Pancreas Volume in Individuals with MODY 1, 2, 3, and 5

Individuals with new-onset type 1 diabetes (T1D) have a smaller pancreas volume, which declines further during the first years after diagnosis. Whether this reflects the insulin deficiency associated with T1D or the underlying process leading to T1D is not clear. Mutations in several genes that are active in the pancreas and/or pancreatic islet cells cause varying degrees of insulin deficiency, resulting in Maturity Onset Diabetes of Youth (MODY). To determine whether decreased pancreas volume is associated with these other forms of diabetes, we used a standardized MRI protocol that has been validated in over 500 scans to measure pancreas volume normalized to body weight (pancreas volume index, PVI). Individuals with mutations in HNF4A (MODY 1, ages 19-71, PVI 0.79 ± 0.07 mL/kg, N=4), GCK (MODY 2, ages 9-55, PVI 0.97 ± 0.10 mL/kg, N=5), or HNF1A (MODY 3, ages 16-60, PVI 0.80 ± 0.09 mL/kg, N=7) had pancreas volume similar to controls (ages 8-65, 0.96 ± 0.03 mL/kg, N=78, p>0.59). Pancreas volume was not different in individuals with MODY 1, 2, or 3 who required insulin replacement therapy compared with those not on insulin (PVI 0.82 ± 0.08 vs. 0.89 ± 0.09 mL/kg, N=9 and 7, p=0.56). Individuals with a mutation in HNF1B (MODY 5), a less common mutation that can be associated with pancreatic hypoplasia, had widely variable pancreas volume (PVI 0.90 ± 0.36 mL/kg, N=3). Further studies to assess pancreas size in other forms of MODY are needed and may provide insight into why the pancreas volume is reduced in T1D. Disclosure J.J. Wright: None. J.M. Williams: None. J. Virostko: None. M.A. Hilmes: None. L. Du: None. H. Kang: None. S.W. Greeley: None. W.E. Russell: None. D.J. Moore: None. A.C. Powers: None. Funding JDRF (3-SRA-2019-759-M-B, 3-SRA-2015-102-M-B)