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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.

Abstract Background Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation. Results The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed. Conclusions This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28–60 is due to the turnover time of AMs, estimated around 1–2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.

Abstract The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P

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.

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

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 Background Nanodiamonds (NDs) have gained a rapidly growing interest in biomedical applications; however, little is known regarding their biokinetics owing to difficulties in measurements and limited synthesis/purification technologies. In this study, we investigated the distribution kinetics of detonation-synthesized NDs in mice via intravenous injection to evaluate the parameters that determine the behavior of the particles. We prepared two distinctive NDs that controlled the sp 3 /sp 2 carbon ratio and particle size by coating them with serum proteins. The four control samples were intravenously injected into mice, and tissue distribution and clearance were evaluated at 30 min and 1, 7, and 28 days post-injection. Results The sp 3 /sp 2 carbon ratio showed no correlation with the organ distribution of the NDs. However, hydrodynamic size showed an excellent correlation with organ distribution levels: a negative correlation in the liver and positive correlations in the spleen and lungs. Furthermore, the deposition levels of NDs in the lung suggest that particles smaller than 300 nm could avoid lung deposition. Finally, a similar organ distribution pattern was observed in mice injected with carbon black nanoparticles controlled hydrodynamic size. Conclusions In conclusion, the tissue distribution of NDs is modulated not by the sp 3 /sp 2 carbon ratio but by the hydrodynamic size, which can provide helpful information for targeting the tissue of NDs. Furthermore, the organ distribution pattern of the NDs may not be specific to NDs but also can apply to other nanoparticles, such as carbon black.

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.

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 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

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.

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 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.

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.

Introduction: The receptor for advanced glycation end products (RAGE) and its ligands, such as high-mobility group protein box 1 (HMGB1), play an important role in the accumulation of extracellular matrix in chronic kidney diseases with tubulointerstitial fibrosis. Blocking RAGE signaling with soluble RAGE (sRAGE) is a therapeutic candidate for renal fibrosis.Methods: NRK-52E cells were stimulated with or without HMGB1 and incubated with sRAGE in vitro. Sprague-Dawley rats were intraperitoneally treated with sRAGE after unilateral ureteral obstruction (UUO) operation in vivo.Results: HMBG1-stimulated NRK-52E cells showed increased fibronectin expression, type I collagen, α-smooth muscle actin, and connective tissue growth factor, which were attenuated by sRAGE. The mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of nuclear factor kappa B (NF-κB) were enhanced in NRK-52E cells exposed to HMBG1, and sRAGE treatment alleviated the activation of the MAPK and NF-κB pathways. In the UUO rat models, sRAGE significantly ameliorated the increased renal fibronectin, type I collagen, and α-smooth muscle actin expressions. Masson’s trichrome staining confirmed the anti-fibrotic effect of sRAGE in the UUO rat model. RAGE also significantly attenuated the activation of the MAPK pathway and NF-κB, as well as the increased number of infiltrated macrophages within the tubulointerstitium in the kidney of the UUO rat models.Conclusion: These findings suggest that RAGE plays a pivotal role in the pathogenesis of renal fibrosis and that its inhibition by sRAGE may be a potential therapeutic approach for renal fibrosis.

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 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 The NLRP3 inflammasome is activated by mitochondrial damage and contributes to kidney fibrosis. However, it is unknown whether PGC-1α, a key mitochondrial biogenesis regulator, modulates NLRP3 inflammasome in kidney injury. Primary renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-β1 with or without Ppargc1a plasmid, PGC-1α activator (metformin), and siPGC-1α. In vivo, adenine-fed and unilateral ureteral obstruction (UUO) mice were treated with metformin. In vitro, TGF-β1 treatment to RTECs suppressed the expressions of PGC-1α and mitochondrial dynamic-related genes. The NLRP3 inflammasome was also activated and the expression of fibrotic and cell injury markers was increased. PGC-1α induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury. The opposite changes were observed by siPGC-1α. The oxidative stress levels, which are inducers of the NLRP3 inflammasome, were increased and the expression of TNFAIP3, a negative regulator of NLRP3 inflammasome regulated by PGC-1α, was decreased by TGF-β1 and siPGC-1α. However, PGC-1α restoration reversed these alterations. In vivo, adenine-fed and UUO mice models showed suppression of PGC-1α and TNFAIP3 and dysregulated mitochondrial dynamics. Moreover, the activation of oxidative stress and NLRP3 inflammasome, and kidney fibrosis were increased in these mice. However, these changes were significantly reversed by metformin. This study demonstrated that kidney injury was ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome via modulation of mitochondrial viability and dynamics.

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.

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.

Objectives Tetracycline (TC) antibiotics have a risk of causing gastrointestinal and hepatic disorders and, in rare cases, photosensitivity and deposition in bone tissue. Methods Therefore, it is urgent to develop a technology that can completely remove TC remaining in the water. In this study, a new type of sonophotocatalytic decomposition system that can efficiently decompose TC, a water-based recalcitrant trace pollutant, was proposed. Results and Discussion As a sonophotocatalyst, xCeO2-(1-x)ZrO2 (x = 0, 0.25, 0.5, 0.75, and 1) binary nanocomposites were synthesized by hydrothermal methods, followed by X-ray diffraction, Fourier-transform infrared spectroscopy, field emission scanning electron microscope, UV-Vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller surface area techniques. Interestingly, the 0.75CeO2-0.25ZrO2 (CZ0.75) nanocomposite had low adsorption and removal ability of TC in the absence of light, but due to the synergistic effect of the material and the advanced treatment system, the remaining TC was removed by 89.2% under sonophoto irradiation for 60 min. For CZ0.75, the effect of operating factors such as initial pH of solution, catalyst dosage, reaction time, initial TC concentration, and ultrasonic intensity was studied and the mechanism was analyzed. Conclusion In addition, through LC-MS analysis, intermediate products obtained in the TC degradation process using the CZ0.75 catalyst and the TC degradation pathway were identified.

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

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.

Background Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. Methods This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. Results Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. Conclusion Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

Background Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. Methods This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. Results The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. Conclusion This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

In this study, we developed two novel conjugated polymers that can easily be doped with F4TCNQ organic dopants using a sequential doping method and then studied their organic thermoelectric (OTE) properties. In particular, to promote the intermolecular ordering of OTE polymers in the presence of the F4TCNQ dopant, alkylthiazole-based conjugated building blocks with highly planar backbone structures were synthesized and copolymerized. All polymers showed strong molecular ordering and edge-on orientation in the film state, even in the presence of the F4TCNQ organic dopant. Thus, the sequential doping process barely changed the molecular ordering of the polymer films while making efficient molecular doping. In addition, the doping efficiency was improved in the more π-extended polymer backbones with thienothiophene units due to the emptier space in the polymer lamellar structure to locate ionized F4TCNQ. Moreover, the study of organic thin-film transistors (OTFTs) revealed that higher hole mobility in OTFTs was the key to increasing the electrical conductivity of OTE devices fabricated using the sequential doping method.

Abstract Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system Xc − (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.

Objectives:Adsorption characteristics in aqueous solution were investigated to effectively remove heavy metals by the crystallization of FeS and reaction kinetics were analyzed to compare with heavy metal adsorption characteristics of zeolite. Methods:The adsorption characteristics of each media were analyzed using Langmuir adsorption isotherm, and the adsorption reaction kinetics of heavy metals (Pb, Cu, Zn) on zeolite and FeS media were analyzed by a pseudo-first or pseudo-second order reaction kinetics. Results and Discussion:The maximum adsorption capacity of zeolite was highest in Pb, and the adsorption preference was in the order of Pb>Cu>Zn. In the case of FeS media, Cu was found to have a higher adsorption capacity than Pb or Zn, and the adsorption preference was observed to be Cu>Pb>Zn. It was found that the adsorption mechanism is based on chemical adsorption (chemisorption) because adsorption of each heavy metal onto zeolite or FeS media is more suitable for pseudo-second order kinetics. Conclusions:It was found that the removal of heavy metals through FeS media has a different pattern from zeolite, and when comparing the adsorption capacity of each media, it was found that FeS media is more effective for Zn or Cu except Pb.

Abstract Background Despite the numerous healthcare smartphone applications for self-management of diabetes, patients often fail to use these applications consistently due to various limitations, including difficulty in inputting dietary information by text search and inconvenient and non-persistent self-glucose measurement by home glucometer. We plan to apply a digital integrated healthcare platform using an artificial intelligence (AI)-based dietary management solution and a continuous glucose monitoring system (CGMS) to overcome those limitations. Furthermore, medical staff will be performing monitoring and intervention to encourage continuous use of the program. The aim of this trial is to examine the efficacy of the program in patients with type 2 diabetes mellitus (T2DM) who have HbA1c 53–69 mmol/mol (7.0–8.5%) and body mass index (BMI) ≥ 23 mg/m2. Methods This is a 48-week, open-label, randomized, multicenter trial consisting of patients with type 2 diabetes. The patients will be randomly assigned to three groups: control group A will receive routine diabetes care; experimental group B will use the digital integrated healthcare platform by themselves without feedback; and experimental group C will use the digital integrated healthcare platform with continuous glucose monitoring and feedback from medical staff. There are five follow-up measures: baseline and post-intervention at weeks 12, 24, 36, and 48. The primary end point is change in HbA1c from baseline to six months after the intervention. Discussion This trial will verify the effectiveness of a digital integrated healthcare platform with an AI-driven dietary solution and a real-time CGMS in patients with T2DM. Trial registration Clinicaltrials.gov NCT 04161170, registered on 08 November 2019. https://clinicaltrials.gov/ct2/show/NCT04161170?term=NCT04161170&draw=2&rank=1

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

BackgroundImpaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.MethodsWe analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.ResultsLV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).ConclusionsLiver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.

Background and aims: Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side. Methods: Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side. Results: Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or 7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity. Conclusion: In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.

BackgroundSerum albumin and uric acid have been positively linked to metabolic syndrome (MetS). However, the association of MetS incidence with the combination of uric acid and albumin levels has not been investigated. We explored the association of albumin and uric acid with the risk of incident MetS in populations divided according to the levels of these two parameters.MethodsIn this retrospective longitudinal study, 11,613 non-MetS participants were enrolled among 24,185 individuals who had undergone at least four annual check-ups between 2006 and 2012. The risk of incident MetS was analyzed according to four groups categorized by the sex-specific medians of serum albumin and uric acid.ResultsDuring 55,407 person-years of follow-up, 2,439 cases of MetS developed. The risk of incident MetS increased as the uric acid category advanced in individuals with lower or higher serum albumin categories with hazard ratios (HRs) of 1.386 (95% confidence interval [CI], 1.236 to 1.554) or 1.314 (95% CI, 1.167 to 1.480). However, the incidence of MetS increased with higher albumin levels only in participants in the lower uric acid category with a HR of 1.143 (95% CI, 1.010 to 1.294).ConclusionHigher levels of albumin were associated with an increased risk of incident MetS only in individuals with lower uric acid whereas higher levels of uric acid were positively linked to risk of incident MetS regardless of albumin level.

BackgroundThe prevalence and incidence of type 1 diabetes mellitus (T1DM) in all age groups and the prevalence of metabolic syndrome in patients with T1DM in Korea were estimated.MethodsThe incidence and prevalence of T1DM between 2007 and 2013 were calculated using the Korean National Health Insurance Service (NHIS) datasets of claims. Clinical characteristics and prevalence of metabolic syndrome in individuals with T1DM between 2009 and 2013 were determined using the database of NHIS preventive health checkups.ResultsThe prevalence of T1DM in Korea between 2007 and 2013 was 0.041% to 0.047%. The annual incidence rate of T1DM in Korea in 2007 to 2013 was 2.73 to 5.02/100,000 people. Although the incidence rate of typical T1DM was highest in teenagers, it remained steady in adults over 30 years of age. In contrast, the incidence rate of atypical T1DM in 2013 was higher in people aged 40 years or older than in younger age groups. Age- and sex-adjusted prevalence of metabolic syndrome in patients with T1DM was 51.65% to 55.06% between 2009 and 2013.ConclusionT1DM may be more common in Korean adults than previously believed. Metabolic syndrome may be a frequent finding in individuals with T1DM in Korea.

Abstract Background Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. Methods A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. Results During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54–0.68). Furthermore, compared with SMI changes 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. Conclusions An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

Abstract Background We investigated whether glycated albumin (GA) and its variability are associated with cardiovascular autonomic neuropathy (CAN) and further compared their associations with glycated hemoglobin (HbA1c). Methods This retrospective longitudinal study included 498 type 2 diabetic patients without CAN. CAN was defined as at least two abnormal results in parasympathetic tests or presence of orthostatic hypotension. The mean, standard deviation (SD), and coefficient of variance (CV) were calculated from consecutively measured GA (median 7 times) and HbA1c levels (median 8 times) over 2 years. Logistic regression analysis was used to compare the associations between CAN and GA- or HbA1c-related parameters. Receiver operating characteristic (ROC) curve analysis was used to compare the predictive power for CAN between GA- and HbA1c-related parameters. Results A total of 53 subjects (10.6%) developed CAN over 2 years. The mean, SD, and CV of GA or HbA1c were significantly higher in subjects with CAN. Higher mean GA and GA variability were associated with the risk of developing CAN, independent of conventional risk factors and HbA1c. In ROC curve analysis, the SD and CV of GA showed higher predictive value for CAN compared to the SD and CV of HbA1c, whereas the predictive value of mean GA did not differ from that of mean HbA1c. The mean, SD, and CV of GA showed additive predictive power to detect CAN development along with mean HbA1c. Conclusions Higher serum GA and its variability are significantly associated with the risk of developing CAN. Serum GA might be a useful indicator for diabetic complications and can enhance HbA1c’s modest clinical prediction for CAN.

Abstract Background A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. Methods This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. Discussion This clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field. Trial registration Clinicaltrials.gov NCT 03112343 . Registered on 12 April 2017.

BackgroundAlthough the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. We aimed to investigate whether, and which, statins affected renal function in Asian patients with diabetes.MethodsWe enrolled 484 patients with diabetes who received statin treatment for more than 12 months. We included patients treated with moderate-intensity dose statin treatment (atorvastatin 10 to 20 mg/day or rosuvastatin 5 to 10 mg/day). The primary outcome was a change in estimated glomerular filtration rate (eGFR) during the 12-month statin treatment, and rapid renal decline was defined as a >3% reduction in eGFR in a 1-year period.ResultsIn both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs (from 80.3 to 78.8 mL/min/1.73 m2 for atorvastatin [P=0.012], from 79.1 to 76.1 mL/min/1.73 m2 for rosuvastatin [P=0.001]). A more rapid eGFR decline was observed in the rosuvastatin group than in the atorvastatin group (48.7% vs. 38.6%, P=0.029). Multiple logistic regression analyses demonstrated more rapid renal function loss in the rosuvastatin group than in the atorvastatin group after adjustment for other confounding factors (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.42).ConclusionThese results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin.