# Longitudinal monitoring of type 1 diabetes progression to disease onset

**Authors:** Jessica L. King, Jyotirmoy Roy, Russell R. Urie, Elizabeth Bealer, Kelly Crumley, Laila Rad, Scott A. Soleimanpour, Lonnie D. Shea

PMC · DOI: 10.1126/sciadv.adw8946 · 2026-01-28

## TL;DR

A new method using a subcutaneous scaffold detects type 1 diabetes progression before symptoms appear, offering earlier intervention opportunities.

## Contribution

A subcutaneous immunological niche enables early detection of T1D progression in a mouse model before glucose dysregulation.

## Key findings

- The scaffold identifies disease progressors 5 to 7 weeks before onset in a mouse model.
- The method distinguishes at-risk from non-risk groups at 6 weeks of age.
- Early disease detection is possible in a nonvital tissue distant from the pancreas.

## Abstract

Preventing autoimmune type 1 diabetes (T1D) necessitates improved monitoring for disease progression before symptom onset. Current diagnostic methods assess circulating autoantibodies, C-peptide levels, or dysglycemia, yet these approaches fail to identify β cell destruction preceding glucose dysregulation. Here, a subcutaneous microporous scaffold is used as an immunological niche (IN), which provides a nonvital accessible tissue reflecting many immune changes occurring in the pancreas. Sequencing analysis of the IN successfully delineates at-risk from nonrisk groups, as well as disease progressors from nonprogressors at 6 weeks of age in the nonobese diabetic mouse model. Within progressors, we identify disease 5 to 7 weeks before disease onset. Collectively, disease occurring in a poorly accessible site can be identified early by sampling a distant nonvital tissue, indicating the systemic nature of the disease and informing the timing of disease modifying therapies to halt or delay the progression of T1D.

Subcutaneous monitoring for type 1 diabetes identifies disease progressors from an at-risk group before symptom onset.

## Linked entities

- **Diseases:** type 1 diabetes (MONDO:0005147), T1D (MONDO:0005147)

## Full-text entities

- **Genes:** Gnas (GNAS complex locus) [NCBI Gene 14683] {aka 5530400H20Rik, A930027G11Rik, C130027O20Rik, GPSA, GSP, Galphas}, Zc3h12a (zinc finger CCCH type containing 12A) [NCBI Gene 230738] {aka MCPIP, MCPIP-1, Mcpip1, Reg1}, Lipm (lipase family member M) [NCBI Gene 78753] {aka 4632427C23Rik, Lipl3}, Dlx3 (distal-less homeobox 3) [NCBI Gene 13393] {aka Dlx-3}, Marco (macrophage receptor with collagenous structure) [NCBI Gene 17167] {aka Ly112, Scara2}, Padi3 (peptidyl arginine deiminase, type III) [NCBI Gene 18601] {aka Pad3, Pdi3, mKIAA4171}, Ccdc85b (coiled-coil domain containing 85B) [NCBI Gene 240514], Mgat2 (Mannosyl (alpha-1,6-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase) [NCBI Gene 43563] {aka CG7921, Dmel\CG7921, GlcNAc-TII, GlcNAcT2, MGAT, dMGAT2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Sh3gl3 (SH3-domain GRB2-like 3) [NCBI Gene 20408] {aka EEN-B2, SH3P13, Sh3d2c, Sh3d2c2}, Par2 (pulmonary adenoma resistance 2) [NCBI Gene 109447], Mgat2 (mannoside acetylglucosaminyltransferase 2) [NCBI Gene 217664] {aka CDGS2, GLCNACTII, GNT-II, GNT2}, Loricrin (loricrin cornified envelope precursor protein) [NCBI Gene 16939] {aka Lor}, Erdr1x (erythroid differentiation regulator 1 x) [NCBI Gene 170942] {aka Erdr1, Gm21887, Gm55594, edr}, Zfp760 (zinc finger protein 760) [NCBI Gene 240034] {aka 9430018I06}, Amd1 (S-adenosylmethionine decarboxylase 1) [NCBI Gene 11702] {aka AdoMetDC, Amd-1, SAMDC, SAMDC 1, adoMetDC1}, Rbfa (ribosome binding factor A) [NCBI Gene 68731] {aka 1110032A13Rik}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Dnase1 (deoxyribonuclease I) [NCBI Gene 13419] {aka DNaseI, Dnl1}, Adamts3 (ADAM metallopeptidase with thrombospondin type 1 motif 3) [NCBI Gene 330119] {aka 1100001H14Rik, 6330442E02Rik}
- **Diseases:** multiple sclerosis (MESH:D009103), inflammation (MESH:D007249), NOD (MESH:D020191), diabetes (MESH:D003920), insulin resistance (MESH:D007333), respiratory infection (MESH:D012141), glucose dysregulation (MESH:D018149), T1D (MESH:D003922), IN (MESH:D007154), cancer (MESH:D009369), type 2 diabetes (MESH:D003924), experimental autoimmune encephalomyelitis (MESH:D004681), autoimmune disease (MESH:D001327), stage 2 (MESH:D062706), hyperglycemia (MESH:D006943)
- **Chemicals:** Blood glucose (MESH:D001786), teplizumab (MESH:C502540), NaCl (MESH:D012965), isoflurane (MESH:D007530), water (MESH:D014867), C-peptide (MESH:D002096), ethanol (MESH:D000431), IN (-), isopentane (MESH:C067038), carprofen (MESH:C007005), TRIzol (MESH:C411644), lipid (MESH:D008055), Glucose (MESH:D005947), salt (MESH:D012492)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12851030/full.md

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Source: https://tomesphere.com/paper/PMC12851030