Intracholecystic papillary neoplasm (ICPN) is a rare premalignant lesion of the gallbladder, and its natural history remains incompletely understood. We report a case of ICPN presenting as a small gallbladder polyp with progressive growth. A 56-year-old woman was found to have a gallbladder polyp measuring 7.6 mm, which increased to 11.2 mm over 2 years and 8 months. Contrast-enhanced computed tomography demonstrated a papillary lesion with enhancement. Laparoscopic cholecystectomy was performed. Histopathological examination revealed pyloric gland-type ICPN with low-grade dysplasia without invasive carcinoma. Immunohistochemical analysis showed positivity for MUC6 and MUC5AC, supporting gastric-type differentiation. No recurrence has been observed during postoperative follow-up. This case suggests that progressive growth, papillary morphology, and enhancement characteristics may indicate neoplastic potential even in gallbladder polyps initially measuring < 10 mm, suggesting the importance of careful follow-up and timely surgical intervention.

This study aimed to clarify the relationship between periodontitis and non-alcoholic fatty liver disease (NAFLD). A survey was conducted with 2,453 participants who visited the dental clinic at the Asahi University Hospital. Periodontitis was evaluated using the Community Periodontal Index (CPI), and NAFLD was evaluated using multiple tools such as Fibrosis-4 (FIB4), NAFLD fibrosis score (NFS), and Fatty Liver Index (FLI). The relationship between periodontitis and the cutoff values of three NAFLD assessment tools by logistic regression analyses indicated that PPD ≥ 6 mm was significantly associated with NFS > 0.675 (OR = 4.11, 95%CI:1.06–15.99) and with FLI ≥ 60 (OR = 1.76, 95%CI:1.12–2.76). The participants with BOP positive indicated a significant association between PPD ≥ 6 mm and FLI ≥ 60 (OR = 1.68, 95%CI:1.05–2.70). However, no association was found in participants without BOP. These results suggest that periodontal inflammation is associated with NAFLD, as assessed using the FLI.

Abstract Background Although mismatch repair–deficient (dMMR)/microsatellite and instability–high (MSI-H) status is recognized as a biomarker that predicts the efficiency of immune checkpoint inhibitors (ICIs), the efficacy of ICIs treatment is still insufficient. Accordingly, insights into the mechanisms of acquired resistance to ICIs in gastrointestinal cancers are necessary, and developing immunotherapeutic strategies to improve response rates is an urgent clinical priority. We investigated the clinical characteristics of dMMR/MSI-H early gastric cancer and analyzed the expression patterns of immune checkpoint molecules within the tumor microenvironment. Method A total of 20 cases of early gastric cancer, treated between November 2019 and July 2024, were included. Immunohistochemistry was performed to assess the expression of mismatch repair (MMR) protein, and patient clinical characteristics were evaluated. Additionally, among the eight cases identified as dMMR early gastric cancer, they were further examined for the expression of immune checkpoint molecules in the tumor microenvironment using immunohistochemical staining. Result The median age of patients diagnosed with dMMR early gastric cancer was 73 years. In 20 patients, female sex and severe atrophy were associated with dMMR status in univariate analysis (OR 7.67, 95% CI 1.04–94.53). The expression pattern of immune checkpoint molecules showed heterogeneity. Conclusion These findings highlight the heterogeneity of immune checkpoint expression patterns and provide preliminary, hypothesis-generating insights into variability in response to PD-1/PD-L1 blockade.

A body shape index (ABSI), calculated using height, weight, and abdominal circumference, has attracted attention as a new indicator of obesity that is independent of the body mass index (BMI). This cross-sectional study investigated whether ABSI was associated with periodontal disease in 3,797 participants who visited Asahi University Hospital. The modified community periodontal index was used to evaluate presence of periodontal disease. Participants with BMI ≥ 25 kg/m2 or ABSI ≥ 0.0080 were defined as obese. Overall, the present study included 2476 participants (65

BACKGROUND AND AIMS:Steatotic liver disease (SLD) affects more than 30% of the global population; however, trends in its prevalence remain poorly understood. This study aimed to elucidate prevalence trends of metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with moderate alcohol intake (MetALD), and alcohol-associated liver disease (ALD) in the Japanese general population. METHODS:This retrospective study included participants who underwent health checkups between 2004 and 2022 in Gifu, Japan. SLD was defined by liver ultrasonography and categorised as either MASLD, MetALD, or ALD in the total population, as well as in non-obese (body mass index [BMI] ≤ 25 kg/m2), and lean (BMI ≤ 23 kg/m2) subgroups. Annual percent change (APC) in the prevalence of each SLD subtype was analysed using the Joinpoint regression model. RESULTS:Among 184 463 participants, 49 651 (26.9%) were diagnosed with SLD, including 41 819 (22.7%) with MASLD, 3792 (2.1%) with MetALD, and 2037 (1.1%) with ALD. Over the study period, APC in the total population revealed significant increases in MASLD (APC, 2.02%; 95% confidence interval [CI], 1.46-2.66; p < 0.001) and MetALD (APC, 1.14%; 95% CI, 0.17-2.19; p = 0.026), with similar trends observed in the non-obese and lean subgroups. ALD prevalence increased only in the lean population (APC, 2.87%; 95% CI, 0.33-5.94; p = 0.031). CONCLUSIONS:MASLD and MetALD increased significantly irrespective of body composition, whereas ALD increased in the lean population over the past two decades. These findings highlight a silent rise of SLD in the Japanese general population.

BackgroundA decade-long follow-up study identified metabolic dysfunction-associated fatty liver disease (MAFLD) as an independent predictor for the onset of chronic kidney disease (CKD). In 2023, a Delphi consensus introduced the term metabolic dysfunction-associated steatotic liver disease (MASLD) as an updated nomenclature. This study aims to evaluate whether MASLD, as the newly defined concept of steatotic liver disease, functions as an independent risk factor for CKD development. Additionally, the study seeks to examine the association between MASLD and CKD, while identifying contributing risk factors.MethodsThis research involved a retrospective cohort study conducted on individuals participating in health checkups at Asahi University Hospital, Japan, from 1994 to 2023. Logistic regression analysis was employed to investigate the relationship between MASLD and the incidence of CKD over a five-year follow-up period.ResultsA total of 15,873 participants were included in this study. The incidence of CKD was highest among individuals with MASLD (9.5%). Multivariate analysis demonstrated that MASLD was significantly associated with an increased risk of CKD, with an odds ratio (OR) of 1.37 (95% CI 1.12-1.67, p = 0.002). Additional factors such as age (OR 1.04, 95% CI 1.03-1.05, p < 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.88, 95% CI 0.87-0.89, p < 0.001) were also identified as significant predictors of CKD. These findings suggest a robust association between MASLD and an elevated risk of CKD compared to individuals without steatotic liver disease or cardiometabolic risk factors.ConclusionsThis study establishes MASLD as a significant risk factor for CKD onset. Effective identification and management of MASLD cases are essential to mitigate the incidence of CKD.

AIMS:In Japan, several prediction models and scoring systems for type 2 diabetes have been reported; however, none have high utility. We developed a new clinical prediction model for the onset of type 2 diabetes. MATERIALS AND METHODS:The development dataset was obtained from 72,124 Japanese employees who participated in a health check-up programme conducted by Panasonic Corporation (Osaka, Japan), were aged 40 years or older, were diabetes-free at baseline, and followed-up for up to 10 years. The external validation dataset was obtained from 12,885 participants of the NAGALA (Gifu City, Gifu Prefecture Longitudinal Analysis) cohort. A prediction model was developed to predict the 10-year risk of developing diabetes using information from the health checkup programme. The developed model was internally validated, and externally validated using the NAGALA cohort. RESULTS:Using information on age, sex, body mass index, systolic blood pressure, log-triglycerides, high-density lipoprotein, log-alanine aminotransferase, fasting plasma glucose, weight gain, and smoking status obtained from a health checkup programme, we developed a novel, highly sensitive, and specific model for predicting the 10-year risk of developing diabetes. The prediction model showed excellent performance, with an optimism-corrected c-index of 0.877 and a c-index of 0.882 in the external validation cohort. CONCLUSION:We developed a noninvasive diabetes risk-prediction model for the Japanese population and confirmed its utility for identifying individuals at high risk of type 2 diabetes over time.

Objectives: There is a relationship between insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) and the estimated glucose disposal rate (eGDR), which has been reported as a surrogate marker of insulin resistance. This study aimed to investigate the association between eGDR and the incident MASLD, and compare the ability to predict incident MASLD with other insulin resistance markers. Methods: Retrospective cohort data from a health check-up program were analyzed. Participants were categorized into 4 subgroups according to eGDR quartiles. To assess the association between eGDR quartiles and incident MASLD, logistic regression analyses were used. Additionally, to compare the predictive ability of eGDR, triglyceride/high-density lipoprotein (HDL) cholesterol (TG/HDL) ratio, and triglyceride glucose index with respect to incident MASLD, receiver operating characteristics analysis was used. Results: Of 16 689 participants were included, 3654 developed MASLD. After multivariate adjustment, compared with the lowest eGDR quartile, odds ratios (95% confidence interval [CI]) for incident MASLD in the second, third, and highest GDR quartiles, were 0.775 (0.692-0.868), 0.478 (0.4080.560), and 0.147 (0.110-0194), respectively. The association between lower eGDR levels and MASLD risk remained consistent across stratification by sex and obesity status. Moreover, the area under the receiver operating characteristics curve (95% CI) for eGDR (0.8 [0.79-0.81]) was higher than for TG/ HDL ratio 0.76 [0.79-0.81]) and triglyceride glucose index (0.75 [0.74-0.76]). Conclusions: Lower eGDR levels were associated with an increased risk of incident MASLD. Our findings suggest that eGDR may be a more effective tool for predicting MASLD risk. (c) 2025 Published by Elsevier Inc. on behalf of the AACE.

Waist circumference (WC) and body mass index (BMI) are considered useful for the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate the association between the body roundness index (BRI) and a body shape index (ABSI) with incident MASLD, in comparison to WC and BMI. Retrospective cohort data from a Japanese health check-up program were analyzed. Logistic regression model was used to evaluate the associations between anthropometric measure quartiles and MASLD, and receiver operating characteristic (ROC) analysis was performed to evaluate the associations between anthropometric measures and incident MASLD, stratified by sex. A total of 10,561 males and 7,187 females were included, of whom 3,182 males and 914 females developed MASLD. Multivariate analysis revealed that higher WC, BMI, and BRI were associated with incident MASLD in both sexes, whereas higher ABSI was significantly associated with incident MASLD only in females. Among males, the area under the ROC curve (AUC) of BMI was higher than that of WC, BRI, and ABSI. Conversely, among females, the AUC of BMI was higher than that of ABSI, whereas it was comparable to that of WC or BRI. The AUC and the optimal cut-off values of BMI for predicting incident MASLD were 0.77 and 23.9 kg/m2 in males, and 0.86 and 22.2 kg/m2 in females. The optimal cut-off values of WC were 82.0 cm for males and 76.3 cm for females, respectively. We demonstrated the strongest association between BMI and incident MASLD compared to other measures, particularly in males, while also showing a strong association in females. Additionally, specific WC criteria for Asians to improve MASLD diagnosis are needed.

ABSTRACT Aims/Introduction The 2023 Delphi consensus recommended the use of new term, metabolic dysfunction‐associated steatotic liver disease (MASLD), aiming conceptual shift from the conventional non‐alcoholic fatty liver disease (NAFLD). The association between NAFLD and type 2 diabetes mellitus (T2DM) development is well known. This study aimed to examine the correlation between MASLD and T2DM development, comparing their utility as predictors. Materials and Methods This retrospective cohort study obtained data from a medical health checkup program conducted at Asahi University Hospital, Japan, between 2004 and 2021. Logistic regression analysis was used to assess the association between MASLD and incident T2DM over 5 years. To compare the predictive utility of NAFLD and MASLD, receiver operating characteristic curves were drawn, followed by area under the curve (AUC) comparisons. Results In total, 15,039 participants (59.6% males; median [interquartile range {IQR}] age, 44 [38, 50] years) were included. Out of 2,682 participants meeting the criteria for MASLD, 234 individuals (8.7%) developed T2DM. Multivariate analysis revealed a significantly elevated risk of T2DM in MASLD compared with the reference healthy group (without steatotic liver disease or cardiometabolic risk), presenting an OR of 127.00 (95% CI 40.40–399.00, P < 0.001). The concordance rate of diagnosis between NAFLD and MASLD was 98.7%. The AUC values were 0.799 for NAFLD and 0.807 for MASLD, respectively. Comparative analysis of the AUC showed a statistical difference between NAFLD and MASLD (P < 0.001). Conclusions MASLD was shown to be a significant risk factor for incident T2DM, exhibiting a potentially higher predictive capacity than conventional NAFLD.

INTRODUCTION:Vonoprazan has been known to have a high Helicobacter pylori (H. pylori) eradication rate since its launch in 2015. Yet, the risk factors for eradication failure and development of post-eradication gastric cancer (GC) using VPZ regimen remain unclear. METHODS:This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using VPZ between February 2015 and June 2017 and were followed up for five years by the end of 2022. We examined several indicators of systemic immune, inflammatory, and nutritional status at the time of eradication to identify those indicators could predict eradication success, risk of post-eradication GC development, and long-term prognosis. RESULTS:The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Multivariate analysis showed that only a high peripheral blood neutrophil-to-lymphocyte ratio (NLR) was significantly associated with eradication failure. The 5-year GC incidence rate was 1.67%, and all GCs were stage IA. The mean (standard deviation [SD]) time from eradication to diagnosis was 40.5 (6.1) months. Multivariate analysis showed that high NLR and history of GC and hypertension were significantly associated with GC development. Patients with elevated NLR post-eradication had a higher risk of newly developed GC. Twelve patients died during the study period, and a high NLR was associated with a significantly higher mortality rate. CONCLUSIONS:NLR has the potential to be a biomarker that predicts the failure of eradication and development of post-eradication GC. High NLR was also associated with poor long-term prognosis after H. pylori eradication.

Early detection of gastric cancer can play a key role in improving prognosis. Recently, light-emitting diodes (LED) have been developed as novel endoscopic systems. However, the differences in the visibility of gastric neoplastic lesions between LED and laser endoscopy remains unclear. We conducted a prospective multicenter trial to evaluate the non-inferiority of LED endoscopy in the visibility of gastric neoplastic lesions undergoing endoscopic submucosal dissection (ESD) in comparison to laser endoscopy. A multicenter, prospective, cross-sectional study was conducted in patients undergoing ESD for gastric neoplastic lesions at five hospitals throughout Japan. Seventy patients with 74 lesions were included in this study. The primary endpoint was the non-inferiority of the difference in the individual scores of linked color imaging (LCI) and white-light imaging (WLI) for LED and laser endoscopy for gastric neoplastic lesions. The mean individual score was 2.66 ± 1.02, 3.17 ± 0.83, 2.75 ± 1.05, and 3.21 ± 0.84 in LED-WLI, LED-LCI, laser-WLI, and laser-LCI, respectively. The difference in individual scores of LCI and WLI was 0.51 ± 0.77 and 0.46 ± 0.80 in LED and laser endoscopy, respectively. The mean difference between LED and laser endoscopy was 0.04 (95

Background: This study aimed to investigate the relationship between an increase in waist circumference (WC) after 1 year and self-reported chewing status in 10,870 Japanese adults who had received health checkups. Subsequently, 8068 participants were included in the final analysis. Methods: We defined an increase in WC ≥ 5 cm after 1 year as an unhealthy increase; in total, 613 (7.5%) respondents met this criterion. Chewing status was evaluated using a self-reported questionnaire at baseline; 1080 (13%) respondents were diagnosed with poor chewing status. Results: After adjusting for age, gender, WC, body mass index (BMI), and chewing status, an increase in WC ≥ 5 cm was found to be positively associated with gender (females: odds ratios [ORs]: 1.206; 95% confidence intervals [CIs]: 1.008–1.443), WC (ORs: 0.967; 95% CIs: 0.954–0.981), BMI (≥25 kg/m2; ORs: 2.194; 95% CIs: 1.715–2.808), and chewing status (poor; ORs: 1.356; 95% CIs: 1.084–1.697). Conclusions: These findings suggest that increased WC after 1 year was associated with self-reported poor chewing status in Japanese adults.

Background While many studies indicate a negative correlation between high-density lipoprotein cholesterol (HDL-C) and the occurrence of diabetes, there are still some inconsistent findings. The contentious relationship between the two may be partially due to the undistingushement between the pre-diabetic and the normoglycemic participants in the previous studies, which may confound the association. This study aimed to investigate the relationship between the baseline HDL-C and incident type 2 diabetes mellitus (T2DM) in a Japanese cohort with normoglycemia or with prediabetes, respectively. Method In total, 10120 men (6791 with normoglycemia and 3329 with prediabetes) were enrolled from the NAGALA cohort from Jan 5th, 2004 to Dec 26th, 2015. Cox proportional hazards models were conducted to explore the association between baseline HDL-C levels and incident T2DM. A two-piecewise linear regression model was performed to evaluate the threshold effect of the baseline HDL-C concentration on T2DM incidence by using a smoothing function. Results During the median 5.95-year follow-up duration for participants with normoglycemia and 4.33-year follow-up period for prediabetes, 88 participantes with normoglycemia and 494 participantes with prediabetes developed T2DM. In the crude model and partly adjusted model, the risk of T2DM decreased significantly in both normoglycemia and prediabetes with increment in baseline HDL-C concentration. Howerver, the associations became nonsignificant after fully adjusting for possible confounders. Interestingly, in prediabetes, an L-shaped relationship between baseline HDL-C and risk of incident T2DM with a threshold HDL-C concentration of 32.4mg/dl was determined: the T2DM risk sharply decreased by 62% with the each 10mg/dl increment in HDL-C levels (HR = 0.377, 95%CI = 0.191–0.743) and the decline reaches a near plateau when the HDL-C concentration is higher than 32.4 mg/dl (HR = 0.986, 95%CI = 0.895–1.085). Conclusions Among a Japanese male population, an L-shape relationship between baseline HDL-C concentration and the risk of incident T2DM was explored in prediabetes, while no significant association was detected in men with normoglycemia.

AimMetabolic 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.MethodsThis 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.ResultsAfter 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.ConclusionsAmong 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. Patients with non-alcoholic fatty liver disease could achieve remission with weight loss, although the link between weight loss and metabolic dysfunction-associated fatty liver disease (MAFLD) remission is unclear. Our study shows that weight loss is associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The cutoff values for MAFLD remission were a loss of 1.9 kg, 3.0 kg, 1.9 kg, and 0.8 kg for all participants, participants with type diabetes, overweight participants, and non-overweight patients with metabolic dysfunctions, respectively.image

Background: This longitudinal study aimed to investigate the relationship between self-reported chewing status and increases in waist circumference (WC) after 1 year in 10,870 Japanese adults who had received health checkups. Subsequently, 8,068 participants were included in the final analysis at follow-up. Methods: Chewing status was evaluated using a self-reported questionnaire at baseline; 1,080 (13%) respondents were diagnosed as having poor chewing status. We defined an increase in WC of ≥ 5 cm after 1 year as an unhealthy increase; in total, 613 (7.5%) respondents met this criterion. Results: After adjusting for age, gender, WC, body mass index (BMI), and chewing status, an increase in WC ≥ 5 cm was found to be positively associated with gender (females: odds ratios [ORs]: 1.206; 95% confidence intervals [CIs]: 1.008–1.443), WC (ORs: 0.967; 95% CIs: 0.954–0.981), BMI (≥ 25 kg/m2; ORs: 2.194; 95% CIs: 1.715–2.808), and chewing status (poor; ORs: 1.356; 95% CIs: 1.084–1.697). Conclusions: These findings suggest that self-reported poor chewing status is associated with increases in WC after 1 year in Japanese adults.

Zinc is an essential element and important for inflammatory bowel disease patients. Herein, we aimed to elucidate the correlation between serum zinc concentration and various parameters, especially the disease activity index and endoscopic scores, in these patients. We measured serum zinc concentrations in 37 patients with Crohn's disease and 64 with ulcerative colitis and retrospectively analyzed patient characteristics, blood test values, disease activity, and endoscopic scores. Hypozincemia (<80 ‍μg/dl) was observed in 45.9% and 29.7% of patients with Crohn's disease and ulcerative colitis, respectively. Serum zinc concentration showed a weak negative correlation with Crohn's Disease Activity Index and C-reactive protein levels in Crohn's disease patients, and a weak negative correlation with white blood cell count in ulcerative colitis patients. The zinc concentrations in ulcerative colitis patients were significantly lower in Mayo endoscopic sub-score grade 2 than in grades 0 and 1. The simple endoscopic score for Crohn's disease moderately correlated with zinc concentration. In addition, serum zinc concentration showed a moderate correlation with serum albumin and Onodera's prognostic nutritional index in both Crohn's disease and ulcerative colitis patients. Serum zinc concentration clearly correlated with inflammatory bowel disease activity, endoscopy scores, and immunonutritional parameters, suggesting the importance of monitoring zinc levels.

Helicobacter pylori (H. pylori) infection is a cause of gastric disorders and is treated mainly by pharmacotherapy with antimicrobial agents. An association has been reported between dental caries and H. pylori infection. As antimicrobial agents are less effective inside dental caries because of impaired blood circulation, the presence of untreated dental caries (decayed teeth) may influence the success of H. pylori eradication treatment. In this cross-sectional study, we examined whether failed eradication of H. pylori was associated with decayed teeth in Japanese adults. Enrolled were 226 participants who received dental checkups among those treated for eradication of H. pylori at Asahi University Hospital between April 2019 and March 2021. Treatment efficacy was assessed by urea breath test. Eradication failed in 38 participants (17%), decayed teeth in 32 participants (14%), and number of 0.34 teeth per participants. Multivariate logistic regression analyses showed that failed eradication of H. pylori was associated with decayed teeth (presence: odds ratio, 2.672; 95% confidence interval, 1.093-6.531) after adjusting for gender, age, and brushing frequency. These results indicate that failed eradication of H. pylori was associated with decayed teeth and suggest that untreated dental caries may impact treatment for eradication of H. pylori.

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.