and glucose-stimulated insulin secretion (GSIS). After one day of culture, islets were cryopreserved in each solution. After three days of cryopreservation, islet recovery was significantly higher in the HES 130 and HES 200 groups than in the DMSO group. Islet viability in the HES 200 group was also significantly higher than that in the DMSO group on Day 1 and Day 3. Stimulation indices determined by GSIS were higher in the HES 130 and 200 groups than in the DMSO group on Day 3. After three days of cryopreservation, HES 130 and HES 200 both reduced the expression of apoptosis- and necrosis-associated proteins and promoted the survival of islets. In conclusion, the use of HES as a CPA improved the survival and insulin secretion of cryopreserved islets compared with the use of a conventional CPA.

Abstract We aimed to determine the association between cholesterol values and the risk of all-cause mortality in newly diagnosed patients with cancer in a large-scale longitudinal cohort. Newly diagnosed patients with cancer were reviewed retrospectively. Cox proportional hazards regression models determined the association between baseline levels of total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and the risk of all-cause mortality. A restricted cubic spline curve was used to identify the association between total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol with the risk of death on a continuous scale and to present the lowest values of lipid measurements associated with death. The median follow-up duration of the study was 5.77 years. Of the 59,217 patients with cancer, 12,624 patients were expired. The multivariable adjusted hazard ratio (aHR) for all-cause mortality in patients with cancer with 1st–5th (≤ 97 mg/dL) and 96th–100th (> 233 mg/dL) in TC levels was 1.54 (95% CI 1.43–1.66) and 1.28 (95% CI 1.16–1.41), respectively, compared to 61st–80th (172–196 mg/dL). The TC level associated with the lowest mortality risk in the multivariable model was 181 mg/dL. In comparison with LDL-C levels in the 61st–80th (115–136 mg/dL), the multivariable aHR for all-cause mortality in cancer patients with LDL-C levels in the 1st-5th (≤ 57 mg/dL) and 96th–100th (> 167 mg/dL) was 1.38 (95% CI 1.14–1.68) and 0.94 (95% CI 0.69–1.28), respectively. The 142 mg/dL of LDL cholesterol showed the lowest mortality risk. We demonstrated a U-shaped relationship between TC levels at baseline and risk of mortality in newly diagnosed patients with cancer. Low LDL levels corresponded to an increased risk of all-cause death.

Abstract The association of bipolar disorder (BD) with the risk of cardiometabolic diseases and premature death in Asians needs to be further determined. Relatively less attention has been paid to heart failure (HF) among cardiometabolic outcomes. We analyzed the Korean National Health Insurance Service database (2002–2018) for this population-based, matched cohort study. The hazards of ischemic stroke, ischemic heart disease (IHD), hospitalization for HF (hHF), composite cardiometabolic diseases, and all-cause mortality during follow-up were compared between individuals with BD (n = 11,329) and 1:1-matched controls without psychiatric disorders among adults without cardiometabolic disease before or within 3 months of baseline. Hazards of outcomes were higher in individuals with BD than in matched controls (adjusted hazard ratios [95% confidence intervals]: 1.971 [1.414–2.746] for ischemic stroke, 1.553 [1.401–1.721] for IHD, 2.526 [1.788–3.567] for hHF, 1.939 [1.860–2.022] for composite cardiometabolic diseases, and 2.175 [1.875–2.523] for all-cause mortality) during follow-up. Associations between BD and outcome hazards were more prominent in younger individuals (p for interaction

Background The effects of psychotic disorders on cardiometabolic diseases and premature death need to be determined in Asian populations. Methods In this population-based matched cohort study, the Korean National Health Insurance Service database (2002 to 2018) was used. The risk of type 2 diabetes mellitus (T2DM), acute myocardial infarction (AMI), ischemic stroke, composite of all cardiometabolic diseases, and all-cause death during follow-up was compared between individuals with psychotic disorders treated with antipsychotics (n=48,162) and 1:1 matched controls without psychiatric disorders among adults without cardiometabolic diseases before or within 3 months after baseline. Results In this cohort, 53,683 composite cases of all cardiometabolic diseases (during median 7.38 years), 899 AMI, and 1,216 ischemic stroke cases (during median 14.14 years), 7,686 T2DM cases (during median 13.26 years), and 7,092 deaths (during median 14.23 years) occurred. The risk of all outcomes was higher in subjects with psychotic disorders than matched controls (adjusted hazard ratios [95% confidence intervals]: 1.522 [1.446 to 1.602] for T2DM; 1.455 [1.251 to 1.693] for AMI; 1.568 [1.373 to 1.790] for ischemic stroke; 1.595 [1.565 to 1.626] for composite of all cardiometabolic diseases; and 2.747 [2.599 to 2.904] for all-cause mortality) during follow-up. Similar patterns of associations were maintained in subgroup analyses but more prominent in younger individuals (P for interaction

Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

The purpose of this study was to investigate the recent development of meat analog, industrialization, and the related legal changes worldwide. Summarizing the current status of the industrialization of meat analog, studies on plant-based meat, mycoprotein, and edible insects were mainly conducted to investigate their sensory properties (texture, taste, flavor, and color resembling meat), nutritional and safety evaluations, acquisition method of meat alternatives, and commercialization. Cultured meat is mainly studied for developing muscle satellite cell acquisition and support techniques or materials for the formation of structures. However, these technologies have not reached the level for active industrialization. Even though there are differences in the food categories and labeling between countries, it is common to cause confusion or to relay false information to consumers; therefore, it is important to provide accurate information. In this study, there were some differences in the food classification and food definition (labeling) contents for each country and state depending on the product shape or form, raw materials, and ingredients. Therefore, this study can provide information about the current research available on meat alternatives, improve regulation, and clarify laws related to the meat analog industry, which can potentially grow alongside the livestock industry.

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 explored the risk of death from pneumonia according to cumulative duration in low household income state (LHIS) among adults with type 2 diabetes mellitus (T2DM). Methods Using Korean National Health Insurance Service data (2002 to 2018), the hazards of mortality from pneumonia were analyzed according to duration in LHIS (being registered to Medical Aid) during the 5 years before baseline (0, 1–4, and 5 years) among adults with T2DM who underwent health examinations between 2009 and 2012 (n=2,503,581). Hazards of outcomes were also compared in six groups categorized by insulin use and duration in LHIS. Results During a median 7.18 years, 12,245 deaths from pneumonia occurred. Individuals who had been exposed to LHIS had higher hazards of death from pneumonia in a dose-response manner (hazard ratio [HR], 1.726; 95% confidence interval [CI], 1.568 to 1.899 and HR, 4.686; 95% CI, 3.948 to 5.562 in those exposed for 1–4 and 5 years, respectively) compared to the non-exposed reference. Insulin users exposed for 5 years to LHIS exhibited the highest outcome hazard among six groups categorized by insulin use and duration in LHIS. Conclusion Among adults with T2DM, cumulative duration in LHIS may predict increased risks of mortality from pneumonia in a graded dose-response manner. Insulin users with the longest duration in LHIS might be the group most vulnerable to death from pneumonia among adults with T2DM.

Abstract We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4–8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

Background This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

BackgroundPrevious studies have reported that depression can increase the risk of type 2 diabetes. However, they did not sufficiently consider antidepressants or comorbidity.MethodsThe National Health Insurance Sharing Service database was used. Among the sample population, 276,048 subjects who had been diagnosed with depression and prescribed antidepressants (DEP with antidepressants group) and 79,119 subjects who had been diagnosed with depression but not prescribed antidepressants (DEP without antidepressants group) were found to be eligible for this study. Healthy controls (HCs) were 1:1 matched with the DEP with antidepressants group for age and sex. We followed up with them for the occurrence of type 2 diabetes.ResultsIn the group of DEP with antidepressants, although the risk of type 2 diabetes increased compared to HCs in a crude analysis, it decreased when comorbidity was adjusted for. In the group of DEP without antidepressants, the risk of type 2 diabetes decreased both in the crude model and the adjusted models. The risk varied by age group and classes or ingredients of antidepressants, with young adult patients showing an increased risk even in the fully adjusted model.ConclusionOverall, those with depression had a reduced risk of type 2 diabetes. However, the risk varied according to the age at onset, comorbidity, and type of antidepressants.

Background We explored the association between continuous glucose monitoring (CGM) use and glycemia among adults with type 1 diabetes mellitus (T1DM) and determined the status of CGM metrics among adults with T1DM using CGM in the real-world. Methods For this propensity-matched cross-sectional study, individuals with T1DM who visited the outpatient clinic of the Endocrinology Department of Samsung Medical Center between March 2018 and February 2020 were screened. Among them, 111 CGM users (for ≥9 months) were matched based on propensity score considering age, sex, and diabetes duration in a 1:2 ratio with 203 CGM never-users. The association between CGM use and glycemic measures was explored. In a subpopulation of CGM users who had been using official applications (not “do-it-yourself” software) such that Ambulatory Glucose Profile data for ≥1 month were available (n=87), standardized CGM metrics were summarized. Results Linear regression analyses identified CGM use as a determining factor for log-transformed glycosylated hemoglobin. The fully-adjusted odds ratio (OR) and 95% confidence interval (CI) for uncontrolled glycosylated hemoglobin (>8%) were 0.365 (95% CI, 0.190 to 0.703) in CGM users compared to never-users. The fully-adjusted OR for controlled glycosylated hemoglobin (

Abstract It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65–69, 70–74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P

Background This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated. Methods We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM. Results The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002. Conclusion The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone.

AimWe investigated the association between total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) variability and cancer patient mortality risk.MethodsWe retrospectively analyzed 42,539 cancer patients who were not receiving lipid-lowering agents and who had at least three TC measurements within 2 years of their initial cancer diagnosis. Using a multivariable Cox regression model, the risk of mortality was evaluated.ResultsIn multivariable analysis, Q2 (adjusted hazard ratio [aHR]: 1.32, 95% confidence interval (CI): 1.24–1.41), Q3 (aHR: 1.66, 95% CI: 1.56–1.76), and Q4 (aHR: 1.96, 95% CI: 1.84–2.08) of coefficient of variation (CV) in TC were significantly associated with mortality risk compared to Q1, showing a linear association between higher TC variability and mortality (P for trend

This review explores the factors that improve meat protein digestibility and applies the findings to the development of home meal replacements with improved protein digestion rates in older adults. Various methods improve the digestion rate of proteins, such as heat, ultrasound, high pressure, or pulse electric field. In addition, probiotics aid in protein digestion by improving the function of digestive organs and secreting enzymes. Plant-derived proteases, such as papain, bromelain, ficin, actinidin, or zingibain, can also improve the protein digestion rate; however, the digestion rate is dependent on the plant enzyme used and protein characteristics. Sous vide processing improves the rate and extent of protein digestibility, but the protein digestion rate decreases with increasing temperature and heating time. Ultrasound, high pressure, or pulsed electric field treatments degrade the protein structure and increase the proteolytic enzyme contact area to improve the protein digestion rate.

Abstract Whether metabolic dysfunction-associated fatty liver disease (MAFLD) can replace nonalcoholic fatty liver disease (NAFLD) is under debate. This study evaluated which definition better predicted incident chronic kidney disease (CKD). This was a 5.3-year (range, 2.8–8.3) retrospective cohort study of 21,713 adults who underwent at least two serial health examinations. Cox analyses were used to compare the risk of incident CKD among non-fatty liver disease (FLD) without metabolic dysregulation (MD; reference), non-FLD with MD, MAFLD-only, NAFLD-only, or both-FLD groups. Non-FLD with MD group (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.00–1.53), both-FLD group (HR 1.50, 95% CI 1.19–1.89), and MAFLD-only group (HR 1.97, 95% CI 1.49–2.60), but not NAFLD-only group (HR 1.06, 95% CI 0.63–1.79) demonstrated an increased risk of CKD. The increased risk of CKD was significant in MAFLD subgroups with overweight/obesity (HR 2.94, 95% CI 1.91–4.55), diabetes (HR 2.20, 95% CI 1.67–2.90), MD only (HR 1.50, 95% CI 1.19–1.89), excessive alcohol consumption (HR 2.71, 95% CI 2.11–3.47), and viral hepatitis (HR 2.38, 95% CI 1.48–3.84). The switch from NAFLD to MAFLD criteria may identify a greater number of individuals at CKD risk. The association was also significant in MAFLD patients with excessive alcohol consumption or viral hepatitis.

Continuous glucose monitoring (CGM) technology has evolved over the past decade with the integration of various devices including insulin pumps, connected insulin pens (CIPs), automated insulin delivery (AID) systems, and virtual platforms. CGM has shown consistent benefits in glycemic outcomes in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) treated with insulin. Moreover, the combined effect of CGM and education have been shown to improve glycemic outcomes more than CGM alone. Now a CIP is the expected future technology that does not need to be worn all day like insulin pumps and helps to calculate insulin doses with a built-in bolus calculator. Although only a few clinical trials have assessed the effectiveness of CIPs, they consistently show benefits in glycemic outcomes by reducing missed doses of insulin and improving problematic adherence. AID systems and virtual platforms made it possible to achieve target glycosylated hemoglobin in diabetes while minimizing hypoglycemia, which has always been challenging in T1DM. Now fully automatic AID systems and tools for diabetes decisions based on artificial intelligence are in development. These advances in technology could reduce the burden associated with insulin treatment for diabetes.

A seated saline loading test (SLT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the most accepted confirmatory tests of primary aldosteronism. However, LC-MS/MS is time-consuming and is not widely available in diagnostic laboratories compared to immunoassay. With immunoassay, it is unknown whether SLT in the seated position is more accurate than that of the supine position, and a cutoff value of post-seated SLT plasma aldosterone concentration (PAC) must be established in the Korean population. Ninety-eight patients underwent SLT in both positions, and post-SLT PAC was measured by LC-MS/MS and radioimmunoassay. We confirmed primary aldosteronism if post-seated SLT PAC by LC-MS/MS exceeded 5.8 ng/dL. The area under the receiver operating characteristic curve was greater for seated than supine SLT (0.928 vs. 0.834, P=0.003). The optimal cutoff value of post-seated SLT by radioimmunoassay was 6.6 ng/dL (sensitivity 83.3%, specificity 92.2%).

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a well-known risk factor for cardiovascular (CV) disease (CVD) and mortality. However, whether the progression or regression of NAFLD can increase or decrease the risk of heart failure (HF) and mortality has not been fully evaluated. We investigated the association between changes in hepatic steatosis and the risks of incident HF (iHF), hospitalization for HF (hHF), and mortality including CV- or liver-related mortality. Methods Using a database from the National Health Insurance Service in Korea from January 2009 to December 2012, we analyzed 240,301 individuals who underwent health check-ups at least twice in two years. Hepatic steatosis was assessed using the fatty liver index (FLI), with an FLI ≥ 60 considered to indicate the presence of hepatic steatosis. According to FLI changes, participants were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models. Results Persistent hepatic steatosis increased the risk of iHF, hHF, and mortality including CV- and liver-related mortality compared with the group that never had steatosis (all P

This study was conducted to determine the effect of natural ingredient seasoning on the reduction of heterocyclic amine (HCA) production that may occur when pork belly is cooked at a very high temperature for a long time. Pork belly seasoned with natural ingredients, such as natural spices, blackcurrant, and gochujang, was cooked using the most common cooking methods, such as boiling, pan fry, and barbecue. HCAs in pork belly were extracted through solid-phase extraction and analyzed via high-performance liquid chromatography. For short-term toxicity, a mouse model was used to analyze weight, feed intake, organ weight, and length; hematology and serology analysis were also performed. Results revealed that HCAs formed only when heating was performed at a very high temperature for a long time, not under general cooking conditions. Although the toxicity levels were not dangerous, the method showing the relatively highest toxicity among various cooking methods was barbecue, and the natural material with the highest toxicity reduction effect was blackcurrant. Furthermore, seasoning pork belly with natural materials containing a large amount of antioxidants, such as vitamin C, can reduce the production of toxic substances, such as HCAs, even if pork belly is heated to high temperatures.

This study evaluated the safety and efficacy of tubeless patch pump called EOPatch in patients with well-controlled type 1 diabetes mellitus (T1DM). This 4-week, two-center, open-label, single-arm study enrolled 10 adult patients diagnosed with T1DM with glycosylated hemoglobin less than 7.5%. The co-primary end points were patch pump usage time for one attachment and number of serious adverse events related to the patch pump. The secondary end points were total amount of insulin injected per patch and changes in glycemic parameters including continuous glucose monitoring data compared to those at study entry. The median usage time per patch was 84.00 hours (interquartile range, 64.50 to 92.50). Serious adverse events did not occur during the trial. Four weeks later, time in range 70 to 180 mg/dL was significantly improved (70.71%±17.14 % vs. 82.96%±9.14%, P=0.01). The times spent below range (180 mg/dL) also improved (All P

Abstract We investigated the additive interaction of diabetes mellitus (DM) and chronic kidney disease (CKD) on the risk of mortality in cancer patients and evaluated the impact of diabetic kidney disease (DKD) on mortality in cancer patients with DM. We retrospectively analyzed 101,684 cancer patients. A multivariable Cox regression model was used for assessing mortality risk. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate the additive interactive effect. The adjusted hazard ratio (aHR, 95%CI) for mortality was significant for those with CKD alone (1.53, 1.39–1.68), DM alone (1.25, 1.2–1.3), and both CKD and DM (1.99, 1.84–2.17) compared to non-CKD and non-DM cancer patients. The additive interaction between CKD and DM was significant (RERI 0.22[95%CI = 0.01–0.42], AP 0.11[0.01–0.21], SI 1.28[1.01–1.62]). Among cancer patients with DM, the presence of DKD raised the aHR for mortality (1.55, 95%CI = 1.33–1.81) compared to those without DKD. Coexistence of DM and CKD at the time of cancer diagnosis was significantly associated with an increased risk of mortality, and their interaction exerted an additive interactive effect on mortality. DKD was significantly associated with an increased risk of mortality in cancer patients with DM.

Abstract We explored the association between cholesterol levels and dementia risk according to the presence of diabetes and statin use. In this population-based longitudinal cohort study, the Korean National Health Insurance Service datasets (2002–2017) were used. Among individuals aged ≥ 40 years who underwent health examinations in 2009 (N = 6,883,494), the hazard of dementia was evaluated according to cholesterol levels. During a median 8.33 years, 263,185 dementia cases were detected. In statin non-users with or without diabetes, the hazards of all-cause dementia were highest for those in the lowest quartile or quintile of low-density lipoprotein-cholesterol (LDL-C) level, showing an inverted J-shaped relationship. Among statin users with or without diabetes, an advance in LDL-C group was associated with an increase in hazards of all-cause dementia. In statin users with diabetes, even very low LDL-C level was not associated with an increased risk of all-cause dementia. Although there was a seemingly paradoxical association between low LDL-C level and dementia risk in statin non-users, the trend was not observed in statin users and is not likely to be clinically relevant. Rather, an advance in LDL-C levels was associated with an increase in the hazard of all-cause dementia in statin users, regardless of the presence of diabetes.

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.

AimWe explored the effectiveness of continuous glucose monitoring for 1 year on glycated A1c reduction in adults with type 1 diabetes mellitus.MethodsWe included type 1 diabetes mellitus adults who were either new continuous glucose monitoring users (N = 155) or non-users who were under standard care (N = 384). Glycated A1c was measured at baseline and 3, 6, 9, and 12 months. Individuals with (N = 155) or without continuous glucose monitoring use (N = 310) were matched 1:2 by propensity score. We used the linear mixed models to identify the quantitative reduction in repeated measures of glycated A1c.ResultsThe change in glycated A1c from baseline to 12 months was −0.5% ± 1.0% for the continuous glucose monitoring user group (N = 155, P < 0.001) and −0.01% ± 1.0% for the non-user group (N = 310, P = 0.816), with a significant difference between the two groups (P = 0.003). Changes in glycated A1c were significant at 3, 6, 9, and 12 months compared with those at baseline in patients using continuous glucose monitoring (P < 0.001), and the changes differed significantly between the groups (P < 0.001). A linear mixed model showed an adjusted treatment group difference in mean reduction in glycated A1c of −0.11% (95% confidence interval, −0.16 to −0.06) each three months. In the continuous glucose monitoring user group, those who achieved more than 70% of time in range significantly increased from 3 months (37.4%) to 12 months (48.2%) (P < 0.001).ConclusionIn this longitudinal study of type 1 diabetes mellitus adults, the use of continuous glucose monitoring for 1 year showed a significant reduction in glycated A1c in real-world practice.

Abstract Background Although both type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are associated with increased risk of cardiovascular disease (CVD), evidence is lacking as to whether the presence of NAFLD confers an additional risk of CVD in patients with T2DM. We investigated the associations between hepatic steatosis and/or fibrosis and risk of myocardial infarction (MI), stroke, heart failure (HF), and mortality in patients with new-onset T2DM. Methods Using the Korean National Health Insurance dataset, we included 139,633 patients diagnosed with new-onset T2DM who underwent a national health screening from January 2009 to December 2012. Hepatic steatosis and advanced hepatic fibrosis were determined using cutoff values for fatty liver index (FLI) and BARD score. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models. Results During the median follow-up of 7.7 years, there were 3,079 (2.2%) cases of MI, 4,238 (3.0%) cases of ischemic stroke, 4,303 (3.1%) cases of HF, and 8,465 (6.1%) all-cause deaths. Hepatic steatosis defined as FLI ≥ 60 was associated with increased risk for MI (HR [95% CI], 1.28 [1.14–1.44]), stroke (1.41 [1.25–1.56]), HF (1.17 [1.07–1.26]), and mortality (1.41 [1.32–1.51]) after adjusting for well-known risk factors. Compared to the group without steatosis, the group with steatosis and without fibrosis (BARD

Background Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Background Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population. Methods This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram. Results Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents. Conclusion The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

ABSTRACT Aims/Introduction Several cross‐sectional studies have shown that delayed heart rate recovery (HRR) after exercise is associated with the development of metabolic syndrome (MetS). However, there has been a lack of comprehensively designed longitudinal studies. Therefore, our aim was to evaluate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with incident MetS. Materials and Methods This was a retrospective longitudinal cohort study of participants without MetS, diabetes, or cardiovascular diseases. The HRR was calculated as the peak heart rate minus the resting heart rate after a 1 min rest (HRR1), a 2 min rest (HRR2), and a 3 min rest (HRR3). Multivariate Cox proportional hazards analysis was performed to investigate the association between HRR and development of MetS. Results There were 676 (31.2%) incident cases of MetS identified during the follow‐up period (9,683 person‐years). The only statistically significant relationship was between HRR3 and the development of MetS. The hazard ratios (HRs) (95% confidence interval [CI]) of incident MetS comparing the first and second tertiles to the third tertile of HRR3 were 1.492 (1.146–1.943) and 1.277 (1.004–1.624) with P = 0.003 after adjustment for multiple risk factors. As a continuous variable, the HR (95% CI) of incident MetS associated with each one‐beat decrease in HRR3 was 1.015 (1.005–1.026) with P = 0.004 after full adjustments. An HRR3 value ≤45 beats per minute (bpm) was associated with a higher risk of incident MetS compared with values >45 bpm, with an HR (95% CI) of 1.304 (1.061–1.602) and P = 0.001. Conclusions The slow phase of HRR, particularly HRR3, might be more sensitive at predicting the risk of MetS.

Few studies have been conducted among Asian children and adolescents with type 1 diabetes mellitus (T1DM) using do-it-yourself artificial pancreas system (DIY-APS). We evaluated real-world data of pediatric T1DM patients using DIY-APS. Data were obtained for 10 patients using a DIY-APS with algorithms. We collected sensor glucose and insulin delivery data from each participant for a period of 4 weeks. Average glycosylated hemoglobin was 6.2%±0.3%. The mean percentage of time that glucose level remained in the target range of 70 to 180 mg/dL was 82.4%±7.8%. Other parameters including time above range, time below range and mean glucose were also within the recommended level, similar to previous commercial and DIY-APS studies. However, despite meeting the target range, unadjusted gaps were still observed between the median basal setting and temporary basal insulin, which should be handled by healthcare providers.

Background To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients. Methods This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability. Results After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6). Conclusion Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

It is unclear whether extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have a direct protective effect on pancreatic islets. In addition, whether culturing MSCs in three dimensions (3D) instead of a monolayer (2D) can induce changes in the cargo of EVs that facilitate the polarization of macrophages into an M2 phenotype has not been investigated. We sought to determine whether EVs from MSCs cultured in 3D can prevent inflammation and dedifferentiation in pancreatic islets and, if so, whether the protective effect is superior to that of EVs from 2D MSCs. Human umbilical cord blood- (hUCB-) MSCs cultured in 3D were optimized according to cell density, exposure to hypoxia, and cytokine treatment based on the ability of the hUCB-MSC-derived EVs to induce the M2 polarization of macrophages. Islets isolated from human islet amyloid polypeptide (hIAPP) heterozygote transgenic mice were cultured in serum-deprived conditions with hUCB-MSC-derived EVs. EVs derived from 3D hUCB-MSCs had more abundant microRNAs involved in M2 polarization of macrophages and had an enhanced M2 polarization ability on macrophages, which was optimized when the 3D culture condition was 2.5×104 cells per spheroid without preconditioning with hypoxia and cytokine exposure. When islets isolated from hIAPP heterozygote transgenic mice were cultured in serum-deprived conditions with hUCB-MSC-derived EVs, the EVs derived from 3D hUCB-MSCs suppressed the expression of proinflammatory cytokines and caspase-1 in pancreatic islets and increased the proportion of M2-polarized islet-resident macrophages. They improved glucose-stimulated insulin secretion, reduced the expression of Oct4 and NGN3, and induced the expression of Pdx1 and FoxO1. The greater suppression of IL-1β, NLRP3 inflammasome, caspase-1, and Oct4 and induction of Pdx1 and FoxO1 were found in islets cultured with the EVs derived from 3D hUCB-MSCs. In conclusion, EVs derived from 3D hUCB-MSCs optimized for M2 polarization attenuated nonspecific inflammation and preserved β-cell identity of pancreatic islets.

Objective: The endocrine pancreatic β-cells play a pivotal role in maintaining whole-body glucose homeostasis and its dysregulation is a consistent feature in all forms of diabetes. However, knowledge of intracellular regulators that modulate β-cell function remains incomplete. We investigated the physiological role of ROCK1 in the regulation of insulin secretion and glucose homeostasis. Methods: Mice lacking ROCK1 in pancreatic β-cells (RIP-Cre; ROCK1loxP/loxP, β-ROCK1−/−) were studied. Glucose and insulin tolerance tests as well as glucose-stimulated insulin secretion (GSIS) were measured. An insulin secretion response to a direct glucose or pyruvate or pyruvate kinase (PK) activator stimulation in isolated islets from β-ROCK1−/− mice or β-cell lines with knockdown of ROCK1 was also evaluated. A proximity ligation assay was performed to determine the physical interactions between PK and ROCK1. Results: Mice with a deficiency of ROCK1 in pancreatic β-cells exhibited significantly increased blood glucose levels and reduced serum insulin without changes in body weight. Interestingly, β-ROCK1−/− mice displayed a progressive impairment of glucose tolerance while maintaining insulin sensitivity mostly due to impaired GSIS. Consistently, GSIS markedly decreased in ROCK1-deficient islets and ROCK1 knockdown INS-1 cells. Concurrently, ROCK1 blockade led to a significant decrease in intracellular calcium and ATP levels and oxygen consumption rates in isolated islets and INS-1 cells. Treatment of ROCK1-deficient islets or ROCK1 knockdown β-cells either with pyruvate or a PK activator rescued the impaired GSIS. Mechanistically, we observed that glucose stimulation in β-cells greatly enhanced ROCK1 binding to PK. Conclusions: Our findings demonstrate that β-cell ROCK1 is essential for glucose-stimulated insulin secretion and for glucose homeostasis and that ROCK1 acts as an upstream regulator of glycolytic pyruvate kinase signaling.

GV1001, a human telomerase reverse transcriptase catalytic subunit-derived 16-mer peptide, has been developed as a novel anticancer vaccine against various cancers including pancreatic cancer. In the current study, we demonstrate the regulatory roles and mechanisms of GV1001 in endothelial cell responses in vitro and microvessel sprouting ex vivo. GV1001 markedly inhibits vascular endothelial growth factor-A (VEGF-A)-stimulated endothelial cell permeability, proliferation, migration, invasion, tube formation as well as microvessel outgrowth from rat aortic rings. These anti-angiogenic effects of GV1001 were associated with the inhibition of VEGF-A/VEGFR-2 signaling pathways, redistribution of vascular endothelial-cadherin to cell–cell contacts, and down-regulation of VEGFR-2 and matrix metalloproteinase-2. Furthermore, GV1001 suppresses the proliferation and invasion of non-small cell lung cancer cells, and the release of VEGF from the cells, suggesting the regulatory role of GV1001 in tumor-derived angiogenesis as well as cancer cell growth and progression. Collectively, our study reports the pharmacological potential of GV1001 in the regulation of angiogenesis, and warrants further evaluation and development of GV1001 as a promising therapeutic agent for a variety of angiogenesis-related diseases including cancer.

Purpose: The purpose of this study was to investigate the effect of aging on bladder function and caveolin protein expression in rat urothelium. Materials and Methods: Female Sprague-Dawley rats were divided into the following two groups: young age control group (12 weeks) and old-aged group of rats (80 weeks). Urodynamic measurements were taken to compare the contraction interval and the contraction pressure between the two groups. The expression and cellular localization of caveolin 1 and 2 in the urothelium of the rat urinary bladder were determined by Western blot and immunofluorescence microscopy. Results: In cystometrograms, the contraction interval (min) was significantly shorter in the old-aged group (3.7±0.5 min) than in the young age control group (6.2±0.8 min). Also, the average contraction pressure (mmHg) was lower in the old-aged group (8.4±0.6 mmHg) than in the young age control group (13.2±1.3 mmHg). Caveolin 1 and 2 were expressed in the subepithelial area in the urothelium. The protein expression of both caveolin 1 and 2 was significantly lower in the old-aged group than in the young age control group. Conclusions: Aging caused a significant change in the expression of caveolin 1 and 2 in the urothelium of the rat urinary bladder. These findings suggest that these molecules might have specific roles in the functional change of the urinary bladder that occurs in association with aging.

Abstract Aims/Introduction We estimated the hazards of cardiovascular diseases (CVDs) and early all‐cause mortality in Korean adults according to the presence of recently diagnosed type 2 diabetes (type 2 diabetes for

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. Methods We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. Results A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI

We report the development of a gamma-ray imaging device, named Large-Area Hybrid Gamma Imager (LAHGI), featuring high imaging sensitivity and good imaging resolution over a broad energy range. A hybrid collimation method, which combines mechanical and electronic collimation, is employed for a stable imaging performance based on large-area scintillation detectors for high imaging sensitivity. The system comprises two monolithic position-sensitive NaI(Tl) scintillation detectors with a crystal area of 27 × 27 cm2 and a tungsten coded aperture mask with a modified uniformly redundant array (MURA) pattern. The performance of the system was evaluated under several source conditions. The system showed good imaging resolution (i.e., 6.0–8.9° FWHM) for the entire energy range of 59.5–1330 keV considered in the present study. It also showed very high imaging sensitivity, successfully imaging a 253 μCi 137Cs source located 15 m away in 1 min; this performance is notable considering that the dose rate at the front surface of the system, due to the existence of the 137Cs source, was only 0.003 μSv/h, which corresponds to ∼3% of the background level.

Background Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. Conclusion CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Abstract Aims/Introduction We aimed to determine whether mean and visit‐to‐visit glycated hemoglobin (HbA1c) variability independently increase the incidence of non‐alcoholic fatty liver disease (NAFLD) across the diabetic continuum from normal glucose tolerance (NGT) to established diabetes. Materials and Methods In a longitudinal cohort study, 21,123 participants underwent five or more annual health screening checkups. Participants were categorized into diabetes (n = 1,635), prediabetes (n = 6,650) and NGT (n = 12,838) groups. Mean, standard deviation (SD) and coefficient of variation data on HbA1c were obtained from three consecutive measurements. The associations between those data and incident NAFLD were analyzed using Cox regressions. Results Over a median follow‐up period of 57 months, 3,860 (18.3%) participants developed NAFLD. The risk of NAFLD increased continuously, with the mean HbA1c beginning at 4.9%, even in the NGT group. We found a significant association between increasing HbA1c variability and incident NAFLD (coefficient of variation, adjusted hazard ratio 1.14, 95% confidence interval 1.01–1.29; standard deviation, adjusted hazard ratio 1.19, 95% confidence interval 1.05–1.36) in the diabetes group, but not in the NGT or prediabetes group. Consistent findings were observed when NAFLD patients with a low possibility of fibrosis were excluded. The association between the coefficient of variation of HbA1c and incident NAFLD in the diabetes group was significant only in those with an increasing trend of post‐baseline HbA1c (adjusted hazard ratio 1.24, 95% confidence interval 1.01–1.52). Conclusions Increased mean HbA1c levels elevated the risk of incident NAFLD, even with NGT. Increases in visit‐to‐visit variability of HbA1c independently elevated the risk of incident NAFLD, but only in the diabetes group.

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.