The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

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 < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 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.

Combination of low- or moderate-intensity statin and ezetimibe versus high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: A propensity-matched nationwide cohort study.

AIMS: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting. METHODS AND RESULTS: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first.Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.77-0.92, P < 0.001) as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups. CONCLUSIONS: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.

We compared the preventive effect of low- or moderate-statin with ezetimibe combination and high-intensity statin monotherapy on cardiovascular disease and all-cause death.Low- or moderate-intensity statin with ezetimibe is beneficial for reducing a composite of MI, stroke, and all-cause death.Moderate-intensity statin with ezetimibe reduced 19% of MI and 22% of stroke, compared with high-intensity statin.Statin with ezetimibe combination might be attractive bypass for primary prevention, beyond an alternative to high-intensity statin.

Comparison of the Efficacy of Ezetimibe Combination Therapy and High-Intensity Statin Monotherapy in Type 2 Diabetes.

CONTEXT: Low-density lipoprotein cholesterol (LDL-C)-lowering therapy is considerably important in preventing cardiovascular disease (CVD) among patients with diabetes. Studies comparing CVD, stroke, and mortality outcomes of low- or moderate-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy in patients with diabetes remain lacking. OBJECTIVE: This study compared the primary prevention effect of myocardial infarction (MI), stroke, and all-cause death between combination therapy of low- or moderate-intensity statins and ezetimibe and high-intensity statin monotherapy in patients with diabetes using the Korean National Health Insurance claims database. METHODS: Patients aged ≥20 years with type 2 diabetes and dyslipidemia were enrolled. The combination therapy of low- or moderate-intensity statin and ezetimibe was compared with high-intensity statin monotherapy after a propensity score-matched analysis. The incidence of composite outcomes consisting of MI, stroke, and all-cause death and each component were analyzed. RESULTS: In moderate-intensity statin therapy with ezetimibe combination therapy, LDL-C (74 ± 37.9 mg/dL vs 80.8 ± 38.8 mg/dL, P < .001) and the incidence of composite outcomes were lower (hazard ratio 0.85, 95% CI 0.74-0.98) than those in high-intensity statin monotherapy. Meanwhile, no significant difference was observed in the LDL-C levels and composite outcomes between low-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy. CONCLUSION: Adding ezetimibe to a moderate-intensity statin in patients with type 2 diabetes has a greater LDL-C-lowering effect and greater primary prevention of composite outcomes than that of high-intensity statin monotherapy.

Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study.

BACKGRUOUND: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD. METHODS: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study. RESULTS: Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users. CONCLUSION: The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes in patients with type 2 diabetes mellitus undergoing anthracycline-containing chemotherapy: an emulated target trial using nationwide cohort data in South Korea.

Novel hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. This study aimed to evaluate whether SGLT2i improve the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) undergoing AC-containing chemotherapy. A total of 81,572 patients who underwent AC chemotherapy between 2014 and 2021 were recruited from a nationwide Korean cohort. Patients were classified into three groups: patients with T2DM taking SGLT2i (n = 780) and other hypoglycemic agents excluding SGLT2i (non-SGLT2i; n = 3,455) during AC chemotherapy, and the non-DM group (n = 77,337). The clinical outcome was a composite of heart failure hospitalization, acute myocardial infarction, ischemic stroke, and death. After propensity score matching, 779 SGLT2i users were compared with 7800 non-DM patients and 2,337 non-SGLT2i users. The SGLT2i group had better composite outcomes compared with the non-DM group (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [95% CI] = 0.25-0.51) and compared with the non-SGLT2i group (adjusted HR = 0.47, 95% CI = 0.32-0.69). In conclusion, SGLT2i may contribute to improving clinical outcomes in patients with T2DM undergoing AC-containing chemotherapy, through an emulated target trial using Korean nationwide cohort data.

Peroxisome proliferator-activated receptor γ activation ameliorates liver fibrosis-differential action of transcription factor EB and autophagy on hepatocytes and stellate cells.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) activation suppresses HSC activation and liver fibrosis. Moreover, autophagy is implicated in hepatic lipid metabolism. Here, we determined whether PPARγ activation ameliorates HSC activation by downregulating transcription factor EB (TFEB)-mediated autophagy. METHODS AND RESULTS: Atg7 or Tfeb knockdown in human HSC line LX-2 cells downregulated the expression of fibrogenic markers including α smooth muscle actin, glial fibrillary acidic protein, and collagen type 1. Conversely, Atg7 or Tfeb overexpression upregulated fibrogenic marker expression. Rosiglitazone (RGZ)-mediated PPARγ activation and/or overexpression in LX-2 cells and primary HSCs decreased autophagy, as indicated by LC3B conversion, total and nuclear-TFEB contents, mRFP-LC3 and BODIPY 493/503 colocalization, and GFP-LC3 and LysoTracker colocalization. RGZ treatment decreased liver fat content, liver enzyme levels, and fibrogenic marker expression in high-fat high-cholesterol diet-fed mice. Electron microscopy showed that RGZ treatment restored the high-fat high-cholesterol diet-mediated lipid droplet decrease and autophagic vesicle induction in primary HSCs and liver tissues. However, TFEB overexpression in LX-2 cells offset the aforementioned effects of RGZ on autophagic flux, lipid droplets, and fibrogenic marker expression. CONCLUSIONS: Activation of PPARγ with RGZ ameliorated liver fibrosis and downregulation of TFEB and autophagy in HSCs may be important for the antifibrotic effects of PPARγ activation.

Subtypes of type 2 diabetes and their association with outcomes in Korean adults - A cluster analysis of community-based prospective cohort.

BACKGROUND: Little is known about the subtypes of type 2 diabetes (T2D) and their association with clinical outcomes in Asians. METHODS: We performed data-driven cluster analysis in patients with newly diagnosed drug-naive T2D (n = 756) from the Korean Genome and Epidemiology Study. Clusters were based on five variables (age at diagnosis, BMI, HbA1c, and HOMA2 ß-cell function, and insulin resistance). RESULTS: We identified four clusters of patients with T2D according to k-means clustering: cluster 1 (22.4 %, severe insulin-resistant diabetes [SIRD]), cluster 2 (32.7 %, mild age-related diabetes [MARD]), cluster 3 (32.7 %, mild obesity-related diabetes [MOD]), and cluster 4 (12.3 %, severe insulin-deficient diabetes [SIDD]). During 14 years of follow-up, individuals in the SIDD cluster had the highest risk of initiation of glucose-lowering therapy compared to individuals in the other three clusters. Individuals in the MARD and SIDD clusters showed the highest risk of chronic kidney disease and cardiovascular disease, and individuals in the MOD clusters showed the lowest risk after adjusting for other risk factors (P < 0.05). CONCLUSIONS: Patients with T2D can be categorized into four subgroups with different glycemic deterioration and risks of diabetes complications. Individualized management might be helpful for better clinical outcomes in Asian patients with different T2D subgroups.

An Integrated Digital Health Care Platform for Diabetes Management With AI-Based Dietary Management: 48-Week Results From a Randomized Controlled Trial.

OBJECTIVE: We investigated the efficacy of an integrated digital health care platform with artificial intelligence (AI)-based dietary management in adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: In this 48-week, open-label, randomized, multicenter clinical trial, overweight or obese adults with T2D were randomly assigned to one of three groups in a 1:1:1 ratio: group A received routine diabetes care; group B used the digital integrated health care platform by themselves; and group C used the platform with feedback from medical staff and intermittently applied personal continuous glucose monitoring. The primary end point was the difference of change in HbA1c from baseline to 24 weeks between groups A and B, while secondary end points included changes in HbA1c from baseline to 48 weeks and changes in body weight during follow-up. RESULTS: A total of 294 participants were randomly assigned to group A (n = 99), B (n = 97), or C (n = 98). The decreases in HbA1c from baseline to 24 and 48 weeks in group B (-0.32 ± 0.58% to 24 weeks and -0.28 ± 0.56% to 48 weeks) and group C (-0.49 ± 0.57% to 24 weeks and -0.44 ± 0.62% to 48 weeks) were significantly larger than those in group A (-0.06 ± 0.61% to 24 weeks and 0.07 ± 0.78% to 48 weeks). Groups B and C exhibited greater weight loss than group A from baseline to 24 weeks, and group C demonstrated more weight loss than group A from baseline to week 48. CONCLUSIONS: Among adults with T2D, use of an integrated digital health care platform with AI-driven dietary management resulted in better glycemia and more weight loss.

Low Skeletal Muscle Mass Accompanied by Abdominal Obesity Additively Increases the Risk of Incident Type 2 Diabetes.

CONTEXT: Low skeletal muscle mass often accompanies abdominal obesity in the aging process. OBJECTIVE: We aimed to investigate the effect of reduced skeletal muscle mass and its interaction with abdominal obesity on incident type 2 diabetes. METHODS: This retrospective longitudinal study included 36 304 diabetes-free Koreans who underwent 2 or more health checkups annually or biannually. Appendicular skeletal muscle mass was measured by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI) adjusted for body weight. Presarcopenia was defined as an SMI less than 1 SD of the sex-specific mean for a healthy young reference group. Abdominal obesity was defined using waist circumference greater than or equal to 90 cm for men and greater than or equal to 85 cm for women. Participants were classified into 4 groups of normal, presarcopenia alone, abdominal obesity alone, and presarcopenic obesity according to initial body composition. RESULTS: The cumulative incidence of diabetes was 9.1% during the 7-year follow-up. Compared with the highest tertile, the lowest sex-specific SMI tertile was significantly associated with a greater risk of incident type 2 diabetes (adjusted hazard ratio [HR] = 1.31; 95% CI, 1.18-1.45) in a fully adjusted model. Presarcopenic obesity significantly increased incident diabetes risk (adjusted HR = 1.57; 95% CI, 1.42-1.73) compared with normal body composition, presarcopenia alone, or abdominal obesity alone. CONCLUSION: Low skeletal muscle mass and its coexistence with abdominal obesity additively increased the risk of incident type 2 diabetes independent of the glycometabolic parameters.

Delayed diagnosis of pseudohypoparathyroidism type 1a with rare hypothyroidism since childhood.

Pseudohypoparathyroidism (PHP) is a rare disorder that associates with resistance to parathyroid hormone (PTH). A 21-year old man visited outpatient clinic to treat previously diagnosed hypothyroidism and vitamin D deficiency. Despite daily 150 mcg of levothyroxine supplement, thyroid-stimulating hormone level was elevated, but thyroid autoantibodies were not detected. He showed features of Albright Hereditary Osteodystrophy and elevated serum PTH level with normal albumin-corrected calcium and phosphorus level. The Ellsworth-Howard test proved the blunted response of urinary phosphorus and cyclic adenosine monophosphate after the infusion of the exogenous PTH, suggesting PTH resistance. DNA analysis revealed a heterozygous mutation in the GNAS gene (c.478C > T). Herein, we report a case of PHP type 1a confirmed by clinical, biochemical and molecular analyses. Establishing correct diagnosis of PHP is necessary for efficient therapeutic management.

Trends in the Prevalence of Obesity and Its Phenotypes Based on the Korea National Health and Nutrition Examination Survey from 2007 to 2017 in Korea.

This study used data from the Korea National Health and Nutrition Examination Survey IV-VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (ß=0.326, P trend <0.01) between 2007 and 2017, and especially in men (ß=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (ß=0.565, P trend <0.01), while that of MHO increased only in women (ß=0.179, P<0.05), especially in the younger age group (ß=0.308, P<0.01).

The efficacy and safety of Dendropanax morbifera leaf extract on the metabolic syndrome: a 12-week, placebo controlled, double blind, and randomized controlled trial.

BACKGROUND/OBJECTIVES: The extract from Dendropanax morbifera exhibited diverse therapeutic potentials. We aimed to evaluate the efficacy and safety of D. morbifera leaf extract for improving metabolic parameters in human. SUBJECTS/METHODS: A 12-week, double blind, placebo-controlled and randomized trial included a total of 74 adults, and they were assigned to the placebo group (n = 38) or 700 mg/day of D. morbifera group (n = 36). The efficacy endpoints were changes in glycemic, lipid, obesity, and blood pressure (BP) parameters, in addition to the prevalence of metabolic syndrome (MetS) and the numbers of MetS components. Safety was assessed by monitoring adverse events (AEs). RESULTS: After 12 weeks of treatment, the hemoglobin A1c (HbA1c) level significantly decreased in the D. morbifera group compared to that of the placebo group (difference: -0.13 ± 0.20% vs. 0.00 ± 0.28%, P = 0.031; % of change: -2.27 ± 3.63% vs. 0.10 ± 5.10%, P = 0.025). The homeostatic model assessment for insulin resistance level also decreased significantly from its baseline in the D. morbifera group. The systolic BP of D. morbifera group decreased significantly than that of placebo group (difference: -3.9 ± 9.8 mmHg vs. 3.3 ± 11.7 mmHg, P = 0.005; % of change: -2.8 ± 7.7% vs. 3.3 ± 10.2%, P = 0.005). However, the lipid parameters and body composition including body weight did not differ between the groups. The prevalence of MetS (36.8% vs. 13.9%, P = 0.022) and the incidence of MetS (10.5% vs. 13.9%, P = 0.027) at 12 weeks was significantly lower in the D. morbifera group than it was in the placebo group. No serious AEs occurred in either group. CONCLUSIONS: Supplementation with D. morbifera extracts over a 12-week period improved metabolic parameters such as HbA1c and BP and reduced the prevalence of MetS. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004672.

Effects of Advanced Glycation End Products on Differentiation and Function of Osteoblasts and Osteoclasts.

BACKGROUND: Risk of fragility fractures increases in patients with diabetes mellitus, independent of bone mineral density. In the present study, the effects of advanced glycation end products (AGEs) on differentiation and function of osteoblasts and osteoclasts were investigated. METHODS: AGEs and 25 mM glucose were administered to marrow-derived macrophages and MCT3T3-E1 cells. The effects of AGEs on osteoclast differentiation was investigated using tartrate-resistant acid phosphatase (TRAP) assay. The effects of AGEs on osteoblast differentiation was investigated using alkaline phosphatase (ALP) activity and bone nodule formation assays. Expression of osteoclast-specific and osteoblast-specific genes and effects on cell signaling pathways associated with cell differentiation were analyzed using reverse transcription polymerase chain reaction and western blotting. RESULTS: AGEs significantly decreased TRAP-positive multinucleated cell formation in receptor activator of nuclear factor-κB ligand-induced marrow-derived macrophages in a dose-dependent manner. AGEs suppressed the expression of osteoclast-specific genes, JNK, p38, AKT, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 1 in marrow-derived macrophages. AGEs decreased ALP activity and showed a tendency to decrease bone nodule formation in MC3T3-E1 cells. AGEs suppressed the expression of osteoblast-specific genes, lysyl hydroxylase and lysyl oxidase in MC3T3-E1 cells. CONCLUSION: AGEs suppressed differentiation and function of osteoclasts and osteoblasts, and collagen cross-linking activity. It suggests that AGE may induce bone fragility through low bone turnover and deterioration of bone quality.

Statin use for primary prevention in patients with type 2 diabetes: Can it benefit all ages? - A nationwide propensity-matched cohort study.

AIMS: This study aims to investigate whether statin use is associated with a reduction in CVD and mortality in patients with type 2 diabetes without pre-existing CVD. METHODS: A propensity score-matched cohort analysis using retrospective data was created. Statin users received at least a 90-day prescription, and never used statin before initiation of the study. Statin non-users never received statin throughout the study. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death, and secondary outcome was an individual event. RESULTS: The propensity score matched cohort included 168,045 statin users and 168,045 non-users (mean age 57 years; median follow-up 5.0 years). Compared to statin non-users, the hazard ratio (HR) was 0.72 (95% confidence interval [CI] 0.70-0.73; P < 0.001) for composite outcomes, 0.80 (0.76-0.84; P < 0.001) for MI, 0.74 (0.71-0.76; P < 0.001) for stroke, and 0.68 (0.66-0.70; P < 0.001) for all-cause death in statin users. The risk reduction was most prominent in subjects aged 40-74 years, attenuated but significant in those aged ≥75 years, and not significant in those aged <40 years. CONCLUSIONS: Statin showed a protective effect against CVD and all-cause death in type 2 diabetes; this effect was reduced beyond the age of 75 years and disappeared in young patients aged <40 years.

Low Skeletal Muscle Mass Is Associated With the Presence, Incidence, and Progression of Coronary Artery Calcification.

BACKGROUND: Low skeletal muscle mass (SMM) is an emerging risk factor of cardiovascular disease (CVD). We investigated the association between SMM and coronary artery calcification (CAC). METHODS: We enrolled 19,728 adults free of CVD who underwent computed tomographic estimation of Agatston CAC scores for cross-sectional analysis. Among them, 5,401 subjects who had at least 2 follow-up CAC scores were included in longitudinal analysis. Relative SMM is presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/body weight (kg) × 100]. CAC presence and incidence were defined as CAC score > 0, and CAC progression was defined as √CAC score (follow-up) - √CAC score (baseline) > 2.5. RESULTS: Among all of the subjects (mean age 53.4 years, 80.8% male), the prevalence of CAC was 36.7%. The incidence of CAC was 17.4% during a mean of 3.6 years, and the progression of CAC was 49.9% during a mean of 2.3 years. The lowest SMI quartile was significantly associated with an increased risk of CAC presence (adjusted odds ratio 2.75, 95% confidence interval [CI] 2.45-3.05; P < 0.001), incidence (adjusted hazard ratio [AHR] 1.99, 95% CI 1.36-2.91; P < 0.001), and progression (AHR 1.48, 95% CI 1.25-1.77; P < 0.001) compared with the highest quartile. SMI as a continuous value was also significantly inversely associated with CAC. SMI was the best parameter to be related to CAC among other quantitative indices such as height or body mass index adjusted. CONCLUSIONS: Low SMM is significantly associated with an elevated risk of CAC, independently of other cardiometabolic parameters.

Additive effect of low skeletal muscle mass and abdominal obesity on coronary artery calcification.

OBJECTIVE: We aimed to investigate the interaction of reduced skeletal muscle mass and abdominal obesity on coronary artery calcification (CAC). DESIGN AND METHODS: A total of 19 728 adults free of cardiovascular disease (CVD) who contemporaneously underwent cardiac tomography and bioelectrical impedance analysis were enrolled in a cross-sectional and longitudinal cohort. Skeletal muscle mass index (SMI) was calculated using the following formula: SMI (%) = total appendicular muscle mass (kg)/body weight (kg) × 100 according to sex. CAC presence or incidence was defined as CAC score > 0, and CAC progression was defined as √CAC score (follow-up) - √CAC score (baseline)>2.5. Pre-sarcopenia was defined as SMI ≤ -1.0 s.d. of the sex-specific mean of a young reference group. Abdominal obesity was defined as waist circumference ≥ 90 cm for men and ≥85 cm for women. All individuals were further classified into four groups: normal, abdominal obesity alone, pre-sarcopenia alone, and pre-sarcopenic obesity. RESULTS: Individuals with pre-sarcopenic obesity showed the highest adjusted odds ratio (AOR) for CAC presence (AOR 2.16, 95% CI : 1.98-2.36, P < 0.001) as well as total CAC incidence and progression (adjusted hazard ratio: 1.54, 95% CI: 1.37-1.75, P < 0.001), compared with normal individuals. Pre-sarcopenic obesity significantly increased CAC incidence and progression compared to either pre-sarcopenia or abdominal obesity alone. CONCLUSION: Pre-sarcopenia and abdominal obesity together were significantly associated with a higher CAC presence and increased risk of CAC incidence and progression, independent of traditional CVD risk factors.

Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study.

BACKGROUND: Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes. METHODS: Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit. RESULTS: During the 6-year follow-up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily. CONCLUSION: Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

The Association Between Continuous Glucose Monitoring-Derived Metrics and Cardiovascular Autonomic Neuropathy in Outpatients with Type 2 Diabetes.

Background: Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes complications. This study investigated the associations between CGM-derived TIR, hyperglycemia, and hypoglycemia metrics and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. Methods: A total of 284 patients with type 2 diabetes who underwent CGM using GOLD™ (Medtronic MiniMed) for 3 days or iPro™2 (Medtronic MiniMed) for 6 days and autonomic function tests within 3 months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal result in two or more parasympathetic test, and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests. Results: A total of 84 patients (29.6%) were diagnosed with CAN, and the mean TIR was 57.0% ± 7.0%. A multiple logistic regression analysis revealed that the odds ratio (OR) of presence of CAN was 0.876 [95% confidence interval (CI): 0.79-0.98] per 10% increase in the TIR 70-180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in the TIR was significantly inversely associated with the severity of CAN (OR: 0.89, 95% CI: 0.81-0.98). Among the metrics of hyperglycemia, each 10% increase in a time above range (TAR) >180 mg/dL was also independently correlated with the presence of CAN (OR: 1.141, 97.5% CI: 1.01-1.29) and the severity of CAN (OR: 1.13, 97.5% CI: 1.01-1.26). Conclusion: A TIR 70-180 mg/dL and a TAR >180 mg/dL were significantly associated with CAN in outpatients with type 2 diabetes.

Association of Urinary N-Acetyl-ß-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-ß-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 estimate the 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 (ß=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.

Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling.

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 <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. Scatterplot cutoffs of RIR <0.5 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.