Mild pancreatic fibrosis with preserved exocrine function and increased visceral adipose tissue in m.3243A>G carriers: A magnetic resonance imaging study

Carriers of the mitochondrial variant m.3243 A > G have a high risk of diabetes mellitus and frequently report gastrointestinal symptoms, suggesting a dual endocrine and exocrine pancreas dysfunction. Whether changes in pancreatic morphology, abdominal or ectopic fat distribution contribute to these conditions, remains unknown. Twelve m.3243 A > G carriers with diabetes, 11 carriers without diabetes, and 23 healthy controls underwent abdominal magnetic resonance imaging (MRI). T1 relaxation time and magnetic resonance elastography (MRE) stiffness estimated pancreatic fibrosis. Pancreas volume was assessed by MRI and combined with faecal elastase measurements to evaluate exocrine pancreatic function. The ectopic fat content of muscle and the pancreas was estimated using proton density fat fraction, alongside abdominal fat measurements of cross-sectional areas (CSA) of visceral and subcutaneous adipose tissue. The homeostasis model assessment 2 (HOMA2) was used to estimate insulin resistance (HOMA2-IR). Compared to healthy controls, carriers with diabetes had an increased median [IQR] T1 relaxation time (909 ms [868–1085] vs. 823 ms [785–852], p < 0.001) and MRE stiffness (1.32 kPa [1.24–1.43] vs. 1.23 kPa [1.12–1.28], p = 0.03). There was no difference in pancreas volume or evidence of exocrine pancreatic dysfunction evaluated by faecal elastase. Visceral adipose tissue CSA median [IQR] was increased in m.3243 A > G carriers compared to controls (61.0 cm 2 [26.4–100.9] vs. 27.9 cm 2 [17.2–65.0], p = 0.03) and correlated positively with HOMA2-IR (r s = 0.7, p < 0.001). Increased T1 relaxation time and MRE stiffness indicate mild pancreatic fibrosis in m.3243 A > G carriers with diabetes, without further evidence of exocrine insufficiency. Visceral fat was increased in m.3243 A > G carriers and associated with insulin resistance, implying metabolic dysregulation. • m.3243A > G carriers with diabetes show mild pancreatic fibrosis. • Exocrine pancreatic function is preserved in m.3243 A > G carriers. • Increased visceral adipose tissue in m.3243 A > G carriers is associated with insulin resistance, indicating metabolic dysregulation.