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.

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 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.

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 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.

Durability of glucose-lowering effect of dulaglutide in patients with type 2 diabetes mellitus: A real-world data study.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease requiring lifelong treatment, and durable medication is essential for maintaining stable glycemic control. This study aimed to evaluate the long-term efficacy of dulaglutide in participants who have continued the drug for more than one year. Methods: We conducted a retrospective study on 605 participants, who used dulaglutide for over one year between 2016 and 2020. Changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose, and bodyweight from baseline to last prescription day were assessed. Adherence was evaluated by the proportion of days covered (PDC), and a PDC value ≥ 0.80 was considered adherent. Results: The mean age was 54.0 ± 11.1 years, and 46.1% were female. The mean baseline HbA1c, bodyweight, and duration of diabetes were 8.8% (72.7 mmol/mol), 75.6 kg, and 12.2 years, respectively. During the mean follow-up of 33.1 months, HbA1c and bodyweight decreased by 1.28% (14 mmol/mol, P < 0.001) and by 3.19 kg (P < 0.001), respectively. The participants were highly adherent with PDC ≥ 0.80 in 92.4% of the participants. Conclusion: In T2DM patients, long-term dulaglutide treatment was effective in maintaining HbA1c and weight reduction. Dulaglutide could be a favorable option of long-term treatment in real-world clinical practice.

Implications of metabolic health status and obesity on the risk of kidney cancer: A nationwide population-based cohort study.

Purpose: This study evaluated the association between metabolic health status and incident kidney cancer among obese participants. Materials and methods: A total of 514,866 individuals were included from the Korean National Health Insurance Service-National Health Screening Cohort. Changes in metabolic health status and obesity from the baseline examination in 2009-2010 to the next biannual examination in 2011-2012 were determined. Based on the status change, obese participants were divided into four groups: stable metabolically healthy obesity, metabolically healthy obesity to metabolically unhealthy obesity, metabolically unhealthy obesity to metabolically healthy obesity, and stable metabolically unhealthy obesity. Results: The stable metabolically healthy obesity phenotype did not confer an increased risk of incident kidney cancer, compared to the stable metabolically healthy non-obese group. In contrast, the metabolically healthy obesity to metabolically unhealthy obesity group had a significantly higher risk of incident kidney cancer than the stable metabolically healthy non-obese group. Among patients with metabolically unhealthy obesity at baseline, those who transitioned to the metabolically healthy obese group had no increased risk of kidney cancer, whereas those who remained in metabolically unhealthy obesity status had a higher risk of incident kidney cancer than the stable metabolically healthy non-obese group. The transition or maintenance of metabolic health was a decisive factor for kidney cancer in obese patients. Conclusions: Maintaining or restoring metabolic health should be stressed upon in obese patients to reduce the risk of kidney cancer.

Free Versus Fixed-Ratio Combination of Basal Insulin and GLP-1 Receptor Agonists in Type 2 Diabetes Uncontrolled With GLP-1 Receptor Agonists: A Systematic Review and Indirect Treatment Comparison.

Introduction: This study evaluates the efficacy and safety of the free up-titration of basal insulin and fixed-ratio combination (FRC) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients inadequately controlled with GLP-1RA. Methods: With the use of a systematic literature review of PubMed, Embase, Web of Science, and the Cochrane Library databases through July 2021, randomized controlled trials that compared the free up-titration or FRC with remaining on GLP-1RA in T2DM patients uncontrolled with GLP-1RA were included. A comparison of adding basal insulin to maintaining GLP-1RA and an indirect comparison between the two strategies were conducted on the change in HbA1c, fasting plasma glucose (FPG), target achievement [HbA1c < 7.0%], and the risk of confirmed hypoglycemia. The Cochrane Collaboration's tool was used to assess the risk of bias. Results: Two free up-titration and two FRC trials involving 1,612 participants, all lasting 26 weeks, were included. Both approaches significantly lowered HbA1c levels (weighted mean difference [WMD] -0.75%, 95% CI -0.97 to -0.53) but increased hypoglycemic risk [risk ratio (RR) 7.59, 95% CI 3.35-17.17] compared to the unchanged GLP-1RA. No significant differences were discovered between the two methods regarding the decrease in HbA1c (WMD 0.08%, 95% CI -1.07% to 1.23%), FPG (WMD -2.29 mg/dl, 95% CI -45.07 to 40.49 mg/dl), target achievement (RR 1.03, 95% CI 0.50-2.14), and hypoglycemic risk (RR 0.32, 95% CI 0.03-3.59). Conclusion: In patients who failed to reach target HbA1c levels despite the GLP-1RA treatment, both strategies of adding basal insulin, free up-titration and FRC, are comparable options are comparable options.

Triglyceride-Glucose Index Is a Useful Marker for Predicting Future Cardiovascular Disease and Mortality in Young Korean Adults: A Nationwide Population-Based Cohort Study.

Objective: The triglyceride-glucose (TyG) index, the product of fasting triglycerides and glucose, is a useful and cost-effective marker of insulin resistance (IR). Furthermore, the TyG index is a known IR screening tool in healthy young adults but not in those with atherosclerotic cardiovascular disease (CVD). Thus, this study aimed to evaluate the TyG index as a predictor of CVD in healthy young adults. Methods: This study enrolled 6,675,424 adults aged 20-39 years without CVD from the National Health Information Database. We categorized them by TyG index quartile from 2009-2017. The study outcomes were stroke, myocardial infarction (MI), and mortality. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates. Results: During a mean 7.4 years of follow-up, 8,506 cases of stroke, 12,312 cases of MI, and 22,667 deaths were recorded. Multivariable-adjusted hazard ratios (HRs) for participants in the highest TyG index quartile demonstrated that they were at higher risk for stroke (HR, 1.253; 95% confidence interval [CI], 1.167-1.346), MI (HR, 1.258; 95% CI, 1.187-1.334), and mortality (HR, 1.151; 95% CI, 1.104-1.200) than those in the lowest TyG index quartile independent of age, sex, smoking, alcohol consumption, physical activity, income, body mass index, blood pressure, and total cholesterol. The HRs for outcomes in the highest quartiles were higher when the TyG index was applied than when triglyceride or fasting glucose alone was applied. Conclusion: TyG index, a simple measure reflecting IR, can predict CVD and mortality in young and healthy populations.

Triglyceride-Glucose Index Predicts Cardiovascular Outcome in Metabolically Unhealthy Obese Population: A Nationwide Population-Based Cohort Study.

Background: This study assesses the prognostic value of the triglyceride-glucose (TyG) index for cardiovascular (CV) risk in subgroups based on metabolic health and obesity status. Methods: Originally, 514,866 participants were enrolled from the Korean National Health Insurance Service-National Health Screening Cohort. The study participants were categorized into four groups: metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). The TyG index was calculated using the following formula: ln (fasting triglyceride [mg/dL]×fasting plasma glucose [mg/dL]/2). Participants were followed from 2009 to 2015 for CV events and CV mortality according to the TyG index. Results: After exclusions, the final study cohort contained 292,206 people. During the follow-up, 9,138 CV events and 1,163 CV deaths were documented. When the high and low TyG groups were compared, the high TyG group had a substantially increased risk of CV events among the MUNO and MUO participants (multivariable-adjusted hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.30 and 1.27 [1.14-1.42], respectively). In participants with MUO status, CV mortality was also significantly increased in the high TyG group compared with the corresponding low TyG group (multivariable-adjusted HR, 1.48; 95% CI, 1.13-1.93). In contrast, a high TyG index was not related to CV mortality in the MHNO, MHO, and MUNO groups. Conclusion: The predictive value of the TyG index can vary across populations. Among MUO participants, the TyG index was significantly and positively correlated with unfavorable CV outcomes.

Association of the atherogenic index of plasma with cardiovascular risk beyond the traditional risk factors: a nationwide population-based cohort study.

BACKGROUND: The atherogenic index of plasma (AIP) is composed of triglycerides and high-density lipoprotein cholesterol and is a novel marker for assessing the risk of atherogenicity and cardiometabolic health. An association between AIP and greater frequency of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus and high cardiovascular (CV) disease risk has been reported. However, only few studies have examined the correlation between AIP and CV risk in general populations. We thus aimed to evaluate the relationship between AIP and CV diseases using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). METHODS: A total of 514,866 participants were enrolled from the NHIS-HEALS and classified according to the AIP quartiles. We performed univariate and multivariate Cox proportional hazards regression analyses to determine the association between AIP and MACEs, CV events, and CV mortality. RESULTS: During follow-up, we documented 12,133, 11,055, and 1942 cases of MACEs, CV events, and CV mortality, respectively. The multivariate-adjusted hazard ratios [HRs; 95% confidence interval (CI)] for MACEs gradually and significantly increased with the AIP quartiles [1.113 (1.054-1.175) in Q2, 1.175 (1.113-1.240) in Q3, and 1.278 (1.209-1.350) in Q4], following an adjustment for the conventional CV risk factors, including age, sex, body mass index, smoking, alcohol drinking, physical activities, household income, fasting glucose, systolic blood pressure, low-density lipoprotein cholesterol, and estimated glomerular filtration rate. In subgroup analyses, the association of AIP with MACEs and CV events was particularly outstanding in patients with diabetes. CONCLUSIONS: AIP was significantly associated with CV risks after adjusting for the traditional risk factors. Therefore, it may be used as an effective mass screening method to identify patients at a high risk of CV events.

Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM). METHODS: A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline. RESULTS: During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm2 and 1.08 in men, respectively, and 85.7 cm2 and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively. CONCLUSION: Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm2 or VSR ≥1.0 in men; VFA ≥85 cm2 or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m2, and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was -2.8 kg (95% CI, -4.21 to -1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

Prognostic Value of Triglyceride and Glucose Index for Incident Type 2 Diabetes beyond Metabolic Health and Obesity.

BACKGROUND: Metabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index. METHODS: The study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group. RESULTS: During the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively. CONCLUSION: MHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

The risk of Alzheimer's disease according to dynamic changes in metabolic health and obesity: a nationwide population-based cohort study.

We evaluated the association of metabolic health and obesity phenotypes with the risk of Alzheimer's disease (AD). This study enrolled 136,847 elderly participants aged 60 or above from the Korean National Health Insurance System. At baseline examinations in 2009 and 2010, subjects were categorized into four groups: the metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO) groups. Based on the phenotypic transition after 2 years, the subjects were further categorized into 16 subgroups. They were followed from 2009 to 2015 to monitor for AD development. The MHO phenotype protected subjects from AD, relative to the MHNO phenotype (HR, 0.73; 95% CI, 0.65-0.81). Among subjects initially classified as MHO, 41.8% remained MHO, with a significantly lower risk of AD compared with the stable MHNO group (HR, 0.62; 95% CI, 0.50-0.77). Among MUO subjects at baseline, those who changed phenotype to MUNO were at higher risk of AD (HR, 1.47; 95% CI, 1.28-1.70), and the transition to the MHO phenotype protected subjects from AD (HR, 0.62; 95% CI, 0.50-0.78). The MHO phenotype conferred a decreased risk of AD. Maintenance or recovery of metabolic health might mitigate AD risk among obese individuals.

Switching from insulin to dulaglutide therapy in patients with type 2 diabetes: A real-world data study.

AIM: Patients with type 2 diabetes (T2DM) who require injectable therapy have been conventionally treated with insulin. A glucagon-like peptide 1 receptor agonist was recently recommended as first-line injectable treatment, but few studies have investigated the effects of switching from insulin to dulaglutide. This study investigated the clinical efficacy and parameters affecting responses to dulaglutide as an alternative to insulin in patients with T2DM in a real-world clinical setting. METHODS: Ninety-eight patients with T2DM who were switched from insulin to dulaglutide therapy were retrospectively evaluated. Changes in HbA1c concentrations were assessed after 6 months of consistent treatment with dulaglutide. Multiple linear regression analysis was performed to evaluate parameters affecting the response to dulaglutide treatment. RESULTS: After treatment with dulaglutide for 6 months, patients experienced changes in HbA1c of -0.95% (95% confidence interval [CI]: -1.30% to -0.59%, P < 0.001) and in body weight of -1.75 kg (95% CI: -2.42 to -1.08 kg, P < 0.001). Multiple linear regression analysis showed that higher baseline HbA1c was significantly associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms. CONCLUSION: Switching from insulin to dulaglutide can lead to significant improvement in HbA1c levels and body weight ​reduction in T2DM patients over 6 months. Higher baseline HbA1c is associated with a better clinical response to dulaglutide.

Differential Effect of Metabolic Health and Obesity on Incident Heart Failure: A Nationwide Population-Based Cohort Study.

Background: Metabolically healthy obese (MHO) individuals and their association with cardiometabolic diseases have remained controversial. We aimed to explore the risk of incident heart failure (HF) based on the baseline metabolic health and obesity status as well as their transition over 2 years. Methods: The Korean National Health Insurance Service-National Health Screening Cohort data of 514,886 participants were analyzed. Obesity was defined as BMI ≥25 kg/m2 according to the Korean Centers for Disease Control and Prevention. The metabolic health and obesity status were evaluated at baseline and after two years. Study participants were followed to either the date of newly diagnosed HF or the last follow-up visit, whichever occurred first. Results: The MHO group comprised 9.1% of the entire population and presented a better baseline metabolic profile than the metabolically unhealthy non-obese (MUNO) and metabolicavlly unhealthy obese (MUO) groups. During the median 71.3 months of follow-up, HF developed in 5,406 (1.5%) participants. The adjusted hazard ratios [HRs (95% CI)] of HF at baseline compared with the metabolically healthy non-obese (MHNO) group were 1.29 [1.20-1.39], 1.37 [1.22-1.53], and 1.63 [1.50-1.76] for MUNO, MHO, and MUO groups, respectively. With the stable MHNO group as reference, transition into metabolically unhealthy status (MUNO and MUO) increased the risk of HF, regardless of the baseline status. Subjects who were obese at both baseline and follow-up showed an increased risk of HF, regardless of their metabolic health status. Conclusions: Metabolic health and obesity status and their transition can predict the risk of incident HF. Losing metabolic health in baseline non-obese and obese individuals and remaining obese in baseline obese individuals showed a significantly increased risk of incident HF. Maintaining good metabolic health and a lean body may prevent the development of HF.

Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review.

Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], -0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice.

Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown adipocyte-specific deletion of pink1, a Parkinson disease-related gene involved in selective mitochondrial autophagy (mitophagy), induced BAT dysfunction, and obesity-prone type in mice. Defective mitochondrial function is among the upstream signals that activate the NLRP3 inflammasome. NLRP3 was induced in brown adipocyte precursors (BAPs) from pink1 knockout (KO) mice. Unexpectedly, NLRP3 induction did not induce canonical inflammasome activity. Instead, NLRP3 induction led to the differentiation of pink1 KO BAPs into white-like adipocytes by increasing the expression of white adipocyte-specific genes and repressing the expression of brown adipocyte-specific genes. nlrp3 deletion in pink1 knockout mice reversed BAT dysfunction. Conversely, adipose tissue-specific atg7 KO mice showed significantly lower expression of Nlrp3 in their BAT. Overall, our data suggest that the role of mitophagy is different from general autophagy in regulating adipose tissue and whole-body energy metabolism. Our results uncovered a new mitochondria-NLRP3 pathway that induces BAT dysfunction. The ability of the nlrp3 knockouts to rescue BAT dysfunction suggests the transcriptional function of NLRP3 as an unexpected, but a quite specific therapeutic target for obesity-related metabolic diseases.Abbreviations: ACTB: actin, beta; BAPs: brown adipocyte precursors; BAT: brown adipose tissue; BMDMs: bone marrow-derived macrophages; CASP1: caspase 1; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; ChIP: chromatin immunoprecipitation; EE: energy expenditure; HFD: high-fat diet; IL1B: interleukin 1 beta; ITT: insulin tolerance test; KO: knockout; LPS: lipopolysaccharide; NLRP3: NLR family, pyrin domain containing 3; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RD: regular diet; ROS: reactive oxygen species; RT: room temperature; UCP1: uncoupling protein 1 (mitochondrial, proton carrier); WT: wild-type.