Ascochlorin Attenuates the Early Stage of Adipogenesis via the Wnt/ß-Catenin Pathway and Inhibits High-Fat-Diet-Induced Obesity in Mice.

This study investigated the effects of ascochlorin (ASC), a natural compound derived from the fungus Ascochyta viciae, on adipogenesis and obesity. We determined the effects of ASC on 3T3-L1 preadipocytes and whether it ameliorated to mitigate high-fat diet (HFD)-induced obesity in C57BL/6J mice. We found that ASC significantly inhibited the differentiation of preadipocytes by modulating the Wnt/ß-catenin signaling pathway, a key regulator of adipogenic processes. Treatment with ASC not only reduced the mRNA and protein expression of key adipogenic transcription factors such as C/EBPα and PPARγ, but also reduced lipid accumulation both in vitro and in vivo. In addition, treatment HFD-fed mice with ASC significantly reduced their weight gain and adiposity vs. control mice. These results suggest that ASC has considerable potential as a therapeutic agent for obesity, owing to its dual action of inhibiting adipocyte differentiation and reducing lipid accumulation. Thus, ASC represents a promising candidate as a natural anti-obesity agent.

The association of fatty liver index and metabolic syndrome with cardiovascular outcomes, liver-related mortality, and all-cause mortality: a nationwide cohort study.

We investigated the risk of cardiovascular events, all-cause mortality, and liver-related mortality according to the presence of metabolic syndrome (MetS) and fatty liver index (FLI). In this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2009 to 2012. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥ 60. Risk of all-cause mortality, liver-related mortality, and major adverse cardiovascular events (MACE) including myocardial infarction (MI), stroke, heart failure (HF), and cardiovascular disease (CVD)-related mortality was assessed according to the presence of MetS and FLI among adults (aged 40 to 80 years) who underwent health examinations (n = 769,422). During a median 8.59 years of follow up, 44,356 (5.8%) cases of MACE, 24,429 (3.2%) cases of all-cause mortality, and 1114 (0.1%) cases of liver-related mortality were detected in the entire cohort. When the FLI < 30 without MetS group was set as a reference, the FLI ≥ 60 with MetS group had the highest risk of MACE (adjusted hazard ratio [aHR] 2.05, 95% confidence interval [CI] 1.98-2.13) and all-cause mortality (aHR 1.96, 95% CI 1.86-2.07). The risk of liver-related mortality (aHR 10.71, 95% CI 8.05-14.25) was highest in the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group had a higher risk of MACE (aHR 1.39, 95%CI 1.28-1.51), a lower risk of liver-related mortality (aHR 0.44, 95%CI 0.33-0.59), and no significant difference in all-cause mortality compared with the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group was associated with the highest risk of MACE and the FLI ≥ 60 without MetS group had the highest risk liver-related mortality, but there was no significant difference in all-cause mortality between two groups. In conclusion, as FLI levels increase, the risk of MACE increases, and the risk increases additively in the presence of MetS. The risk of liver-related mortality increases with higher FLI levels, the effect of high FLI on increased risk is more significant in groups without MetS compared to those with MetS.

Association between weight loss and cardiovascular outcomes and mortality in Korea: A nationwide cohort study.

AIMS: While the benefit of weight loss in reducing the incidence of cardiovascular disease (CVD) is recognized, its association with CVD mortality remains controversial. This study investigates the association between weight loss and the incidence of CVD outcomes. METHODS: This was a 7.2-year retrospective cohort study of 1,020,533 adults aged 40-80 years who underwent at least two general health checkups within a 2-year interval in Korea. Weight was measured by trained examiners at certified hospitals. We used Cox proportional hazards models to examine the association between weight loss and the incidence of CVD outcomes. RESULTS: Weight loss of more than 3 % was associated with an increased risk of combined CVD events (hazard ratio [HR] for moderate weight loss: 1.24, 95 % confidence interval [CI]: 1.21-1.28; HR for severe weight loss: 1.45, 95 % CI: 1.33-1.57). Weight loss was significantly associated with an increased risk of both nonfatal CVD events and CVD mortality, but regular exercise mitigated the adverse effects on CVD mortality. CONCLUSIONS: Weight loss of more than 3% is associated with an increased risk of a combined CVD events, consistent across most risk factors. However, regular exercise may reduce the adverse effects on CVD mortality, suggesting a potential protective role of physical activity.

Risk of Depression according to Cumulative Exposure to a Low-Household Income Status in Individuals with Type 2 Diabetes Mellitus: A Nationwide Population- Based Study.

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

Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD.

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

Low Household Income Status and Death from Pneumonia in People with Type 2 Diabetes Mellitus: A Nationwide Study.

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

Association of body weight change with all-cause and cause-specific mortality: A nationwide population-based study.

AIMS: Weight gain and loss increase the risk of all-cause mortality. This study explored the association of short-term weight change with all-cause and cause-specific mortality in middle-aged to older people. METHODS: This was a 8.4-year retrospective cohort study of 645,260 adults aged 40 to 80 who underwent health checkups twice within a 2-year interval between January 2009 and December 2012. Cox analyses were used to analyze the association between short-term weight change and all-cause and cause-specific mortality. RESULTS: Weight gain and loss were associated with an increased risk of all-cause mortality: the hazard ratios were 2.05 (95% confidence interval [CI], 1.93-2.16), 1.21 (95% CI, 1.16-1.25), 1.12 (95% CI 1.08-1.17), and 1.60 (95% CI, 1.49-1.70) for the severe weight loss, moderate weight loss, moderate weight gain, and severe weight gain groups, respectively. This U-shaped association was also seen between weight change and cause-specific mortality. Within the weight loss group, those who regained weight after two years had a reduced mortality risk. CONCLUSIONS: In a middle-aged and elderly population, weight gain or loss of more than 3% during a 2-year interval was related to an elevated risk of all-cause and cause-specific mortality.

Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019.

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

MAFLD and NAFLD in the prediction of incident chronic kidney disease.

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