Effects of weight loss on metabolic dysfunction-associated fatty liver disease in Japanese people: Non-alcoholic fatty liver disease in the Gifu area, longitudinal analysis study.

AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern. This cohort study aimed to evaluate the association between weight loss and remission of MAFLD in the Japanese population to aid the development of efficient treatment strategies. METHODS: This retrospective cohort study was conducted at a Japanese health screening center. Participants included 3309 individuals diagnosed with baseline MAFLD between 2004 and 2016. Logistic regression analysis was used to assess the association between MAFLD remission from baseline to 5 years and weight change. RESULTS: After 5 years, 671 participants achieved MAFLD remission. Weight loss was associated with MAFLD remission for every 1 kg of weight loss over 5 years; the odds ratio for MAFLD remission was 1.24 (95% CI 1.15-1.34) for participants with type 2 diabetes, 1.40 (95% CI 1.35-1.45) for overweight participants, and 1.51 (95% CI 1.33-1.72) for non-overweight participants with metabolic dysfunctions. The cutoff values for weight loss for MAFLD remission were 1.9 kg for all participants, 3.0 kg for participants with type 2 diabetes, 1.9 kg for overweight participants, and 0.8 kg for non-overweight participants with metabolic dysfunctions. CONCLUSIONS: Among participants diagnosed with MAFLD, weight loss was associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The results of this study may contribute to the development of novel approaches to achieve MAFLD remission.

U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.

Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.

Amyloid precursor protein 770 is specifically expressed and released from platelets.

Platelets not only play an essential role in hemostasis after vascular injury but are also involved in the development of coronary artery disease (CAD) and cerebrovascular lesions. Patients with CAD and cerebral ischemia are recommended to undergo antiplatelet therapy, but they have an increased incidence of major bleeding complications. Both assessment of the platelet activation status and response to antiplatelet therapy in each patient are highly desired. ß-Amyloid precursor protein (APP) 770 is expressed in vascular endothelial cells, and its extracellular region, a soluble form of APP770 (sAPP770, also called nexin-2), is proteolytically cleaved for shedding. Abundant sAPP770 is also released from activated platelets. In this study, we used peripheral blood samples from patients with CAD and control subjects and evaluated sAPP770 as a specific biomarker for platelet activation. First, the plasma levels of sAPP770 correlated well with those of the soluble form CD40 ligand (CD40L), an established biomarker for platelet activation. Additionally, flow cytometry analysis using peripheral blood cells showed that CD40L expression is up-regulated in activated T cells, whereas APP770 expression is negligible in all blood cell types except platelets. Following stimulation with collagen or ADP, aggregating platelets immediately released sAPP770. Finally, patients with dual antiplatelet therapy showed significantly lower levels of plasma sAPP770 than those with no therapy. Taken together, our data show that plasma sAPP770 could be a promising biomarker for platelet activation.

Clinical characteristics and longitudinal changes of patients with non-alcoholic fatty liver disease in 2 decades: the NAGALA study.

BACKGROUND: In this study, to clarify the evolving background of people with non-alcoholic fatty liver disease (NAFLD), we compared the current prevalence of NAFLD with that of 2 decades ago. METHODS: We included two cohorts. The past cohort was from 1994 to 1997 and included 4279 men and 2502 women. The current cohort was from 2014 to 2017 and included 8918 men and 7361 women. NAFLD was diagnosed by abdominal ultrasonography. RESULTS: The prevalence of NAFLD increased in both genders throughout these 2 decades (18.5% in the past cohort and 27.1% in the current cohort for men; and 8.0% in the past cohort and 9.4% in the current cohort for women). The prevalence of hyperglycemia increased, whereas the prevalence of low high-density lipoprotein cholesterol levels and hypertriglyceridemia significantly decreased. There was no significant difference in the mean body mass index. Multivariate analysis revealed that the prevalence of obesity and body mass index were significantly associated with the prevalence of NAFLD in both the past and current cohorts. CONCLUSIONS: The incidence of NAFLD significantly increased throughout these 2 decades, and obesity is the most prevalent factor. Thus, body weight management is an essential treatment option for NAFLD.

Obesity and metabolic abnormalities as risks of alcoholic fatty liver in men: NAGALA study.

BACKGROUND: Hepatic steatosis has a pivotal role in the development of chronic liver diseases, even in alcohol-related liver disease. Alcoholic fatty liver disease is an important phenotype among alcohol-related liver diseases. While metabolic syndrome is a dominant risk factor of incident nonalcoholic fatty liver disease, the role of metabolic syndrome in alcoholic fatty liver disease has not been clarified yet. METHODS: A retrospective cohort study was performed at a health check-up center in Japan. Subjects consisted of male participants without fatty liver who consumed ethanol of 420 g/week or higher. Adjusted hazard ratios and 95% confidence intervals at the baseline examinations for incident alcoholic fatty liver disease were estimated using Cox model. RESULTS: A total of 640 participants were included in this study. During 3.91 years (IQR 1.63-7.09) of follow-up, 168 new cases of alcoholic fatty liver disease developed (49.1 cases per 1000 persons per year). After adjustment for age, smoking status, alcohol consumption, the hazard ratio for a 1 kg/m2 increase in body mass index was 1.2 (1.12-1.28). The hazard ratio of subjects with high triglyceride and low high-density lipoprotein-cholesterol levels were 1.56 (1.12-2.18) and 1.52 (1.03-2.25), respectively. CONCLUSIONS: Obesity, high triglyceridemia, and low high-density lipoprotein-cholesterolemia are independent risk factors of alcoholic fatty liver disease in Japanese men who consumed alcohol habitually. In people with these risks, triglyceride lowering and high-density lipoprotein-cholesterol raising by improving insulin resistance and weight maintenance in addition to abstinence from alcohol would be effective in preventing the development of alcoholic fatty liver disease.

Benefits of linked color imaging for recognition of early differentiated-type gastric cancer: in comparison with indigo carmine contrast method and blue laser imaging.

BACKGROUND AND AIM: Linked color imaging (LCI) is a novel endoscopy system, which enhances slight differences in mucosal color. However, whether LCI is more useful than other kinds of image-enhanced endoscopy (IEE) in recognizing early gastric cancer remains unclear. This study aimed to evaluate LCI efficacy compared with the indigo carmine contrast method (IC), and blue laser imaging-bright (BLI-brt) in early differentiated-type gastric cancer recognition. METHODS: We retrospectively analyzed early differentiated-type gastric cancer, which were examined by all four imaging techniques (white light imaging, IC, LCI, BLI-brt) at Asahi University Hospital from June 2014 to November 2018. Both subjective evaluation (using ranking score: RS) and objective evaluation (using color difference score: CDS) were adopted to quantify early differentiated-type gastric cancer recognition. RESULTS: During this period, 87 lesions were enrolled in this study. Both RS and CDS of LCI were significantly higher (p < 0.01) than those of IC and BLI-brt. Both RS and CDS of BLI-brt had no significant difference compared with those of IC. Subgroup analysis revealed that LCI was especially useful in post-Helicobacter pylori eradication patients and flat or depressed lesions compared with IC and BLI-brt. CONCLUSIONS: LCI appears to be more beneficial for the recognition of early differentiated-type gastric cancer in endoscopic screenings than IC and BLI-brt from the middle to distant view.

Creatinine-to-bodyweight ratio is a predictor of incident non-alcoholic fatty liver disease: A population-based longitudinal study.

AIM: Serum creatinine (Cre) is used as a surrogate marker of muscle mass. We investigated the impact of the Cre-to-bodyweight (BW) ratio (Cre/BW) on incident non-alcoholic fatty liver disease (NAFLD). METHODS: Fatty liver disease was diagnosed by abdominal ultrasonography. In this historical cohort study of 13 728 participants (6397 men and 7331 women), we divided the participants into two groups by sex and into quartiles according to Cre (mg/dL)/BW (kg; Q1-4). We carried out Cox proportional hazard models, adjusting for age, alanine aminotransferase, fasting plasma glucose, systolic blood pressure, alcohol consumption, smoking status, and exercise. RESULTS: During the 5.1-year follow up for men and 6.0-year follow up for women, 2497 participants (1696 men, 801 women) developed NAFLD. The 4000-days cumulative incidence rates of FLD for men and women were 29.6% and 16.6% in Q1, 28.2% and 10.6% in Q2, 25.5% and 8.8% in Q3, and 22.7% and 7.7% in Q4, respectively. The hazard ratios of incident NAFLD in Q1 (Cre/BW [×100]: men <1.28; women <1.17) were 1.89 (95% confidence interval 1.64-2.17, P < 0.001) in men and 2.96 (2.42-3.62, P < 0.001) in women, compared with Q4 (Cre/BW [×100]: men ≥1.61; women ≥1.51). CONCLUSIONS: A low Cre/BW is associated with an increased risk of NAFLD. Screening Cre/BW can be used to identify individuals who are at high risk of NAFLD.

Triglyceride-glucose index (TyG index) is a predictor of incident colorectal cancer: a population-based longitudinal study.

BACKGROUND: Colorectal cancer (CRC), which is related with insulin resistance, is a one of the most common cancers. Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We conducted the investigation of association between TyG index and incident CRC. METHODS: We examined the affect of TyG index on incident CRC in this historical cohort study of 27,944 (16,454 men and 11,490 women) participants. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The impact of TyG index on incident CRC was investigated using Cox proportional hazard models, adjusting for sex, age, body mass index, smoking status, alcohol consumption, exercise, systolic blood pressure and creatinine. The covariate-adjusted receiver operating characteristic (ROC) curve calculated the area under the curve (AUC) and cut-off value of TyG index for the incidence of CRC. RESULTS: During the median 4.4-year follow-up, 116 participants were diagnosed as CRC. The cumulative incidence rate of CRC were 0.4%. In Cox proportional hazard model, the HRs of TyG index were 1.38 (95% Confidence interval (CI), 1.00-1.91, p = 0.049) after adjusting for covariates. In the covariate-adjusted ROC curve analysis, the cut-off value of TyG index for incident CRC was 8.272 (AUC 0.687 (95%CI, 0.637-737, sensitivity = 0.620, specificity = 0.668, p < 0.001)). CONCLUSIONS: TyG index can predict the onset of CRC. For early detection of CRC, we should encourage people with high TyG index to undergo screening for CRC.

Impact of metabolically healthy obesity on the risk of incident gastric cancer: a population-based cohort study.

BACKGROUND: The risk of colon or breast cancer in metabolically healthy obese (MHO) were lower than that in metabolically abnormal obese (MAO). We hypothesized that the risk of incident gastric cancer in MHO is lower than that in MAO. METHODS: This historical cohort study included 19,685 Japanese individuals who received health-checkup programs from 2003 to 2016. Each subject was classified as metabolically healthy (MH) (no metabolic abnormalities) or metabolically abnormal (MA) (one or more metabolic abnormalities), according to four metabolic factors (hypertension, impaired fasting glucose, hypertriglyceridemia and low HDL-cholesterol). Obese (O) or non-obese (NO) was classified by a BMI cutoff of 25.0 kg/m2. Hazard ratios of metabolic phenotypes for incident gastric cancer were calculated by the Cox proportional hazard model with adjustments for age, sex, alcohol consumption, smoking and exercise. RESULTS: Over the median follow-up period of 5.5 (2.9-9.4) years, incident rate of gastric cancer was 0.65 per 1000 persons-years. Incident rate of MHNO, MHO, MANO and MAO were 0.33, 0.25, 0.80 and 1.21 per 1000 persons-years, respectively. Compared with MHNO, the adjusted hazard ratios for development of gastric cancer were 0.69 (95% CI 0.04-3.39, p = 0.723) in MHO, 1.16 (95% CI 0.63-2.12, p = 0.636) in MANO and 2.09 (95% CI 1.10-3.97, p = 0.024) in MAO. CONCLUSIONS: This study shows that individuals with MAO, but not those with MHO, had an elevated risk for incident gastric cancer. Thus, we should focus more on the presence of metabolic abnormalities rather than obesity itself for incident gastric cancer.

The Visceral Adiposity Index Is a Predictor of Incident Chronic Kidney Disease: A Population-Based Longitudinal Study.

BACKGROUND AND AIMS: Visceral adiposity index (VAI), calculated with body mass index, high density lipoprotein-cholesterol, triglycerides and waist circumference, has been proposed as a marker of visceral fat accumulation and dysfunction in adipose tissue. METHODS: The impact of VAI on incident chronic kidney disease (CKD) in a historical cohort study of 15,159 (8,260 men and 6,899 women) participants was investigated. CKD was defined when estimated glomerular filtration rate was <60 mL/min/1.73 m2 or proteinuria (positive: ≥1+). We divided the participants into 2 groups according to sex and into quartiles according to VAI (Q1-4). We performed Cox proportional hazard models, adjusting for age, smoking status, exercise, alcohol consumption, systolic blood pressure, hemoglobin A1c, uric acid, and creatinine. RESULTS: During the median 3.3-year follow-up for men and 3.2-year follow-up for women, 1,078 participants (629 men and 449 women) developed CKD. The 4,000 days cumulative incidence rate of CKD for men and women were 3.7 and 3.9% in Q1, 5.2 and 5.9% in Q2, 6.5 and 7.0% in Q3, and 8.4 and 9.3% in Q4 respectively. Compared to Q1, the hazard ratios of incident CKD in Q2, Q3 and Q4 for men and women were 1.23 (95% CI 0.91-1.66, p = 0.184) and 1.30 (0.87-1.96, p = 0.203), 1.42 (1.06-1.90, p = 0.018) and 1.38 (0.94-2.05, p = 0.105), and 1.51 (1.12-2.02, p = 0.006) and 1.65 (1.12-2.46, p = 0.013) respectively. Additionally, the area under the curve of VAI for incidence of CKD was superior to that of VAI in men (0.595 vs. 0.552, p < 0.001) and equal to in women (0.597 vs. 0.591, p = 0.708). CONCLUSIONS: The VAI can be a predictor of incident CKD.

Association between Sleep Duration and Incident Chronic Kidney Disease: A Population-Based Cohort Analysis of the NAGALA Study.

BACKGROUND: The duration of sleep might be a risk factor for chronic kidney disease (CKD). We investigated the relationship between sleep duration and incident CKD. METHODS: In this retrospective cohort study of 7,752 men and 6,722 women, we divided the subjects into 4 groups according to sleep duration, i.e., those whose reported regular sleep duration was <6 h (the "<6 h group"), those whose sleep duration was >6 but <7 h (the "6 to <7 h group"), those with a sleep duration of 7 to <8 h (the "7 to <8 h group"), and those with ≥8 h sleep (the "≥8 h group"). CKD was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The HR of the 4 groups for incident CKD were calculated with a Cox proportional hazards model, with the 7 to <8 h group set as the reference. RESULTS: Incident CKD was detected in 1,513 (19.5%) men and 688 (10.2%) women over the median follow-up period of 7.0 (3.3-11.9) years in the men and 6.7 (3.1-10.8) years in the women. There was no association between sleep duration and incident CKD in the women. In the men, the HR of incident CKD was 0.54 (95% CI 0.45-0.64, p < 0.001) in the <6 h group, 0.73 (95% CI 0.66-0.82, p < 0.001) in the 6 to <7 h group, and 0.93 (95% CI 0.78-1.11, p = 0.433) in the ≥8 h group. CONCLUSION: The risk of incident CKD is lowest in those who sleep <6 h. We revealed that the risk of incident CKD is lowest in those who sleep <6 h among apparently healthy men.

Potential of automatic diagnosis system with linked color imaging for diagnosis of Helicobacter pylori infection.

BACKGROUND AND AIM: It is necessary to establish universal methods for endoscopic diagnosis of Helicobacter pylori (HP) infection, such as computer-aided diagnosis. In the present study, we propose a multistage diagnosis algorithm for HP infection. METHODS: The aims of this study are to: (i) to construct an interpretable automatic diagnostic system using a support vector machine for HP infection; and (ii) to compare the diagnosis capability of our artificial intelligence (AI) system with that of endoscopists. Presence of an HP infection determined through linked color imaging (LCI) was learned through machine learning. Trained classifiers automatically diagnosed HP-positive and -negative patients examined using LCI. We retrospectively analyzed the new images from 105 consecutive patients; 42 were HP positive, 46 were post-eradication, and 17 were uninfected. Five endoscopic images per case taken from different areas were read into the AI system, and used in the HP diagnosis. RESULTS: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis of HP infection using the AI system were 87.6%, 90.4%, 85.7%, 80.9%, and 93.1%, respectively. Accuracy of the AI system was higher than that of an inexperienced doctor, but there was no significant difference between the diagnosis of experienced physicians and the AI system. CONCLUSIONS: The AI system can diagnose an HP infection with significant accuracy. There remains room for improvement, particularly for the diagnosis of post-eradication patients. By learning more images and considering a diagnosis algorithm for post-eradication patients, our new AI system will provide diagnostic support, particularly to inexperienced physicians.

Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study.

OBJECTIVES: Obesity is a risk factor for type 2 diabetes mellitus. Among obesity, visceral fat obesity, and ectopic fat obesity, it has been unclear which has the greatest effect on incident diabetes. METHODS: In this historical cohort study of 8430 men and 7034 women, we investigated the effect of obesity phenotypes on incident diabetes. Obesity, visceral fat obesity, and ectopic fat obesity were defined as body mass index ≥25 kg/m2, waist circumference ≥90 cm in men or ≥80 cm in women, and having fatty liver diagnosed by abdominal ultrasonography, respectively. We divided the participants into eight groups according to the presence or absence of the three obesity phenotypes. RESULTS: During the median 5.8 years follow-up for men and 5.1 years follow-up for women, 286 men and 87 women developed diabetes. Compared to the non-obese group, the hazard ratios (HRs) of incident diabetes in the only-obesity, only-visceral fat obesity, only-ectopic fat obesity groups, and with all-three types of obesity group were 1.85 (95%CI 1.06-3.26, p = 0.05) in men and 1.79 (0.24-13.21, p = 0.60) in women, 3.41 (2.51-4.64, p < 0.001) in men and 2.30 (0.87-6.05, p = 0.12) in women, 4.74 (1.91-11.70, p < 0.001) in men and 13.99 (7.23-27.09, p < 0.001) in women and 10.5 (8.02-13.8, p < 0.001) in men and 30.0 (18.0-50.0, p < 0.001) in women. Moreover, the risk of incident diabetes of the groups with ectopic fat obesity were almost higher than that of the four groups without ectopic fat obesity. CONCLUSION: Ectopic fat obesity presented the greatest risk of incident type 2 diabetes.

Triglyceride-glucose index is a predictor of incident chronic kidney disease: a population-based longitudinal study.

BACKGROUND: Insulin resistance is one of the risks of chronic kidney disease (CKD). The triglyceride-glucose index (TyG index) has been suggested as a marker of moderate insulin resistance. We aimed to investigate the association between TyG index and incident CKD. METHODS: In this historical cohort study of 11,712 participants (6026 men and 5686 women), we investigated the impact of TyG index on incident CKD. CKD was defined as estimated GFR less than 60 mL/min/1.73 m2 and/or proteinuria detected by dipstick test in fasting morning urine. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Cox proportional hazard models were performed to investigate the impact of TyG index on incident CKD, adjusting for age, BMI categories, waist circumference, smoking status, exercise, logarithm of alcohol consumption, systolic blood pressure, serum albumin, hemoglobin A1c, hyperuricemia, low HDL-cholesterol concentration, high LDL-cholesterol concentration, CRP, creatinine, and gamma-glutamyltransferase. RESULTS: During the median 4.0-year follow-up duration for men and 3.7-year follow-up duration for women, 261 participants (120 men and 141 women) developed CKD. In Cox proportional hazard model, TyG index presented the significant risks for incident CKD in both men and women (men, hazard ratio 1.32, 95% confidence interval 1.02-1.70, p = 0.036, women, hazard ratio 1.50, 95% confidence interval 1.05-2.13, p = 0.024). CONCLUSION: This study revealed that TyG index can be a predictor of incident CKD.

Self-reported behavior of eating quickly is correlated with visceral fat area in Japanese non-obese adults.

BACKGROUND AND OBJECTIVES: This cross-sectional study investigated the relationship between eating speed and fat accumulation in Japanese non-obese adults. METHODS AND STUDY DESIGN: In total, 381 non-obese participants aged 35-74 years underwent a health checkup including fat distribution. All participants underwent magnetic resonance imaging to quantify visceral fat area (VFA) and subcutaneous fat area (SFA). Information on eating speed was obtained using a self-administrated questionnaire. RESULTS: The numbers of participants with self-reported behavior of eating slowly, medium, or quickly were 24 (6.3%), 180 (47.2%), and 177 (46.5%), respectively. The prevalence of VFA ≥100 cm2 was higher in the eating quickly group than in the eating slowly (p<0.05) or medium groups (p<0.05). On the other hand, no significant differences in SFA ≥100 cm2 were observed between groups. In addition, multiple stepwise regression analysis showed that eating quickly was positively correlated with VFA (standard ß=0.068, p<0.05), but not with SFA. CONCLUSIONS: Although eating quickly was positively correlated with bigger VFA in Japanese non-obese adults, no associations were found between eating speed and SFA.

Long-Term Effects on Preventing Stroke after Endovascular Treatment or Bypass Surgery for Intracranial Arterial Stenosis.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke worldwide due to its higher risk of recurrence with medical therapy. Although some large randomized studies failed to show the superiority of surgical treatment compared with medical therapy, the results of medical therapy are not sufficient. There are patients who still benefit from surgical treatment. This retrospective analysis aimed to evaluate the long-term efficacy of surgical therapy with percutaneous transluminal angioplasty and/or stenting (PTA/PTAS) or extracranial-intracranial (EC/IC) bypass surgery for patients with ICAS. METHODS: Between October 2005 and December 2016, 55 ICAS patients were treated with PTA/PTAS or EC-IC bypass surgery. Their electronic medical records were retrospectively reviewed and analyzed. The primary outcome was all adverse events beyond 30 days after a revascularization procedure. RESULTS: We performed 21 cases (35%) of PTA, 4 cases (7%) of PTAS, and 34 cases (58%) of EC-IC bypass surgery and the median follow-up duration was 66 months (range 1-144 months). The occurrence rate of the primary outcome was 10.2% and only 1 patient (1.8%) experienced ipsilateral disabling ischemic stroke beyond 30 days. The long-term functional independent survival rate was 83.6%. CONCLUSIONS: We demonstrated a long-term favorable outcome of combined surgical intervention for ICAS patients with PTA/PTAS and EC-IC bypass surgery, and the result was better than previously reported outcomes of medical therapy. Additional multicenter studies are required to draw firm conclusions on the efficacy of reduction of recurrent stroke in patients with ICAS.

Metabolically healthy obesity and risk of leukoaraiosis; a population based cross-sectional study.

Metabolically healthy obese (MHO) individual is known to be defended from the metabolic complications of obesity. Leukoaraiosis, which is commonly detected on brain magnetic resonance imaging (MRI), is now recognized as a risk of stroke, dementia and death. However, the association between MHO and the prevalence of leukoaraiosis is unclear. In this cross-sectional study of 796 participants who received a medical examination program, we investigated the association between MHO and the prevalence of leukoaraiosis. We used common clinical markers for definition of metabolic healthy status: blood pressure, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol concentrations. Obesity was defined by body mass index ≥25.0 kg/m2. We diagnosed leukoaraiosis by fluid-attenuated inversion recovery without hypointensity on T1-weighted images or the presence of a hyperintensity on T2-weighted images. The crude prevalence proportion of leukoaraiosis was 44.5% (case/n = 171/384) in metabolically healthy nonobese (MHNO) individual, 46.3% (44/95) in MHO individual, 62.3% (114/183) in metabolically unhealthy nonobese (MUNO) individual or 56.6% (77/136) in MUO individual. The odds ratios of prevalence of leukoaraiosis were 1.19 (95% CI 0.74-1.90, p = 0.471) for MHO, 1.79 (1.22-2.62, p = 0.003) for MUNO and 1.56 (1.03-2.37, p = 0.037) for MUO individuals after adjusting for sex, age, smoking statues, habit of exercise and alcohol, compared with MHNO individual. We revealed that MHO individuals were not related with the higher risk of leukoaraiosis, whereas MUNO and MUO individuals were.

Nonalcoholic fatty liver disease remission in men through regular exercise.

Recent cross-sectional and randomized controlled studies of small sample sizes revealed that regular exercise is effective for improving nonalcoholic fatty liver disease. However, there has been no large-scale longitudinal study addressing the effect of regular exercise on remission of nonalcoholic fatty liver disease. Thus, we investigated the impact of exercise on the natural history of nonalcoholic fatty liver disease. We analyzed 1,010 (860 men and 150 women) Japanese participants who received health checkups repeatedly over 10 years by a historical cohort study and were diagnosed with nonalcoholic fatty liver disease at baseline. Regular exercise was defined as participating in any kind of sports at least once a week. Nonalcoholic fatty liver disease was diagnosed by ultrasonographic images. During 10 years of follow-up, remission of nonalcoholic fatty liver disease was observed in 46.0% (396/860) of men and 48.7% (73/150) of women. In men, the adjusted hazard ratio of regular exercise for remission of nonalcoholic fatty liver disease was 1.46 (95% confidence interval 1.10-1.95, p = 0.010). However, this was not significant in women. Exercise at least once a week is implicated in the remission of nonalcoholic fatty liver disease in men.

Impact of fatty liver disease and metabolic syndrome on incident type 2 diabetes; a population based cohort study.

Fatty liver disease and metabolic syndrome (MetS) are both shown to increase the risk of type 2 diabetes. The aim of this study was to investigate the combined effect of fatty liver and MetS on incident diabetes. In this cohort study of 17,810 participants, fatty liver was diagnosed by abdominal ultrasonography and MetS was defined by a joint interim statement. We divided the participants into four groups according to the presence of fatty liver and/or MetS. Type 2 diabetes was defined as HbA1c ≥6.5%, fasting plasma glucose ≥7.0 mmol/L or treatment for diabetes. During the follow up examination (median 5.1 years), 804 participants developed diabetes. Compared with non-MetS without fatty liver, hazard ratios (HR) for incident diabetes after adjusting for age, body mass index, smoking status, exercise habit, alcohol consumption, family history of diabetes logarithm of alanine aminotransferase and fasting plasma glucose, were as follow: 2.35 (95 % CI 1.91-2.89, p<0.001) in non-MetS with fatty liver, 1.70 (95% CI 1.30-2.20, p<0.001) in MetS without fatty liver, and 2.33 (95% CI 1.85-2.94, p<0.001) in MetS with fatty liver. In addition, adjusted HRs for incident diabetes compared with MetS without fatty liver were 1.39 (95% CI 1.07-1.80, p=0.012) in non-MetS with fatty liver and 1.38 (95% CI 1.07-1.79, p=0.013) in MetS with fatty liver. Fatty liver affects more on the risk of incident diabetes than MetS. To prevent the further risk of diabetes, we should pay more attention to fatty liver.

The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals.

BACKGROUND & AIMS: The aim of this study was to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on incident type 2 diabetes mellitus (T2DM) in non-overweight individuals with NAFLD. METHODS: A population-based retrospective cohort study of 4629 participants who were enrolled in a health check-up programme for more than 10 years. A standardized questionnaire and abdominal ultrasonography were used to diagnose NAFLD. A cut-off point of BMI 23 kg/m(2) was used to define overweight (≥23.0 kg/m(2)) or non-overweight (<23.0 kg/m(2)). The primary outcome was incident T2DM. RESULTS: Over a mean follow-up of 12.8 years, 351 participants (7.6%) developed T2DM. The incidence rate of T2DM was 3.2% in the non-overweight without NAFLD group, 14.4% in the non-overweight with NAFLD group, 8.0% in the overweight without NAFLD group and 26.4% in the overweight with NAFLD group. The adjusted hazard ratios for incident T2DM compared with the non-overweight without NAFLD group were as follows: 3.59 (95% CI: 2.14-5.76) in the non-overweight with NAFLD group, 1.99 (95% CI: 1.47-2.69) in the overweight without NAFLD group and 6.77 (95% CI: 5.17-8.91) in the overweight with NAFLD group. The adjusted hazard ratio in the non-overweight with NAFLD group was significantly higher than that in the overweight without NAFLD group or that in the non-overweight without NAFLD group. CONCLUSIONS: Non-overweight individuals with NAFLD had a high risk of incident T2DM. Diagnosis of NAFLD is important in non-overweight individuals, and therefore it might be necessary to follow their health conditions on a long-term basis after detection of NAFLD.