Mi Na Kim1, Chun-Han Lo2, Kathleen E Corey3, Po-Hong Liu4, Wenjie Ma5, Xuehong Zhang6, Manol Jovani5, Mingyang Song7, Andrew T Chan8, Tracey G Simon9. 1. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea. 2. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America. 3. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. 4. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. 5. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. 6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America. 7. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America. 8. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, United States of America; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America. Electronic address: achan@mgh.harvard.edu. 9. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America. Electronic address: tgsimon@mgh.harvard.edu.
Abstract
BACKGROUND & AIMS: Obesity is established as a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the influence of dynamic changes in adiposity over the life course on NAFLD risk remains poorly understood. METHODS: We collected data from 110,054 women enrolled in the Nurses' Health Study II cohort. Early adulthood weight was ascertained at age 18 years, and weight gain since early adulthood was defined prospectively every 2 years. We used a group-based modeling approach to identify five trajectories of body shape from age 5 years up to age 50 years. NAFLD was defined by physician-confirmed diagnoses of fatty liver, after excluding excess alcohol intake and viral hepatitis, using validated approaches. RESULTS: We documented 3798 NAFLD cases over a total of 20 years of follow-up. Compared to women who maintained stable weight (±2 kg), women with ≥20 kg of adulthood weight gain had the multivariable aHR of 6.96 (95% CI, 5.27-9.18), and this remained significant after further adjusting for early adulthood BMI and updated BMI (both P trend <0.0001). Compared to women with a medium-stable body shape trajectory, the multivariable aHRs for NAFLD were, 2.84 (95% CI, 2.50-3.22) for lean-marked increase, 2.60 (95% CI, 2.27-2.98) for medium-moderate increase, and 3.39 (95% CI, 2.95-3.89) for medium-marked increase. CONCLUSIONS: Both early adulthood weight gain and lifetime body shape trajectory were significantly and independently associated with excess risk of developing NAFLD in mid-life. Maintaining both lean and stable weight throughout life may offer the greatest benefit for the prevention of NAFLD.
BACKGROUND & AIMS: Obesity is established as a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the influence of dynamic changes in adiposity over the life course on NAFLD risk remains poorly understood. METHODS: We collected data from 110,054 women enrolled in the Nurses' Health Study II cohort. Early adulthood weight was ascertained at age 18 years, and weight gain since early adulthood was defined prospectively every 2 years. We used a group-based modeling approach to identify five trajectories of body shape from age 5 years up to age 50 years. NAFLD was defined by physician-confirmed diagnoses of fatty liver, after excluding excess alcohol intake and viral hepatitis, using validated approaches. RESULTS: We documented 3798 NAFLD cases over a total of 20 years of follow-up. Compared to women who maintained stable weight (±2 kg), women with ≥20 kg of adulthood weight gain had the multivariable aHR of 6.96 (95% CI, 5.27-9.18), and this remained significant after further adjusting for early adulthood BMI and updated BMI (both P trend <0.0001). Compared to women with a medium-stable body shape trajectory, the multivariable aHRs for NAFLD were, 2.84 (95% CI, 2.50-3.22) for lean-marked increase, 2.60 (95% CI, 2.27-2.98) for medium-moderate increase, and 3.39 (95% CI, 2.95-3.89) for medium-marked increase. CONCLUSIONS: Both early adulthood weight gain and lifetime body shape trajectory were significantly and independently associated with excess risk of developing NAFLD in mid-life. Maintaining both lean and stable weight throughout life may offer the greatest benefit for the prevention of NAFLD.
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