Leisure-Time Physical Activity in Subjects with Metabolic-Dysfunction-Associated Steatotic Liver Disease: An All-Cause Mortality Study.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects 30% of adults worldwide and is associated with obesity and cardiovascular risk factors. If left untreated, it can progress to severe liver disease. Lifestyle changes such as physical activity and weight loss help to reduce the severity and risk of mortality. This study estimated the impact of MASLD and leisure-time physical activity (LTPA) on mortality and examined how gender mediates this effect in a Southern Italian population. Methods: This work is a population-based prospective cohort study of inhabitants of Castellana Grotte (>30 years old) in Southern Italy, which began in 1985. Participants provided general health information, underwent anthropometric measurements and ultrasonography, and completed a validated questionnaire on their food intake and LTPA. The vital status was tracked through local municipalities Results: In total, 1826 participants (39% with MASLD) were enrolled in this study, drawn from 2970 eligible subjects; the mean age was 51.91 (±14.76) years and 56.2% were men. Subjects with MASLD who practiced low LTPA had a significantly higher risk of death than those who did not have MASLD and practiced high LTPA. In addition, subjects with MASLD who practiced low LTPA were about 19% less likely to survive to the age of 82 years. As regards gender, both men and women with MASLD and low LTPA showed a significant risk of death, but this was higher in women. Conclusions: The presence of MASLD, especially in women, increases the risk of death from all causes. LTPA plays a key role in the disease and reduces mortality in these individuals.

Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity. OBJECTIVE: The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy. DESIGN: The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study. PARTICIPANTS: A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study. EXPOSURES: Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years. MAIN MEASURES: The association of exposures with the probability of belonging to a certain NAFLD degree of severity. KEY RESULTS: The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting. CONCLUSIONS: The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old.

Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Development and Internal Validation of a Model for Predicting Overall Survival in Subjects with MAFLD: A Cohort Study.

Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R2D 0.6845 and Harrell's C 0.8422 in the development and R2D 0.6930 and Harrell's C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed ß were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol -0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP -0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities.

Enhanced Physical Capacity and Gastrointestinal Symptom Improvement in Southern Italian IBS Patients following Three Months of Moderate Aerobic Exercise.

Moderate-intensity aerobic exercise improves gastrointestinal (GI) health and alleviates irritable bowel syndrome (IBS) symptoms. This study explored its effects on physical capacity (PC) and IBS symptoms in 40 patients from Southern Italy (11 males, 29 females; 52.10 ± 7.72 years). The exercise program involved moderate-intensity aerobic exercise (60/75% of HRmax) for at least 180 min per week. Before and after the intervention, participants completed the IBS-SSS questionnaire to assess IBS symptoms, reported their physical activity levels, and underwent field tests to evaluate PC. PC was quantified as the Global Physical Capacity Score (GPCS). A total of 38 subjects (21 males, 17 females; 53.71 ± 7.27 years) without lower GI symptoms served as a No IBS group. No significant differences were found between IBS patients and No IBS subjects, except for the symptom score, as expected. After the exercise, all participants experienced significant improvements in both IBS symptoms and PC. Higher PC levels correlated with greater benefits in IBS symptomatology, especially with GPCS reaching above-average values. Engaging in moderate-intensity aerobic exercise for at least 180 min per week positively impacts IBS symptoms and PC. Monitoring GPCS in IBS patients provides insights into the connection between physical activity and symptom severity, aiding healthcare professionals in tailoring effective treatment plans.

The Impact of a Twelve-Week Moderate Aerobic Exercise Program on Gastrointestinal Symptom Profile and Psychological Well-Being of Irritable Bowel Syndrome Patients: Preliminary Data from a Southern Italy Cohort.

Walking is popular moderate-intensity aerobic exercise that improves mental and gastrointestinal (GI) health. It can relieve symptoms associated with irritable bowel syndrome (IBS), e.g., intestinal gas, abdominal distension, and bowel disturbances. This study examined the impact of a moderate-intensity aerobic exercise program on the clinical and psychological parameters of IBS patients. In total, 40 IBS patients (11 males and 29 females; mean age 51.9 ± 7.8 years) participated in a 12-week aerobic exercise program. Participants completed questionnaires assessing GI symptoms, psychological profiles, and quality of life (QoL) before and after the intervention. Field tests, anthropometric measurements, and bioimpedance assessments were also conducted. The present findings confirmed a significant improvement in IBS symptoms after the aerobic exercise program. Bloating was the most common symptom and, together with abdominal pain, was significantly reduced after treatment. Psychological and QoL questionnaires indicated decreased anxiety, depression, somatization, and stress levels. Correlations were found between anxiety/depression and the severity of abdominal pain as well as between stress and the severity of abdominal distension. Moderate-intensity aerobic exercise positively impacted GI symptoms and psychological well-being, complementing dietary and psychological support as a non-pharmacological therapy for the management of IBS. These findings emphasize the importance of alternative approaches for IBS treatment.

Lifestyle Modification: Evaluation of the Effects of Physical Activity and Low-Glycemic-Index Mediterranean Diet on Fibrosis Score.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one the most prevalent causes of chronic liver disease worldwide. In the absence of an approved drug treatment, lifestyle modification is the first intervention strategy. This study aimed to estimate the main effect of two different physical activity (PA) programs, and a Low-Glycemic-Index Mediterranean Diet (LGIMD), or their combined effect on liver fibrosis parameters in subjects with NAFLD. METHODS: Subjects with moderate or severe NAFLD grade of severity (n = 144) were randomly assigned to six intervention arms for three months: LGIMD, PA programs, and their combination. Data were collected at baseline, 45 days, and 90 days. Transient elastography was performed to assess the outcome. RESULTS: at 90 days, a statistically significant reduction in kPa was found among subjects following LGMID (-2.85, 95% CI -5.24, -0.45) and those following an LGIMD plus PA1 (-2.37, 95% CI -4.39, -0.35) and LGIMD plus Pa2 (-2.21, 95% CI -4.10, -0.32). The contrast between time 2 and time 1 of the LGIMD plus PA2 treatment showed a statistically significant increase, and vice versa: the contrast between time 3 and time 2 of the same treatment showed a statistically significant reduction. The PA1 and PA2 arms also showed reduced kPa, although the results did not reach statistical significance. CONCLUSIONS: The intervention arms, LGIMD, LGIMD+PA1, and LGIMD+PA2, reduced the fibrosis score.

Diet and Exercise Exert a Differential Effect on Glucose Metabolism Markers According to the Degree of NAFLD Severity.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes (T2D) are highly prevalent diseases worldwide. Insulin Resistance (IR) is the common denominator of the two conditions even if the precise timing of onset is unknown. Lifestyle change remains the most effective treatment to manage NAFLD. This study aimed to estimate the effect of the Low Glycemic Index Mediterranean Diet (LGIMD) and exercise (aerobic and resistance) over a one-year period on the longitudinal trajectories of glucose metabolism regulatory pathways. MATERIALS AND METHODS: In this observational study, 58 subjects (aged 18-65) with different degrees of NAFLD severity were enrolled by the National Institute of Gastroenterology-IRCCS "S. de Bellis", to follow a 12-month program of combined exercise and diet. RESULTS: The mean age was 55 ± 7 years old. Gender was equally distributed among NAFLD categories. There was a statistically significant main effect of time for glycosylated hemoglobin (Hb1Ac) over the whole period (-5.41, 95% CI: -7.51; -3.32). There was a steady, statistically significant decrease of HbA1c in participants with moderate and severe NAFLD whereas this effect was observed after the 9th month in those with mild NAFLD. CONCLUSIONS: The proposed program significantly improves glucose metabolism parameters, especially HbA1c.

The Effect of Low Glycemic Index Mediterranean Diet and Combined Exercise Program on Metabolic-Associated Fatty Liver Disease: A Joint Modeling Approach.

BACKGROUND: Excessive caloric intake and reduced energy expenditure are associated with the onset of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to probe the benefits of a low glycemic index Mediterranean diet (LGIMD) and a combined exercise program (CEP) on MAFLD by monitoring the clinical process through anthropometric measurement, body mass index (BMI), and specific biomarkers, such as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). METHODS: The study was conducted at the National Institute of Gastroenterology, 'S. de Bellis', Italy. Subjects were invited to join the study for 12 months. RESULTS: 54 participants were enrolled. Joint modeling of longitudinal and time-to-event data was applied. Overall, a statistically significant direct effect of LGIMD/CEP adherence on ln (BMI), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a strong statistically significant direct effect of log (BMI) on time-to-event were observed. In addition, a statistically significant direct effect of LGIMD/CEP adherence on ln(HOMA-IR), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a statistically significant direct effect of ln(HOMA-IR) on time-to-event were observed. CONCLUSIONS: LGIMD/CEP significantly improved MAFLD status; in addition, longitudinal BMI and HOMA-IR were good predictors of the disappearance of diagnostic criteria for MAFLD.

Modified WCRF/AICR Score and All-Cause, Digestive System, Cardiovascular, Cancer and Other-Cause-Related Mortality: A Competing Risk Analysis of Two Cohort Studies Conducted in Southern Italy.

BACKGROUND: In real life, nutrition goes beyond purely biological domains. Primary prevention is the most efficient approach for reducing the risk of mortality. We aimed to study the association of lifestyle, as measured by a modified World Cancer Research Fund/American Institute for Cancer Research (mWCRF/AICR) scoring system with all-cause, digestive system disease-related (DSD-related), cardiovascular disease-related (CVD-related), cancer-related and other cause-related mortality using data from two population-based cohort studies conducted in Southern Italy. METHODS: A random sample of 5271 subjects aged 18 years or older was enrolled in 2005-2006 and followed up until 2020. Usual food intakes were estimated using a validated dietary questionnaire. Competing risks survival models were applied. RESULTS: High adherence to the mWCRF/AICR score was found to be statistically significant and negatively associated with all-cause mortality (HR 0.56, 95%CI 0.39; 0.82), DSD-related mortality (SHR 0.38, 95%CI 0.15; 0.97) and cancer-related mortality (SHR 0.43, 95%CI 0.19; 0.97) in the male sub-cohort and other-cause mortality (SHR 0.43, 95%CI 0.21; 0.88) only in the female group. CONCLUSIONS: This mWCRF/AICR score can be seen as a simple, easy tool for use in clinical practice to evaluate both qualitative and quantitative aspects of the diet.