Abstract
In neonatal diabetes mellitus resulting from mutations in EIF2AK3, PTF1A, HNF1B, PDX1 or RFX6, pancreatic aplasia or hypoplasia is typical. In maturity-onset diabetes mellitus of the young (MODY), mutations in HNF1B result in aplasia of pancreatic body and tail, and mutations in CEL lead to lipomatosis. The pancreas is not readily accessible for histopathological investigations and pancreatic imaging might, therefore, prove important for diagnosis, treatment, and research into these β-cell diseases. Advanced imaging techniques can identify the pancreatic features that are characteristic of inherited diabetes subtypes, including alterations in organ size (diffuse atrophy and complete or partial pancreatic agenesis), lipomatosis and calcifications. Consequently, in patients with suspected monogenic diabetes mellitus, the results of pancreatic imaging could help guide the molecular and genetic investigation. Imaging findings also highlight the critical roles of specific genes in normal pancreatic development and differentiation and provide new insight into alterations in pancreatic structure that are relevant for β-cell disease.
Key Points
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Monogenic (caused by a mutation in only one gene) diabetes mellitus accounts for 1–2% of all diabetes cases
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The mutations associated with monogenic diabetes mellitus usually occur in genes with a regulatory role in pancreatic development and/or β-cell function
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Pancreatic aplasia or hypoplasia is common in patients with neonatal diabetes mellitus caused by mutations in EIF2AK3, PTF1A, HNF1B, PDX1, or RFX6
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Mutations in HNF1B or CEL lead to pancreatic body and tail aplasia or lipomatosis, respectively, which both occur in maturity-onset diabetes mellitus of the young (MODY)
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Alterations in pancreatic structure and size—demonstrated by imaging—might underlie β-cell dysfunction observed in patients with monogenic diabetes mellitus
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Advanced pancreatic imaging methods could prove important for diagnosis, treatment, and research in all β-cell diseases
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The authors' research is supported in part by funds from the Research Council of Norway, the University of Bergen, Innovest, Bergen Medical Research Foundation and Helse Vest.
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Haldorsen, I., Ræder, H., Vesterhus, M. et al. The role of pancreatic imaging in monogenic diabetes mellitus. Nat Rev Endocrinol 8, 148–159 (2012). https://doi.org/10.1038/nrendo.2011.197
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