Liver Fibrosis Estimated Using Noninvasive Blood Biochemical Indices Is Correlated with Visit-to-Visit Glycated Hemoglobin A1c Variability in Individuals with Type 2 Diabetes

Background/Objectives: Visit-to-visit glycated hemoglobin A1c (HbA1c) variability is associated with cardiovascular diseases (CVDs) and all-cause mortality, independent of mean HbA1c levels. Metabolic dysfunction–associated steatotic liver disease (MASLD) is associated with CVDs and mortality. We aimed to clarify the association between annual HbA1c variability and MASLD development in individuals with type 2 diabetes (T2D). Methods: A retrospective cohort study was conducted in 402 Japanese patients (219 men, 183 women) with T2D. The participants’ HbA1c levels were measured every 2 months, and their HbA1c coefficient of variation (HbA1c-CV) was calculated from the HbA1c in the past year. We statistically evaluated the association between HbA1c-CV and noninvasive clinical indices of MASLD, including the hepatic steatosis index (HSI), fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease fibrosis score (NFS). Results: Multiple regression analysis of clinical variables and each MASLD index showed that all liver fibrosis indices, including the FIB-4 index (p < 0.001), APRI (p = 0.005), and NFS (p < 0.001), were positively correlated with HbA1c-CV, whereas the HSI was not (p = 0.148). These associations remained even after adjusting for the medications used in the participants. Conclusions: The development of liver fibrosis, estimated using noninvasive blood biochemical indices, is independently and positively associated with annual HbA1c-CV in individuals with T2D. This result suggests that a comprehensive approach, including early MASLD risk stratification, may be beneficial for optimal diabetes management.