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Nonalcoholic Fatty Liver Disease in The Rotterdam Study: About Muscle Mass, Sarcopenia, Fat Mass, and Fat Distribution.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Obesity is a major risk factor for NAFLD and recently, low skeletal muscle mass emerged as additional risk factor for NAFLD. However, the different contributions of body mass index (BMI) to the risk of NAFLD are not yet well-known. We therefore studied body composition and muscle function with NAFLD in an elderly population-based study. Participants of European descent underwent dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography. NAFLD was defined as liver steatosis in absence of secondary causes for steatosis. Skeletal muscle index (SMI) was defined as appendicular lean mass/height² and (pre)sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus guidelines. All analyses were stratified by sex and BMI (cut point: 25?kg/m² ) and adjusted for age, weight, height, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and android-fat-to-gynoid-fat ratio (AGR). We included 4609 participants, of whom 1623 had NAFLD (n?=?161 normal-weight and n?=?1462 overweight). Presarcopenia and sarcopenia prevalence was low (5.9% and 4.5%, respectively) and both were not associated with NAFLD. SMI was associated with less NAFLD in normal-weight women (OR, 0.48; 95% CI, 0.29 to 0.80). A similar association for SMI and NAFLD was seen in normal-weight men, but significance dissipated after adjustment for AGR (OR, 0.63; 95% CI, 0.39 to 1.02). Generally, fat mass was a better predictor for NAFLD than lean mass. In particular, android fat mass was associated with all NAFLD subgroups (OR from 1.77 in overweight men to 8.34 in normal-weight women, p_max =?0.001), whereas substitution of gynoid fat mass for other body components had a significant protective association with NAFLD in every subgroup, but normal-weight men. Likewise, AGR was the best performing predictor for NAFLD prevalence (OR from 1.97 in normal-weight men to 4.81 in normal-weight women, p_max

SUBMITTER: Alferink LJM

PROVIDER: S-EPMC6852390 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Project description:Background: Recent studies in adult non-elderly and elderly individuals have reported a link between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. Nonetheless, whether this relationship would be found outside these populations it is still unknown. Hence, we evaluated the relationship between NAFLD and skeletal muscle mass in children and adolescents with overweight/obesity. Methods: Two-hundred and thirty-four overweight/obese youths were enrolled. NAFLD was diagnosed by ultrasononography, after exclusion of infectious and metabolic disorders. Forty of the patients with NAFLD had also liver biopsy. Total and regional lean body mass and total fat mass measurements were obtained by dual-energy X-ray absorptiometry. The relative muscle mass (RMM) was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat (kg) mass. Appendicular skeletal muscle mass (ASM) was calculated by the sum of muscle masses of the four limbs (kg), and expressed as percent of body weight. Results: Subjects were stratified according to tertiles of RMM. The prevalence of abdominal obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD as well as biopsy-proven nonalcoholic steatohepatitis (NASH) was significantly increased in the lowest tertile of RMM. After controlling for age, sex and Tanner stage, children in the lowest tertile of RMM had an increased risk for NAFLD (OR= 2.80, 95% CI=1.57-5.02) compared to those in the other two tertiles. This association persisted after additional adjustments for clinical and metabolic variables. Similarly, the risk of NAFLD in the lowest tertile of ASM/weight index was significantly higher compared to those in the other two tertiles after adjustment for the above confounders. Conclusions: This is the first study to establish an independent association between low muscle mass and NAFLD/NASH in overweight/obese youths. Considering the worldwide increase of pediatric obesity, measurements of muscle mass may serve as useful method of identifying among obese children those at high metabolic risk who may need intensive lifestyle interventions to prevent NAFLD and its progression.

Project description:IntroductionThe disease burden of nonalcoholic fatty liver disease (NAFLD) increases rapidly, in line with the obesity pandemic. Physical activity has been linked to a lower risk of NAFLD. However, the impact of different intensities of activity and sedentary behavior and whether their effects on NAFLD are explained by metabolic health remain unclear.MethodsWe performed cross-sectional analyses within the population-based Rotterdam Study cohort. Abdominal ultrasound and accelerometry data were collected between 2009 and 2014. NAFLD was defined as hepatic steatosis diagnosed by ultrasound, in the absence of secondary causes for steatosis: viral hepatitis, steatogenic drugs, and excessive alcohol. We categorized accelerometry data into sedentary time and light, moderate, and vigorous physical activities.ResultsWe included 667 participants (aged 63.3 ± 6.3 years, 53% female individuals), and 34.3% had NAFLD. Total physical activity was associated with lower NAFLD prevalence adjusted for demographic, lifestyle, and socioeconomic factors (odds ratio: 0.958 per 10 min/d, 95% confidence interval [CI]: 0.929-0.986). More intensive physical activity was more strongly associated with lower NAFLD prevalence: odds ratios for light, moderate, and vigorous physical activities were 0.931 (95% CI: 0.882-0.982), 0.891 (95% CI: 0.820-0.967), and 0.740 (95% CI: 0.600-0.906) per 10 min/d, respectively. These associations were explained by metabolic health, particularly homeostatic model assessment of insulin resistance (proportion mediated: 0.59, P < 0.001) and waist circumference (proportion mediated: 1.08, P < 0.001). Beyond this indirect effect, no direct effect could be demonstrated (P = 0.282-0.827).DiscussionPhysical activity at each intensity is inversely associated with NAFLD prevalence, with larger effects for higher intensities of physical activity. This association is mediated by better metabolic health, mainly lower insulin resistance and waist circumference. Physical activity should therefore be incorporated into NAFLD disease management and prevention programs.

Project description:Background and objectivesNonalcoholic fatty liver disease (NAFLD) might affect brain health via the so-called liver-brain axis. Whether this results in an increased risk for dementia remains unclear. Therefore, we investigated the association of NAFLD and fibrosis with incident dementia and cognition among the elderly.MethodsWe performed longitudinal and cross-sectional analyses within the Rotterdam Study, an ongoing prospective cohort. Participants visiting between 1997 and 2002 with available fatty liver index (FLI) (set 1) or participants visiting between 2009 and 2014 with abdominal ultrasound (set 2) and liver stiffness (set 3) were included. Exclusion criteria were secondary causes for steatosis, prevalent dementia, and missing alcohol data. NAFLD was defined as FLI ≥60 or steatosis on ultrasound and fibrosis as liver stiffness ≥8.0 kPa. Dementia was defined according to the DSM-III-R. Associations between NAFLD, fibrosis, or liver stiffness and incident dementia were quantified using Cox regression. Finally, the association between NAFLD and cognitive function was assessed cross-sectionally.ResultsSet 1 included 3,975 participants (age 70 years, follow-up 15.5 years), set 2 4,577 participants (age 69.9 years, follow-up 5.7 years), and set 3 3,300 participants (age 67.6 years, follow-up 5.6 years). NAFLD and fibrosis were consistently not associated with an increased risk for dementia (NAFLD based on ultrasound, hazard rate [HR] 0.84, 95% CI 0.61-1.16; NAFLD based on FLI, HR 0.92, 95% CI 0.69-1.22; fibrosis, HR 1.07, 95% CI 0.58-1.99) in fully adjusted models. Of interest, NAFLD was associated with a significantly decreased risk for incident dementia until 5 years after FLI assessment (HR 0.48; 95% CI 0.24-0.94). Moreover, NAFLD was not associated with worse cognitive function, covering several domains.ConclusionsNAFLD and fibrosis were not associated with an increased risk for incident dementia, nor was NAFLD associated with impaired cognitive function. In contrast, NAFLD was even protective in the first 5 years of follow-up, hinting toward NAFLD regression before dementia onset.Trial registration informationClinical Trial Number: NTR6831.

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Nonalcoholic Fatty Liver Disease in The Rotterdam Study: About Muscle Mass, Sarcopenia, Fat Mass, and Fat Distribution.

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