Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Association between cardiovascular disease risk and incident type 2 diabetes mellitus in individuals with prediabetes: A retrospective cohort study.

AIMS: In this study, we aimed to evaluate the impact of overall cardiovascular disease (CVD) risk on the development of incident T2DM in patients with prediabetes. METHODS: We retrospectively enrolled 5,908 subjects with prediabetes who underwent health check-ups at the Asan Medical Center. CVD risk was estimated using the Framingham Risk Score (FRS). We compared moderate- to high-risk groups with low-risk controls based on the FRS. Cox proportional hazards regressions were conducted to estimate the time-to-develop incident T2DM. RESULTS: Among the 5908 subjects with prediabetes, 3031 (51.8 %) were identified to have either moderate or high CVD risk scores. During a median follow-up of 5.2 years, 278 (9.2 %) patients from the moderate- to high-risk group and 171 (5.9 %) from the low-risk group were diagnosed with T2DM. The covariate-adjusted hazard ratio for the incident T2DM was 1.30 (95 % CI, 1.06-1.60, p = 0.011) in the moderate- to high-risk group compared to the low-risk controls. CONCLUSION: Among patients with prediabetes, those with high CVD risk were more likely to develop incident T2DM, as determined by the FRS. CVD risk factors should be properly evaluated and managed in individuals with prediabetes to reduce the risk of both incident T2DM and associated cardiovascular complications.

The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist.

Glucagon-like peptide-1 (GLP-1) receptor agonists have been used extensively in the clinic and have an established safety profile in cardiovascular disease settings. For the treatment of peptide-secreting enteroendocrine cells, most research has focused on developing peptide multi-agonists as most of these cells are multihormonal. Among the various peptides secreted by enteroendocrine cells, the combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) is an attractive strategy for treating type 2 diabetes mellitus (T2DM) because both of these hormones have glucose-lowering actions. Tirzepatide, a synthetic peptide composed of 39 amino acids, functions as a dual receptor agonist of both the GIP and GLP-1 receptors. This unique mechanism of action has earned tirzepatide the nickname "twincretin." Tirzepatide's dual agonist activity may be the mechanism by which tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with T2DM as observed in phase 3 clinical trials. Besides its glucose-lowering and anti-obesity effects, tirzepatide has been reported to have potential cardiovascular benefits. In this review, we discuss the cardiovascular effects of tirzepatide based on the available preclinical and clinical data.

Preserved Muscle Strength Despite Muscle Mass Loss After Bariatric Metabolic Surgery: a Systematic Review and Meta-analysis.

BACKGROUND: Contrary to the previously known concept of muscle mass decrease following bariatric metabolic surgery, changes in muscle strength have been poorly investigated in systematic reviews. In this meta-analysis, we evaluated changes in handgrip strength (HGS) and lean mass (LM) after undergoing bariatric metabolic surgery. METHODS: A systematic literature review using the PubMed, Embase, and Cochrane Library databases was conducted in November 2022. Longitudinal studies reporting HGS change after bariatric metabolic surgery were eligible. Pooled estimates for changes in HGS, body mass index (BMI), LM, and fat mass (FM) were calculated. Changes from baseline to the point closest to 6 months postoperatively were analyzed in trials with multiple follow-up examinations. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist. RESULTS: Three randomized controlled trials and seven prospective cohort studies involving 301 patients were included. Follow-up evaluations were conducted 6 months postoperatively in all trials except for two, whose follow-up visits were at 18 weeks and 12 months, respectively. Pooled analysis showed reduced BMI (- 10.8 kg/m2; 95% confidence interval: - 11.6 to - 9.9 kg/m2), LM (- 7.4 kg; - 9.3 to - 5.4 kg), and FM (- 22.3 kg; - 25.1 to - 19.6 kg) after bariatric metabolic surgery, whereas the change in HGS was not statistically significant (- 0.46 kg; - 1.76 to 0.84 kg). CONCLUSION: Despite the decreased body composition parameters, including muscle mass, strength was not impaired after bariatric metabolic surgery; this indicates that bariatric metabolic surgery is an effective weight management intervention that does not compromise strength.

Predictive value of the Framingham steatosis index for cardiovascular risk: a nationwide population-based cohort study.

Background: Non-alcoholic fatty liver disease (NAFLD) is common and is associated with cardiovascular (CV) disease and mortality. The Framingham steatosis index (FSI) was recently proposed as a diagnostic marker of NAFLD and was calculated from age, body mass index, triglyceride, aspartate aminotransferase, alanine aminotransferase, diabetes history, and hypertension status. We aimed to evaluate the predictive ability of FSI for CV risk using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Methods: Among 514,866 individuals in the NHIS-HEALS, we excluded those who died, had a history of admission due to a CV event, and were heavy drinkers. The final study cohort comprised 283,427 participants. We employed both unadjusted and covariate-adjusted models in Cox proportional hazards regression analyses to determine the association between FSI and major adverse cardiovascular events (MACEs), CV events, and CV mortality. Results: During a median follow-up of 5.9 years, we documented 9,674, 8,798, and 1,602 cases of MACEs, CV events, and CV mortality, respectively. The incidence of MACEs was 1.28%, 2.99%, 3.94%, and 4.82% in the first to fourth quartiles of FSI, respectively. The adjusted hazard ratios (95% confidence interval) for MACEs gradually and significantly increased with the FSI quartiles [1.302 (1.215-1.395) in Q2, 1.487 (1.390-1.590) in Q3, and 1.792 (1.680-1.911) in Q4], following an adjustment for conventional CV risk factors, including age, sex, smoking, drinking, physical activities, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and waist circumference. Participants in the higher quartiles of FSI exhibited a noteworthy increase in the occurrence of CV event. However, upon adjusting for relevant risk factors, the association between FSI and CV mortality did not reach statistical significance. Conclusion: Our study suggests that the FSI, which is a surrogate marker of NAFLD, has a prognostic value for detecting individuals at higher risk of CV events.

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice.

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity.

BACKGROUND/AIMS: To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. METHODS: This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. RESULTS: Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67, P<0.001; women: OR=1.59, 95% CI 1.40-1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02-1.50, P=0,028; women: OR=1.23, 95% CI 1.04-1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43-4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44-4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53-6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51-6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. CONCLUSION: In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

Association Between Insulin Resistance and Myosteatosis Measured by Abdominal Computed Tomography.

CONTEXT: Ectopic fat deposition in skeletal muscle, termed myosteatosis, is a key factor in developing insulin resistance. OBJECTIVE: This work aimed to evaluate the association between insulin resistance and myosteatosis in a large Asian population. METHODS: A total of 18 251 participants who had abdominal computed tomography were included in this cross-sectional study. Patients were categorized into 4 groups according to quartiles of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and intermuscular adipose tissue (IMAT). The absolute values of TAMA, NAMA, LAMA, and IMAT and the ratios of NAMA/BMI, LAMA/BMI, and NAMA/TAMA were used as myosteatosis indices. RESULTS: The absolute values of TAMA, NAMA, LAMA, and IMAT appeared to increase with higher HOMA-IR levels, and LAMA/BMI showed a similar upward trend. Meanwhile, the NAMA/BMI and NAMA/TAMA index showed downward trends. As HOMA-IR levels increased, the odds ratios (ORs) of the highest quartile of NAMA/BMI and NAMA/TAMA index decreased and that of LAMA/BMI increased. Compared with the lowest HOMA-IR group, the adjusted ORs (95% CI) in the highest HOMA-IR group for the lowest NAMA/TAMA quartile were 0.414 (0.364-0.471) in men and 0.464 (0.384-0.562) in women. HOMA-IR showed a negative correlation with NAMA/BMI (r = -0.233 for men and r = -0.265 for women), and NAMA/TAMA index (r = -0.211 for men and r = -0.214 for women), and a positive correlation with LAMA/BMI (r = 0.160 for men and r = 0.119 for women); P was less than .001 for all. CONCLUSION: In this study, a higher HOMA-IR level was significantly associated with a high risk of myosteatosis.

Association between Body Mass Index and Mortality in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: The association between body mass index (BMI) and mortality in patients with type 1 diabetes mellitus (T1DM) has been poorly examined and has never been systematically reviewed. This meta-analysis investigated the all-cause mortality risk for each BMI category among patients with T1DM. Methods: A systematic literature review of the PubMed, Embase, and Cochrane Library databases was performed in July 2022. Cohort studies comparing the mortality risk between BMI categories among patients with T1DM were eligible. Pooled hazard ratios (HRs) for all-cause mortality among underweight (BMI <18.5 kg/m2), overweight (BMI, 25 to <30 kg/m2), and obese (BMI ≥30 kg/m2) individuals were calculated in reference to the normal-weight group (BMI, 18.5 to <25 kg/m2). The Newcastle-Ottawa Scale was used to assess the risk of bias. Results: Three prospective studies involving 23,407 adults were included. The underweight group was shown to have a 3.4 times greater risk of mortality than the normal-weight group (95% confidence interval [CI], 1.67 to 6.85). Meanwhile, there was no significant difference in mortality risk between the normal-weight group and the overweight group (HR, 0.90; 95% CI, 0.66 to 1.22) or the obese group (HR, 1.36; 95% CI, 0.86 to 2.15), possibly due to the heterogeneous results of these BMI categories among the included studies. Conclusion: Underweight patients with T1DM had a significantly greater risk of all-cause mortality than their normal-weight counterparts. Overweight and obese patients showed heterogeneous risks across the studies. Further prospective studies on patients with T1DM are required to establish weight management guidelines.

Association between sarcopenic obesity and poor muscle quality based on muscle quality map and abdominal computed tomography.

OBJECTIVE: This study evaluated whether sarcopenic obesity is closely associated with muscle quality using abdominal computed tomography. METHODS: This cross-sectional study included 13,612 participants who underwent abdominal computed tomography. The cross-sectional area of the skeletal muscle was measured at the L3 level (total abdominal muscle area [TAMA]) and segmented into normal attenuation muscle area (NAMA, +30 to +150 Hounsfield units), low attenuation muscle area (-29 to +29 Hounsfield units), and intramuscular adipose tissue (-190 to -30 Hounsfield units). The NAMA/TAMA index was calculated by dividing NAMA by TAMA and multiplying by 100, and the lowest quartile of NAMA/TAMA index was defined as myosteatosis (<73.56 in men and <66.97 in women). Sarcopenia was defined using BMI-adjusted appendicular skeletal muscle mass. RESULTS: The prevalence of myosteatosis was found to be significantly higher in participants with sarcopenic obesity (17.9% vs. 54.2%, p < 0.001) than the control group without sarcopenia or obesity. Compared with the control group, the odds ratio (95% CI) for having myosteatosis was 3.70 (2.87-4.76) for participants with sarcopenic obesity after adjusting for age, sex, smoking, drinking, exercise, hypertension, diabetes, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. CONCLUSIONS: Sarcopenic obesity is significantly associated with myosteatosis, which is representative of poor muscle quality.

Stratification of Nontuberculous Mycobacterial Disease Risk in Type 2 Diabetes Based on Metformin Use: a Population-Based Cohort Study in South Korea.

In a 1:4 case-control matched analysis of data from a nationwide population-based cohort in South Korea, we evaluated whether metformin use mitigates the risk of nontuberculous mycobacterial disease in patients with type 2 diabetes. Multivariable analysis revealed no significant association of metformin use with a diminished risk for incident nontuberculous mycobacterial disease in patients with type 2 diabetes.

Sarcopenia in youth.

Recent research has revealed causes other than aging that may induce sarcopenia in young people, contrary to the long-studied age-dependent reduction in muscular mass and function. The risk of sarcopenia begins in early adulthood, resulting in exaggerated muscle dysfunction in later life. Despite its clinical significance, research on youth-onset sarcopenia is still in its infancy. Due to a paucity of epidemiologic data and standardized criteria for sarcopenia in youth, determining the prevalence of sarcopenia in the young population remains challenging. Based on the evidence, >1 in every 10 young adults of most ethnicities is estimated to have sarcopenia. This review summarizes the possible etiologies of sarcopenia in young populations, including metabolic syndrome, physical inactivity, inadequate nutrition, inherent and perinatal factors, vitamin D deficiency, endocrinopathy, an imbalance of gut microbiota, neuromuscular diseases, organ failure, malignancy, and other inflammatory disorders. This is the first review of the current knowledge on the importance, prevalence, diagnosis, and causes of sarcopenia in youth.

Type 2 Diabetes Mellitus- and Complication-Related Risk of Nontuberculous Mycobacterial Disease in a South Korean Cohort.

We aimed to investigate whether type 2 diabetes mellitus (T2DM) and diabetes-related complications constitute significant risk factors for nontuberculous mycobacterial (NTM) disease. Data from the National Health Insurance Service-National Sample Cohort (which represents 2.2% of the total South Korean population) recorded between 2007 and 2019 were extracted to establish the NTM-naive T2DM cohort (n = 191,218) and the 1:1 age- and sex-matched NTM-naive matched cohort (n = 191,218). Intergroup comparisons were performed to determine differences in the NTM disease risk of the two cohorts during the follow-up period. During median follow-up of 9.46 and 9.25 years, the incidence of NTM disease was 43.58/100,000 and 32.98/100,000 person-years in the NTM-naive T2DM and NTM-naive matched cohorts, respectively. Multivariable analysis showed that T2DM alone did not confer a significant risk for incident NTM disease, although T2DM with ≥2 diabetes-related complications significantly increased NTM disease risk (adjusted hazard ratio [95% confidence interval], 1.12 [0.99 to 1.27] and 1.33 [1.03 to 1.17], respectively). In conclusion, the presence of T2DM with ≥2 diabetes-related complications significantly increases the risk for NTM disease. IMPORTANCE We assessed whether patients with T2DM are at higher risk for incident NTM disease through analysis of NTM-naive matched cohorts from the data of a national population-based cohort which represents 2.2% of the total South Korean population. Although T2DM alone is not a statistically significant risk factor for NTM disease, T2DM significantly increases the risk of NTM disease in those with ≥2 diabetes-related complications. This finding suggested that patients with T2DM with a larger number of complications should be considered a high-risk group for NTM disease.

Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography.

BACKGROUND: The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. METHODS: Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. RESULTS: According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). CONCLUSION: A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Association between hypertension and myosteatosis evaluated by abdominal computed tomography.

Few studies have examined the relationship between myosteatosis and hypertension, and no studies have enrolled an Asian population. Existing studies also found discordant results, possibly due to the use of conventional myosteatosis indices that are not sufficiently reliable and representative. Therefore, we investigated the association between myosteatosis and hypertension in Asian individuals using novel, objective computed tomography (CT) markers. The total abdominal muscle area (TAMA) was determined from abdominal CT scans taken at the L3 level. Based on the mean CT attenuation, the TAMA was divided into intramuscular adipose tissue and skeletal muscle area (SMA), which was further segmented into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). Among SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and the NAMA/TAMA index, NAMA/BMI was chosen through receiver operating characteristic curves as the best predictive marker for hypertension. The hypertension risk for each quartile of NAMA/BMI was calculated by logistic regression analysis. Among the 19,766 participants, 40.3% of men and 23.8% of women had hypertension. People with hypertension showed unhealthier myosteatosis profiles than normotensive controls. Similarly, a lower NAMA/BMI was significantly associated with a greater hypertension risk. The lowest quartile group of NAMA/BMI exhibited 2.3- and 2.6-fold higher risks of hypertension than the highest quartile in men and women, respectively. In conclusion, advanced myosteatosis assessed by abdominal CT was significantly correlated with a higher risk of hypertension. Improving myosteatosis may be a new approach for preventing cardiovascular diseases, including hypertension. Advanced myosteatosis measured by abdominal CT taken at the L3 level was significantly correlated with a higher risk of hypertension even after adjusting for health behaviors, intake of lipid-lowering drugs, plasma lipid levels, and other ectopic fat distribution.

Association of serum gamma-glutamyl transferase with myosteatosis assessed by muscle quality mapping using abdominal computed tomography.

PURPOSE: Myosteatosis, which is associated with a variety of cardiometabolic illnesses, represents muscle quality, an important aspect of sarcopenia. A new laboratory marker for myosteatosis has been required to more readily identify it. We investigated whether serum gamma-glutamyl transferase (GGT) levels are associated with myosteatosis measured by computed tomography (CT). METHODS: The total abdominal muscle area (TAMA) of 13,452 subjects was measured at the L3 level with abdominal CT. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and NAMA/TAMA. Logistic regression analysis was used to examine the odds ratio (OR) of each GGT quartile for the highest quartile of myosteatosis indices in each sex. RESULTS: The mean age and serum GGT levels were 53.7 years and 32.8 IU/L (standard deviation [SD], 37.6), respectively, in men, and 53.2 years and 18.4 IU/L (SD, 19.8) in women. In both sexes, the ORs of all myosteatosis indices differed significantly between GGT quartiles. Indices of good- and poor-quality muscle were negatively and positively correlated with GGT levels, respectively. CONCLUSION: Higher GGT levels were significantly associated with advanced myosteatosis defined by reliable CT indices. This result opens the possibility for using GGT as a cost-effective indicator of myosteatosis. Further prospective research on changes to GGT levels with myosteatosis alleviation will validate GGT as a monitoring marker.

Angiogenic adipokine C1q-TNF-related protein 9 ameliorates myocardial infarction via histone deacetylase 7-mediated MEF2 activation.

C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine and has high potential as a therapeutic target. However, the role of CTRP9 in cardiovascular disease pathogenesis remains unclear. We found CTRP9 to induce HDAC7 and p38 MAPK phosphorylation via tight regulation of AMPK in vascular endothelial cells, leading to angiogenesis through increased MEF2 activity. The expression of CTRP9 and atheroprotective MEF2 was decreased in plaque tissue of atherosclerotic patients and the ventricle of post-infarction mice. CTRP9 treatment inhibited the formation of atherosclerotic plaques in ApoE KO and CTRP9 KO mice. In addition, CTRP9 induced significant ischemic injury prevention in the post-MI mice. Clinically, serum CTRP9 levels were reduced in patients with MI compared with healthy controls. In summary, CTRP9 induces a vasoprotective response via the AMPK/HDAC7/p38 MAPK pathway in vascular endothelial cells, whereas its absence can contribute to atherosclerosis and MI. Hence, CTRP9 may represent a valuable therapeutic target and biomarker in cardiovascular diseases.