Individuals with new-onset type 1 diabetes (T1D) and those at risk for T1D have a smaller pancreas. The reason for the reduced pancreas size and acinar cell number in T1D is not known, with possible explanations being a direct effect of insulin deficiency, acinar cell-directed autoimmunity, or cytokine-mediated inflammation. To test the hypothesis that insulin deficiency leads to reduced pancreas size, we measured pancreas volume in a family with monogenic diabetes due to an INS-gene mutation using a standardized MRI protocol developed as part of the Multicenter Assessment of the Pancreas in Type 1 Diabetes program (MAP-T1D, www.map-t1d.com, PMID: 34428220) . Pancreas volume was normalized to body weight to calculate pancreas volume index (PVI) . The family, carrying a heterozygous c.94G>C (p.Gly32Arg) INS mutation, was identified as part of the Monogenic Diabetes Registry at the University of Chicago. All family members with diabetes, including the father, diagnosed at age 22, and three children, diagnosed before 8 months, have clinical insulin deficiency and are treated with insulin. All four family members with diabetes (age 30, 30, 34, and 62 yrs; BMI 23-28; PVI 0.23, 0.42, 0.53, and 0.48 mL/kg) had small PVI compared to those without diabetes (age 32, 38, and 60 yrs; BMI 19-23; PVI 1.07, 1.17, and 0.92, p<0.01) . The pancreas of family members with diabetes was similar to those seen in individuals with new-onset T1D (age 13.4 ± 4.1 years, BMI 20.5 ± 4.1, PVI 0.68 ± 0.22) , and pancreas of family members without diabetes was similar to those of unrelated controls (age 15.9 ± 6.7 years, BMI 21.4 ± 4.4, PVI 0.97 ± 0.22 ml/kg; PMID: 30552135) . Studies in this family indicate that insulin is a determinant of pancreas size either directly as a trophic factor or indirectly through control of other islet-derived growth factors. This relationship suggests that reduced pancreas volume in T1D may be an earlier indicator of local insulin loss rather than a reflection of immune or inflammatory factors.
J.J.Wright: None. J.M.Williams: None. S.W.Greeley: None. A.C.Powers: None. J.Virostko: None. D.J.Moore: None.