Introduction and Objective: South Asians (SA) have a higher risk of developing type 2 diabetes (T2D), with studies suggesting insulin insufficiency plays the major role. However, very little is known about pancreatic islet structure in this population. We studied pancreatic sections using multiplex immunohistochemistry (CODEX), enabling simultaneous imaging of dozens of protein markers within a single tissue section Methods: Pancreatic formalin-fixed paraffin-embedded sections from nine patients (age 18-60, 5M/4F, BMI 18.4-29.5, HbA1c 5.3-6.3 with 7.2 in one donor and 8.5% one donor) who underwent surgery at AIG Hyderabad, including four with adenocarcinoma, were stained using a 42-marker CODEX panel and H primarily Caucasian/African American) stained with the same panel. Results: SA donors showed greater acinar density, more immune cell infiltration around large ducts (assessed by CD45+ staining and HCD45+1.5±0.7%). SA pancreatic sections had lower islet density (3.8±0.6 vs 10.1±5.7/mm²), smaller mean islet area (968±370 vs 3,720±2,327 µm²), higher proportion of beta cells, and lower alpha-to-beta cell ratio. Co-expression analysis showed 12±2% of proinsulin+ cells lacked C-peptide, suggesting impaired proinsulin processing. Conclusion: SA pancreatic tissue showed distinct exocrine features, including less fat and more periductal inflammation. Islet cell composition differed from HPAP donors, with lower islet density, smaller islets, a higher beta cell fraction, and a lower alpha-to-beta ratio. Multiplexed imaging suggested impaired proinsulin processing. This raises the possibility of lower beta cell mass in the SA population. Disclosure A. Eskaros: None. S. Pinninti: None. F. Feng: None. R. Jenkins: None. P.R. Somvanshi: None. L. Staimez: None. J.J. Wright: None. M. Brissova: None. K. Narayan: None. M. Sasikala: None. A.C. Powers: None. Funding DBT / Wellcome Trust India Alliance
Pandey et al. (Fri,) studied this question.