Figure 1. Diabetic enteropathy in long-standing T1D is characterized by intestinal mucosa abnormalities and impairment in colonic stem cells.
A, B, C. Bar graphs depict the score of diarrhea, abdominal pain and constipation according to the administration of the GSRS questionnaire in healthy subjects (CTRL) and long-standing T1D individuals (T1D+ESRD). Gray area indicates normal range for the parameter. D, E, F. Bar graphs report the measurements of anorectal sphincter contracting tone (mmHg), reflex response (ml) and urgency volume (ml) by anorectal manometry in healthy subjects (CTRL) and longstanding T1D individuals (T1D+ESRD). Gray area indicates normal range for the parameter. n=20 CTRL and n=60 T1D+ESRD individuals were included in the evaluation. G1-G2, I1-I2, K1-K2, M1-M2, O1-O2, Q1-Q2. Representative images of hematoxylin and eosin (H&E) histology staining, immunoreactive Ki67+ cells (MIB1+), ultrastructural analysis of neural structures with red arrows indicating localization and presence of neuroendocrine vesicles, immunohistochemical expression of 5HT, aldehyde dehydrogenase (Aldh)+ cells, and EphB2+ expression, on bioptic samples obtained from healthy subjects (CTRL, G1, I1, K1, M1, O1, Q1) and long-standing T1D individuals (T1D+ESRD, G2, I2, K2, M2, O2, Q2). Ultrastructural analysis scale bar: 2000 nm. Original histology magnification: 100X in G1-G2; 400X in I1-I2, K1-K2; 40X in O1-O2; 200X, in Q1-Q2. Scale bar 80 micron. H, J, L, N, P, R. Bar graphs reporting the measurement of crypts, the number of Ki67+ (MIB1+) cells, of neuroendocrine vesicles of nerve terminals (number of cases with >3 NE vesicles detected per nerve terminal), of 5HT+ and Aldh+ cells, and of EphB2+ expression (intensity score 0-5) in CTRL and long-standing T1D subjects (T1D+ESRD). n=20 CTRL and n=60 T1D+ESRD individuals were included in the evaluation. Data are expressed as mean ± standard error of the mean (SEM) unless differently reported. *p<0.01; **p<0.001; ***p<0.0001.
Abbreviations: GSRS, Gastrointestinal Symptom Rating Scale; T1D, type 1 diabetes; ESRD, end stage renal disease; CTRL, healthy subjects; H&E, hematoxylin and eosin; MIB1, antibody against Ki67; EphB2, Ephrin B receptor 2; Aldh, Aldehyde dehydrogenase; 5HT, serotonin; NE, neuroendocrine vesicles.