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. 2019 Feb;42(2):281-287.
doi: 10.2337/dc18-1512. Epub 2018 Dec 14.

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

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Free PMC article

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

Martha L Campbell-Thompson et al. Diabetes Care. .
Free PMC article

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.

Trial registration: ClinicalTrials.gov NCT02234947.

Figures

Figure 1
Figure 1
RPVBMI by age. RPVBMI increased with age to ∼25 years of age in all study groups and then plateaued. Subjects in the group with recent-onset type 1 diabetes had the lowest RPVBMI trends by age.
Figure 2
Figure 2
Model-estimated mean (95% CI) RPVBMI by study group. Model-estimated mean RPVBMI was significantly different between control subjects and all other groups; a linear trend test was significant. The model adjusted for age and sex and accounted for individuals from the same family. Mean RPVBMI for AAB FDR subjects was significantly lower than for control subjects and significantly higher than for patients with recent-onset type 1 diabetes (T1D). Mean RPVBMI for AAB+ multiple subjects was significantly different from that for patients with recent-onset type 1 diabetes.

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