Detecting prediabetes using an oral insulin-glucose tolerance test in nonalcoholic fatty liver disease patients without diabetes

Purpose: Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in Western societies and is described as the hepatic component of the Metabolic Syndrome. The global epidemic of non-alcoholic fatty liver disease (NAFLD) has led to the recognition of its associated risks of cardiovascular disease, diabetes, cirrhosis, hepatocellular carcinoma and ultimately liver failure requiring liver transplantation. Recent reports of the high prevalence of NAFLD and NASH in people with diabetes led us to hypothesize that NAFLD patients without diabetes were likely to have prediabetes and thus would represent a target population for strategies to prevent diabetes. The aim of this study is to identify metabolic parameters indicative of risk of progression to type 2 diabetes in non-diabetic patients with NAFLD. Methods: We characterized sequential patients referred to the Metabolic Liver Clinic, with metabolic parameters and identifying steatosis as measured using NASH FibroSURE®. Retrospective review of 170 sequential referrals to the Metabolic Liver Clinic between 2010-2014. Glucoregulatory status was assessed by measuring A1c levels and by administering an oral glucose tolerance test with glucose and insulin levels measured at 0, 30, 60, 90, and 120 minutes. In addition, c-peptide and proinsulin were measured at 0 and 30 minutes. Those that met criteria for diabetes were excluded. We assessed correlations between metabolic parameters. Spearman correlation coefficient was used to measure the association between metabolic parameters and NASH FibroSURE® scores. Results: The prevalence of prediabetes was 43% among NAFLD patients without type 2 diabetes. The oral insulin-glucose tolerance test detected 47% patients who had normal standard tests recommended by American Diabetes Association (ADA) (A1c, fasting plasma glucose, and 2-hour post 75gram load glucose). Statistically significant correlations were found between metabolic parameters including steatosis score vs. BMI (p \u3c0.0001), and steatosis score vs. A1c (p=0.0001). The oral insulin-glucose tolerance test was more effective than the standard glucose tolerance test at identifying NAFLD prediabetics and was superior to single measurements of A1c, glucose, or insulin. Conclusions: Insulin resistance is already present in NAFLD patients without diabetes. Fasting glucose plus two-hour postprandial glucose, fasting insulin or A1c are insufficient for detecting risk of hyperinsulinemia and insulin resistance in patients with NAFLD. Insulin levels need to be measured within the 2-hour 75g oral glucose tolerance test in NAFLD patients without diabetes mellitus