Non-alcoholic fatty liver disease (NAFLD) in type 1 diabetes: – from a clinical perspective –

Abstract

Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is increasingly prevalent worldwide, paralleling the rise in obesity and diabetes. NAFLD encompasses a spectrum of liver conditions, starting with isolated fat accumulation in liver cells (steatosis), which can progress to inflammation (non-alcoholic steatohepatitis, NASH), fibrosis, cirrhosis, and eventually liver failure or hepatocellular carcinoma. The global prevalence of NAFLD has risen from 25% to 38%, with fibrosis observed in 8% of the population. Major risk factors include insulin resistance and adipose tissue dysfunction, making individuals with type 2 diabetes and obesity particularly vulnerable. NAFLD prevalence in type 2 diabetes is notably higher, with 68% for steatosis and 25% for fibrosis. Traditionally, type 1 and type 2 diabetes have been seen as distinct conditions, but they share features such as insulin resistance, hyperglycemia, systemic hyperinsulinemia, and chronic low-grade inflammation. Obesity is also becoming increasingly common in type 1 diabetes. This raises the question of whether individuals with type 1 diabetes are also at high risk for NAFLD and its advanced stages. In Part I we focus on the prevalence of NAFLD and its association with insulin resistance. Chapter 2 presents a systematic review and meta-analysis of NAFLD prevalence in type 1 diabetes. Based on 20 studies, the pooled prevalence was 19%, higher (22%) in studies focusing on adults. Prevalence varied by diagnostic method, with ultrasound studies reporting 25.4% and MRI studies only 5.2%. Chapter 3 examines NAFLD in the DILIVER cohort of 150 patients with type 1 diabetes using transient elastography (TE). NAFLD prevalence was 20%, with fibrosis in 6.7% and advanced fibrosis in 2.0%. Insulin resistance, measured via estimated glucose disposal rate (eGDR), was significantly associated with NAFLD. Chapter 4 compares NAFLD prevalence in type 1 versus type 2 diabetes using the DILIVER cohort and a type 2 diabetes cohort. NAFLD prevalence was significantly higher in type 2 diabetes (76% vs. 20%), as was advanced fibrosis (22% vs. 2.0%). While etiological factors (e.g., BMI, metabolic syndrome, insulin sensitivity) were associated with NAFLD in both groups, the strength of these associations was similar across subtypes. In Part II the focus is on daily practice. Chapter 5 explores the role of physical activity in preventing NAFLD. No dose-response relationship was found between total physical activity and insulin resistance or NAFLD. However, individuals engaging in regular sports had lower rates of insulin resistance and NAFLD, suggesting sports participation as proxy for overall healthy lifestyle. Chapter 6 evaluates anthropometric and non-invasive diagnostic tools. Combining waist circumference and the fatty liver index (FLI) proved effective in ruling out NAFLD. TE remains essential for confirming steatosis or fibrosis in at-risk patients. Considering implications and future research this thesis highlights the importance of recognizing NAFLD risk in type 1 diabetes and tailoring diagnostic and preventive strategies accordingly. Lifestyle interventions, particularly sports participation, should be emphasized, and routine clinical measures like waist circumference and FLI could guide targeted testing. Future research should explore NAFLD's pathophysiology in type 1 diabetes and evaluate tailored treatment approaches.