Underrecognition of Nonalcoholic Fatty Liver Disease in Poorly Controlled Diabetes

A Call to Action in Diabetes Care

Anastasia-Stefania Alexopoulos; Ryan Duffy; Elizabeth A. Kobe; Jashalynn German; Cynthia A. Moylan; Diana Soliman; Amy S. Jeffreys; Cynthia J. Coffman; Matthew J. Crowley


J Endo Soc. 2021;5(12) 

In This Article

Abstract and Introduction


Individuals with type 2 diabetes (T2DM) are at high risk for nonalcoholic fatty liver disease (NAFLD), and evidence suggests that poor glycemic control is linked to heightened risk of progressive NAFLD. We conducted an observational study based on data from a telehealth trial conducted in 2018–2020. Our objectives were to (1) characterize patterns of NAFLD testing/care in a cohort of individuals with poorly controlled T2DM; and (2) explore how laboratory based measures of NAFLD (eg, liver enzymes, fibrosis-4 [FIB-4]) vary by glycemic control. We included individuals with poorly controlled T2DM (n = 228), defined as hemoglobin A1c (HbA1c) ≥ 8.5% despite clinic-based care. Two groups of interest were (1) T2DM without known NAFLD; and (2) T2DM with known NAFLD. Demographics, medical history, medication use, glycemic control (HbA1c), and NAFLD testing/care patterns were obtained by chart review. Among those without known NAFLD (n = 213), most were male (78.4%) and self-identified as Black race (68.5%). Mean HbA1c was 9.8%. Most had liver enzymes (85.4%) and platelets (84.5%) ordered in the outpatient department over a 2-year period that would allow for FIB-4 calculation, yet only 2 individuals had FIB-4 documented in clinical notes. Approximately one-third had abnormal liver enzymes at least once over a 2-year period, yet only 7% had undergone liver ultrasound and 4.7% had referral to hepatology. Among those with known NAFLD (n = 15), mean HbA1c was 9.5%. Only 4 individuals had undergone transient elastography, half of whom had advanced fibrosis. NAFLD is underrecognized in poorly controlled T2DM, even though this is a high-risk group for NAFLD and its complications.


Nonalcoholic fatty liver disease (NAFLD) disproportionately impacts individuals with type 2 diabetes (T2DM), with a prevalence of 60% to 70%.[1–4] Importantly, the presence of T2DM is associated with higher odds of having progressive forms of NAFLD[5,6] such as nonalcoholic steatohepatitis and advanced liver fibrosis, with a prevalence as high as 10% to 15% for advanced fibrosis in T2DM.[3,4] T2DM also leads to a substantial increase in the risk of NAFLD complications, including a 2-fold increase in hepatocellular carcinoma and liver-related mortality risk.[7,8] Recent evidence also suggests that beyond the presence of T2DM, glycemic control may be linked to greater severity of liver fibrosis in NAFLD.[9] Therefore, individuals with poor glycemic control may be at particular risk of progressive NAFLD and poor liver outcomes.

Despite an increasing clinical burden of NAFLD, and calls to action across the medical community to prepare for this rising public health threat,[10–14] NAFLD remains underrecognized in primary care settings.[15] It is likely that this underrecognition extends to T2DM populations—even in those with poor glycemic control—though data specific to poorly controlled T2DM are lacking. The primary purpose of this study was to examine NAFLD testing and care patterns in a cohort of individuals with poorly controlled T2DM. Since laboratory-based measures (liver enzymes, noninvasive scores, eg, fibrosis-4 [FIB-4] index) constitute initial testing for NAFLD that may prompt additional work-up, we also aimed to explore how these measures vary by glycemic control.