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 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.