Glycated Hemoglobin Is Suboptimal for the Screening of Prediabetes and Type 2 Diabetes in Adults With Nonalcoholic Fatty Liver Disease.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but T2D screening tests are not well validated in this population. In this study, we assessed performance of glycated hemoglobin (A1C) and fasting plasma glucose (FPG) in glucose dysmetabolism screening and aimed to optimize detection thresholds for individuals with NAFLD.

Methods: We retrospectively included oral glucose tolerance tests (OGTTs) from consecutive patients undergoing a specialized clinic for NAFLD, if A1C and/or fasting glucose was available within 3 months of OGTT. We compared performances of A1C and fasting glucose with the "gold standard" of OGTT using thresholds from the 2018 Diabetes Canada guidelines. A1C and FPG thresholds were optimized for detection of glucose dysmetabolism using receiver operating characteristic curves.

Results: We included 63 OGTTs from individuals with NAFLD (52% female, age 48 [interquartile range 35 to 63] years, body mass index 34 [interquartile range 29 to 40] kg/m). A1C had 16% (95% confidence interval [CI] 6% to 38%) sensitivity (Se) and 97% (95% CI 85% to 100%) specificity (Sp) for T2D detection, and 45% (95% CI 30% to 62%) Se and 100% (95% CI 83% to 100%) Sp for abnormal blood glucose detection. FPG had 67% (95% CI 45% to 83%) Se and 100% (95% CI 92% to 100%) Sp for T2D detection, and 74% (95% CI 59% to 85%) Se and 92% (95% CI 74% to 99%) Sp for abnormal blood glucose detection. Optimal A1C and FPG thresholds were 5.6% and 6.3 mmol/L for T2D detection, which are lower than current recommendations.

Conclusions: A1C is less sensitive than FPG and is suboptimal for T2D detection, suggesting that OGTT may be obtained if A1C is ≥5.6% or FPG is ≥6.3 mmol/L in individuals with NAFLD, to avoid underdiagnosis and treatment inertia.