, a bio/informatics shared resource is still "open for business" - Visit the CDS website


Twenty-five-year trajectories of insulin resistance and pancreatic β-cell response and diabetes risk in nonalcoholic fatty liver disease.

VanWagner LB, Ning H, Allen NB, Siddique J, Carson AP, Bancks MP, Lewis CE, Carr JJ, Speliotes E, Terrault NA, Rinella ME, Vos MB, Lloyd-Jones DM
Liver Int. 2018 38 (11): 2069-2081

PMID: 29608255 · PMCID: PMC6557126 · DOI:10.1111/liv.13747

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.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MeSH Terms (20)

Adolescent Adult Blood Glucose Body Mass Index Diabetes Mellitus Female Humans Insulin-Secreting Cells Insulin Resistance Logistic Models Longitudinal Studies Male Multivariate Analysis Non-alcoholic Fatty Liver Disease Prevalence Prospective Studies Risk Factors Tomography, X-Ray Computed United States Young Adult

Connections (1)

This publication is referenced by other Labnodes entities:

Links