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

Abstract

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 HbA1c, C-peptide, glucose, and trypsinogen. RESULTS All FDR groups had significantly lower RPV adjusted for BMI (RPVBMI) than control subjects (all P < 0.05). Patients with type 1 diabetes had lower RPVBMI 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 RPVBMI compared with AAB− control subjects. Furthermore, RPVBMI was significantly lower in patients with recent-onset type 1 diabetes than in the AAB− FDR and AAB+ multiple groups. As such, RPVBMI 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.