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

Abstract

OBJECTIVEPancreas 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 METHODSWe conducted a cross-sectional study that included five groups: AAB 2 control subjects (no diabetes and no firstor second-degree relatives with type 1 diabetes) (N = 49), AAB 2 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. RESULTSAll 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 2 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. CONCLUSIONSThis study demonstrates, for the first time, all FDRs having significantly smaller RPV BMI compared with AAB 2 control subjects. Furthermore, RPV BMI was significantly lower in patients with recent-onset type 1 diabetes than in the AAB 2 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.Despite advances in medical diagnosis and treatment, type 1 diabetes remains one of the costliest diseases in the U.S. in terms of health care dollars spent for diabetesrelated costs (1). Immunotherapy-based intervention trials carried out in patients with new-onset type 1 diabetes have demonstrated potential for short-term benefit (e.g., anti-CD20, anti-CD3, and cytotoxic T-lymphocyte-associated antigen 4 Ig) but have failed to demonstrate long-term efficacy (2,3). The inability to provide long-term preservation of b-cell function or prevent type 1 diabetes may stem from unanswered

In-vivo assessment of T cell kinetics in individuals at risk for type 1 diabetes

“…However, in this small cohort we did not detect an association of T reg turnover rate by F max with individual genetic variants in the IL2RA , IL2/IL21 and PTPN2 loci that have been associated with risk for T1D. Other studies also find phenotypical differences between unaffected relatives and controls; one report demonstrated that T1D family members have an elevated inflammatory state and another found small pancreas volume in family members compared with non‐family members as controls .…”

“…The subjects were divided into four groups, with Ctrl = normal control, 0 = relatives without autoantibody, 1 = relatives with one autoantibody and ≥ 2 = relatives with two or more autoantibodies; n = 38 (two participants, including one from the 0 antibody group and one from the two or more antibodies group, were excluded from the analysis due to poor quality of T cell sorting). demonstrated that T1D family members have an elevated inflammatory state [11] and another found small pancreas volume in family members compared with non-family members as controls [12]. We previously demonstrated that individuals with clinically overt T1D had increased CD4 memory T cell turnover [6]; however, we did not find this in autoantibody-positive relatives of those with T1D, suggesting that increased CD4 proliferation only occurs later in disease progression.…”

No acute pancreatitis but reduced exocrine pancreatic function at diagnosis of type 1 diabetes in children

“…Thus, a third of the diabetic patients had abnormally low exocrine pancreas function, which could depend on previous mild pancreatitis and/or abnormally small pancreas as small pancreas size has been found to correlate with decrease exocrine function . The small size of pancreas in children who later get T1D might either depend on decreased insulin production with the secondary consequence of less growth of pancreas, or be a consequence of a genetic background, which is supported by the fact that the size of pancreas seems to be reduced also in relatives of patients with T1D . In some cases, the low amylase values could also be related to low food intake in connection with ketoacidosis.…”

“…In addition, studies show that pancreas often is smaller in patients who develop T1D, although the same smaller size also is seen in first‐degree relatives of patients with T1D …”

From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: New concepts on the stage

“…Finally, in a recent study evaluating PV by MRI, Campbell‐Thompson ML et al described for the first time a significantly lower PV adjusted for BMI (PV‐to‐BMI ratio) in non‐diabetic T1D first‐degree relatives (FDRs) with or without one/multiple autoantibodies positivity compared with unrelated control subjects. Moreover, patients with recent‐onset T1D showed lower PV‐to‐BMI ratio compared with FDRs …”