Relative Pancreas Volume Is Reduced in First-Degree Relatives of Patients With Type 1 Diabetes

Objective: Pancreas size is reduced in patients at type 1 diabetes onset and in autoantibody (AAB)-positive donors without diabetes. We sought to determine whether pancreas volume (PV) imaging could improve understanding of the loss of pancreas size in first-degree relatives (FDRs) of patients with type 1 diabetes. We also examined relationships among PV, AAB status, and endocrine and exocrine functions.

Research design and methods: We conducted a cross-sectional study that included five groups: AAB^- control subjects (no diabetes and no first- or second-degree relatives with type 1 diabetes) (N = 49), AAB^- FDRs (N = 61), AAB⁺ FDRs (N = 67 total: n = 31 with a single positive AAB [AAB⁺ single] and n = 36 with multiple positive AABs [AAB⁺ multiple]), and patients with recent-onset type 1 diabetes (<1 year) (N = 52). Fasting subjects underwent 1.5T pancreatic MRI, and PV and relative PV (RPV) (PV-to-BMI ratio) were analyzed between groups and for correlations with HbA_1c, C-peptide, glucose, and trypsinogen.

Results: All FDR groups had significantly lower RPV adjusted for BMI (RPV_BMI) than control subjects (all P < 0.05). Patients with type 1 diabetes had lower RPV_BMI than AAB^- FDR (P < 0.0001) and AAB⁺ multiple (P ≤ 0.013) subjects. Transformed data indicated that trypsinogen levels were lowest in patients with type 1 diabetes.

Conclusions: This study demonstrates, for the first time, all FDRs having significantly smaller RPV_BMI compared with AAB^- control subjects. Furthermore, RPV_BMI was significantly lower in patients with recent-onset type 1 diabetes than in the AAB^- FDR and AAB⁺ multiple groups. As such, RPV_BMI may be a novel noninvasive biomarker for predicting progression through stages of type 1 diabetes risk. This study highlights the potential paracrine relationships between the exocrine and endocrine pancreas in progression to type 1 diabetes in subjects at risk.