Lisa B VanWagner1,2, Hongyan Ning2, Norrina B Allen2, Juned Siddique2, April P Carson3, Michael P Bancks2, Cora E Lewis4, John Jeffrey Carr5, Elizabeth Speliotes6, Norah A Terrault7, Mary E Rinella1, Miriam B Vos8, Donald M Lloyd-Jones2,9. 1. Division of Gastroenterology & Hepatology, Northwestern University, Chicago, IL, USA. 2. Department of Preventive Medicine, Northwestern University, Chicago, IL, USA. 3. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. 4. Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 5. Department of Radiology, Vanderbilt University, Nashville, TN, USA. 6. Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA. 7. Division of Gastroenterology, University of California at San Francisco, San Francisco, CA, USA. 8. Division of Gastroenterology, Department of Pediatrics, Emory University, Atlanta, GA, USA. 9. Division of Cardiology, Northwestern University, Chicago, IL, USA.
Abstract
BACKGROUND & AIMS: Insulin resistance is a risk marker for non-alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β-cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non-alcoholic fatty liver disease. METHODS: Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi-racial cohort of adults age 18-30 years at baseline (1985-1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010-2011), non-alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25-year trajectories in homeostatic model assessment insulin resistance and β-cell response homeostatic model assessment-β. RESULTS: Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low-stable [47%]; moderate-increasing [42%]; and high-increasing [12%]) and homeostatic model assessment-β (low-decreasing [16%]; moderate-decreasing [63%]; and high-decreasing [21%]). Y25 non-alcoholic fatty liver disease prevalence was 24.5%. Among non-alcoholic fatty liver disease, high-increasing homeostatic model assessment insulin resistance (referent: low-stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0-31.9) and incident (OR = 10.5, 2.6-32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non-alcoholic fatty liver disease participants with low-decreasing homeostatic model assessment-β (referent: high-decreasing) had the highest odds of prevalent (OR = 14.1, 3.9-50.9) and incident (OR = 10.3, 2.7-39.3) diabetes. CONCLUSION: Trajectories of insulin resistance and β-cell response during young and middle adulthood are robustly associated with diabetes risk in non-alcoholic fatty liver disease. Thus, how persons with non-alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non-alcoholic fatty liver disease assessment.
BACKGROUND & AIMS: Insulin resistance is a risk marker for non-alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β-cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non-alcoholic fatty liver disease. METHODS: Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi-racial cohort of adults age 18-30 years at baseline (1985-1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010-2011), non-alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25-year trajectories in homeostatic model assessment insulin resistance and β-cell response homeostatic model assessment-β. RESULTS: Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low-stable [47%]; moderate-increasing [42%]; and high-increasing [12%]) and homeostatic model assessment-β (low-decreasing [16%]; moderate-decreasing [63%]; and high-decreasing [21%]). Y25 non-alcoholic fatty liver disease prevalence was 24.5%. Among non-alcoholic fatty liver disease, high-increasing homeostatic model assessment insulin resistance (referent: low-stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0-31.9) and incident (OR = 10.5, 2.6-32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non-alcoholic fatty liver disease participants with low-decreasing homeostatic model assessment-β (referent: high-decreasing) had the highest odds of prevalent (OR = 14.1, 3.9-50.9) and incident (OR = 10.3, 2.7-39.3) diabetes. CONCLUSION: Trajectories of insulin resistance and β-cell response during young and middle adulthood are robustly associated with diabetes risk in non-alcoholic fatty liver disease. Thus, how persons with non-alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non-alcoholic fatty liver disease assessment.
Authors: Yoshihisa Kodama; Chaan S Ng; Tsung T Wu; Gregory D Ayers; Steven A Curley; Eddie K Abdalla; Jean Nicolas Vauthey; Chusilp Charnsangavej Journal: AJR Am J Roentgenol Date: 2007-05 Impact factor: 3.959
Authors: Emily D Parker; Kathryn H Schmitz; David R Jacobs; Donald R Dengel; Pamela J Schreiner Journal: Am J Public Health Date: 2007-02-28 Impact factor: 9.308
Authors: Michael P Bancks; Mercedes R Carnethon; Lisa S Chow; Samuel S Gidding; David R Jacobs; Satoru Kishi; Joao Lima; Donald Lloyd-Jones; Jared P Reis; Pamela J Schreiner; Rachel Zmora; Norrina B Allen Journal: J Diabetes Complications Date: 2019-02-06 Impact factor: 3.219
Authors: Ronald B Goldberg; Mark T Tripputi; Edward J Boyko; Matthew Budoff; Zsu-Zsu Chen; Jeanne M Clark; Dana M Dabelea; Sharon L Edelstein; Robert E Gerszten; Edward Horton; Kieren J Mather; Leigh Perreault; Marinella Temprosa; Amisha Wallia; Karol Watson; Zeb Irfan Journal: J Clin Endocrinol Metab Date: 2021-10-21 Impact factor: 5.958
Authors: Patrick T Campbell; Lisa B VanWagner; Laura A Colangelo; Cora E Lewis; Anne Henkel; Veeral H Ajmera; Donald M Lloyd-Jones; Douglas E Vaughan; Sadiya S Khan Journal: Liver Int Date: 2020-03-11 Impact factor: 5.828