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ObjectivesObesity 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.MethodsIn 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.ResultsDuring 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.ConclusionEctopic fat obesity presented the greatest risk of incident type 2 diabetes.

Microplastics (MPs) are small particles of plastic ( in diameter). In recent years, oral exposure to MPs in living organisms has been a cause of concern. Leaky gut syndrome (LGS), associated with a high-fat diet (HFD) in mice, can increase the entry of foreign substances into the body through the intestinal mucosa. We aimed to evaluate the pathophysiology of intestinal outcomes associated with consuming a high-fat diet and simultaneous intake of MPs, focusing on endocrine and metabolic systems. C57BL6/J mice were fed a normal diet (ND) or HFD with or without polystyrene MP for 4 wk to investigate differences in glucose tolerance, intestinal permeability, gut microbiota, as well as metabolites in serum, feces, and liver. In comparison with HFD mice, mice fed the HFD with MPs had higher blood glucose, serum lipid concentrations, and nonalcoholic fatty liver disease (NAFLD) activity scores. Permeability and goblet cell count of the small intestine (SI) in HFD-fed mice were higher and lower, respectively, than in ND-fed mice. There was no obvious difference in the number of inflammatory cells in the SI lamina propria between mice fed the ND and mice fed the ND with MP, but there were more inflammatory cells and fewer anti-inflammatory cells in mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. The expression of genes related to inflammation, long-chain fatty acid transporter, and cotransporter was significantly higher in mice fed the HFD with MPs than in mice fed the HFD without MPs. Furthermore, the genus was significantly more abundant in the intestines of mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. gene expression was decreased when palmitic acid and microplastics were added to the murine intestinal epithelial cell line MODE-K cells, and Muc2 gene expression was increased when IL-22 was added. Our findings suggest that in this study, MP induced metabolic disturbances, such as diabetes and NAFLD, only in mice fed a high-fat diet. These findings suggest that LGS might have been triggered by HFD, causing MPs to be deposited in the intestinal mucosa, resulting in inflammation of the intestinal mucosal intrinsic layer and thereby altering nutrient absorption. These results highlight the need for reducing oral exposure to MPs through remedial environmental measures to improve metabolic disturbance under high-fat diet conditions. https://doi.org/10.1289/EHP11072.

BackgroundInsulin 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.MethodsIn 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.ResultsDuring 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).ConclusionThis study revealed that TyG index can be a predictor of incident CKD.

A 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. This 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. A 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. This 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.

Background and Aims To clarify the relationship between metabolic dysfunction‐associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Methods The participants were divided into four groups by the presence or absence of fatty liver disease (FLD) and metabolic dysfunction (MD). MAFLD was defined as having both FLD and MD, whereas CKD was defined as having an estimated glomerular filtration rate of <60 mL/min/1.73 m2 and/or proteinuria. Results In this cross‐sectional study of 27,371 participants, the proportions of those in the non‐FLD without MD, non‐FLD with MD, FLD without MD, and MAFLD groups were 48.7, 28.2, 2.3, and 20.8%, respectively. Compared with non‐FLD without MD, MAFLD was associated with the risk of CKD (adjusted odds ratio 1.83 [1.66–2.01], P < 0.001), whereas FLD without MD was not (1.02 [0.79–1.33], P = 0.868). Moreover, compared with FLD without MD, MAFLD was associated with the risk of CKD (1.19 [1.09–1.31], P < 0.001). In this retrospective cohort study, 16,938 of 27,371 participants underwent a median 4.6 (2.0–8.1) years follow‐up, and incident data of non‐FLD without MD, non‐FLD with MD, FLD without MD, and MAFLD were 21.0, 31.1, 26.1, and 31.1 cases per 1,000 person‐years, respectively. Compared with the non‐FLD without MD, MAFLD was associated with the risk of incident CKD (adjusted hazard ratio 1.24 [1.14–1.36], P < 0.001), whereas FLD without MD was not (1.11 [0.85–1.41], P = 0.433). Conclusions MAFLD was associated with a risk of CKD, whereas FLD without MD was not a risk for CKD. Metabolic associated fatty liver disease (MAFLD) was associated with the risk of chronic kidney disease (CKD). Fatty liver without metabolic dysfunction was not associated with the risk of CKD. MAFLD is an important treatment target for extra‐hepatic disease.

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.

The importance of maintaining the remission of nonalcoholic fatty liver disease (NAFLD) has been overlooked. Here we aimed to clarify factors causing NAFLD recurrence. In this retrospective cohort study over 10.8 ± 5.4 years, we investigated 1260 male health check-up participants diagnosed with NAFLD who achieved remission. The data were compared between the maintained remission and recurrence group. Among all participants, 618 (49.0%) showed NAFLD recurrence at the last visit. Participants in the maintained remission group continued to lose weight (72.7 ± 9.1, 68.7 ± 8.5 and 68.2 ± 8.9 kg), whereas those in the recurrence group lost and regained weight (72.9 ± 9.9, 69.7 ± 9.3 and 73.0 ± 10.4 kg). Receiver operating characteristic curve analysis showed a weight regain of + 1.5 kg as the cutoff value for recurrence. The proportion of regular exercisers at the last visit was 34.6% in the maintained remission group and 24.5% in the recurrence group ( p  < 0.0001). Multivariable analysis revealed the amount of weight regain (in 1 kg increments; adjusted odds ratio, 1.29; 95% confidence interval, 1.24–1.34) and regular exercise at the last visit (adjusted odds ratio, 0.67; 95% confidence interval, 0.55–0.89) were independently associated with recurrence. These findings demonstrate a weight regain of 1.5 kg or more and lack of exercise were associated with NAFLD recurrence.

Oral exposure to microplastics (MPs) is a global health concern. In our previous study, MPs induced glucose intolerance and non-alcoholic fatty liver disease (NAFLD) under a high-fat diet-induced leaky gut syndrome (LGS). This study aims to evaluate the effects of high concentrations of MP on lipid metabolism under normal dietary conditions and to assess the changes in the intestinal tract resulting from MP exposure. C57BL6/J mice were fed a normal diet (ND) without polystyrene MPs (PS-MPs) or with PS-MPs (1000 µg/L or 5000 µg/L) for six weeks. Subsequently, intestinal permeability, gut microbiota, and metabolite levels in the serum, feces, and liver were determined. Mice fed the ND showed no increase in intestinal permeability in either group. However, high MPs concentrations led to increased serum lipid levels and exacerbated fatty liver function. Oral exposure to MPs did not affect the number of innate lymphoid cells or short-chain fatty acids in the intestine. However, it increased the number of natural killer cells, altered the gut microbiota, induced inflammation, and modulated the expression of genes related to nutrient transport in the intestine. The severity of intestinal disturbance tended to worsen with dose. Despite the absence of LGS, high concentrations of MPs induced dyslipidemia and NAFLD. Oral exposure to MPs triggered intestinal inflammation via natural killer cells, altered the gut microbiota, and modulated nutrient metabolism. Our study highlights the need for environmental measures to reduce oral MPs exposure in the future.

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. MASLD was a stronger predictor of type 2 diabetes compared with NAFLD, with a significantly higher risk observed in individuals with MASLD.

Many nutritional and epidemiological studies have shown that high consumption of trans fatty acids can cause several adverse effects on human health, including cardiovascular disease, diabetes, and cancer. In the present study, we investigated the effect of trans fatty acids on innate immunity in the gut by observing mice fed with a diet high in trans fatty acids, which have been reported to cause dysbiosis. We used C57BL6/J mice and fed them with normal diet (ND) or high-fat, high-sucrose diet (HFHSD) or high-trans fatty acid, high-sucrose diet (HTHSD) for 12 weeks. 16S rRNA gene sequencing was performed on the mice stool samples, in addition to flow cytometry, real-time PCR, and lipidomics analysis of the mice serum and liver samples. RAW264.7 cells were used for the studies. Mice fed with HTHSD displayed significantly higher blood glucose levels and advanced fatty liver and intestinal inflammation, as compared to mice fed with HFHSD. Furthermore, compared to mice fed with HFHSD, mice fed with HTHSD displayed a significant elevation in the expression of CD36 in the small intestine, along with a reduction in the expression of IL-22. Furthermore, there was a significant increase in the populations of ILC1s and T-bet-positive ILC3s in the lamina propria in mice fed with HTHSD. Finally, the relative abundance of the family , which belongs to the phylum , was significantly higher in mice fed with HFHSD or HTHSD, than in mice fed with ND; between the HFHSD and HTHSD groups, the abundance was slightly higher in the HTHSD group. This study revealed that compared to saturated fatty acid intake, trans fatty acid intake significantly exacerbated metabolic diseases such as diabetes and fatty liver.