Twentyâ fiveâ year trajectories of insulin resistance and pancreatic βâ cell response and diabetes risk in nonalcoholic fatty liver disease

Abstract

Background & AimsInsulin resistance is a risk marker for nonâ alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and βâ cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in nonâ alcoholic fatty liver disease.MethodsThree thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective biâ racial cohort of adults age 18â 30 years at baseline (1985â 1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010â 2011), nonâ alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25â year trajectories in homeostatic model assessment insulin resistance and βâ cell response homeostatic model assessmentâ β.ResultsThree distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (lowâ stable [47%]; moderateâ increasing [42%]; and highâ increasing [12%]) and homeostatic model assessmentâ β (lowâ decreasing [16%]; moderateâ decreasing [63%]; and highâ decreasing [21%]). Y25 nonâ alcoholic fatty liver disease prevalence was 24.5%. Among nonâ alcoholic fatty liver disease, highâ increasing homeostatic model assessment insulin resistance (referent: lowâ stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0â 31.9) and incident (OR = 10.5, 2.6â 32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, nonâ alcoholic fatty liver disease participants with lowâ decreasing homeostatic model assessmentâ β (referent: highâ decreasing) had the highest odds of prevalent (OR = 14.1, 3.9â 50.9) and incident (OR = 10.3, 2.7â 39.3) diabetes.ConclusionTrajectories of insulin resistance and βâ cell response during young and middle adulthood are robustly associated with diabetes risk in nonâ alcoholic fatty liver disease. Thus, how persons with nonâ 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 nonâ alcoholic fatty liver disease assessment.