Pancreatic Exocrine Changes in Longstanding Type 1 Diabetes

Individuals with longstanding type 1 diabetes (T1D) have smaller pancreata. Recent studies have found that pancreas volume is less at the time of T1D diagnosis and slightly decreased in auto-antibody positive, nondiabetic (ND) individuals. The reduced pancreas size in T1D cannot be due solely to β cell loss, since islets make up only ~2% of total pancreas mass. To better understand the T1D pancreas, we studied the pancreatic endocrine and exocrine compartments from T1D donors (N=23; age 18-62 years; duration 10-45 years) and age-matched, ND controls (N= 20; age 18-55 years). During islet isolation from T1D pancreata, standard approaches and enzymes were quite inadequate to free most islets or disperse the exocrine tissue. We also noted that T1D pancreata were more firm in physical consistency and had reduced relative pancreas weight (RPW, gm pancreas per kg body weight; 0.63 ± 0.04 in T1D vs. 1.1 ± 0.1 in ND, p<0.001) and volume (55.7 ± 7.2 vs. 99.9 ± 9.1 cc, p=0.001, n=21 and 11). The RPW did not correlate with T1D duration. Acinar cell density per tissue section was similar in T1D and ND (7400 ± 306 vs. 7502 ± 247 cells/mm2; n=11 per group; p=0.8), but T1D pancreata had fewer total cells as expressed per pancreatic mass (3.4 ± 1.7 vs. 5.8 ± 0.8 x 1010 cells, p=0.02, n=11 and 10). T1D acinar cells tended toward reduced size compared to ND acinar cells (86.1 ± 2.6 vs. 94.0 ± 3.8 μm2, p=0.055, n=8 and 10); acinar cell size did not correlate with pancreas weight, RPW, or proximity to islets. TUNEL and Ki67-positive exocrine cells were rare in both T1D and ND. Trichrome staining showed a qualitative increase in connective tissue in the exocrine compartment of T1D pancreata compared to ND, though specific staining for collagen IV and laminin appeared similar. Collectively these data illustrate exocrine-specific changes to pancreata in longstanding T1D, including an increase in connective tissue and a reduced pancreas size due to a reduction in total acinar cell number. How, when and why these changes occur in the T1D exocrine compartment remain to be determined. Disclosure J.J. Wright: None. D.C. Saunders: None. J. Lindner: None. M. Bogdani: None. M. Brissova: None. R. Bottino: Research Support; Self; Imagine Pharma. A.C. Powers: None.