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Peripheral Immune Reprogramming Characterizes a Low C-Peptide Subgroup of Type 2 Diabetes: Transcriptomic Profiling
Yajing Xu1, Yiting Li1, Xiying Zeng1
1Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People's Republic of China.
Journal of Inflammation Research
|July 13, 2026
Summary
Type 2 diabetes with low C-peptide (T2DM-LowC) exhibits a distinct immune profile, characterized by higher systemic inflammation response index (SIRI). A three-gene signature from peripheral blood mononuclear cells (PBMCs) aids in identifying this T2DM subgroup.
Area of Science:
- Immunology
- Endocrinology
- Genetics
Background:
- Type 2 diabetes mellitus (T2DM) is a heterogeneous condition.
- A subgroup of T2DM patients with low C-peptide levels (T2DM-LowC) shows poorer glycemic control and unique therapeutic requirements.
- The peripheral immune characteristics and non-invasive markers for T2DM-LowC are not well-defined.
Purpose of the Study:
- To investigate the distinct peripheral immune profile associated with T2DM-LowC.
- To identify potential non-invasive markers for differentiating T2DM subgroups.
Main Methods:
- Propensity score-matched cross-sectional study comparing T2DM-LowC (n=109) and T2DM with preserved C-peptide (T2DM-PresC, n=109) groups.
- Exploratory transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) using differential expression, WGCNA, and CIBERSORTx.
- Validation of candidate genes in an independent cohort using RT-qPCR.
Main Results:
- T2DM-LowC patients had lower BMI and triglycerides, higher alkaline phosphatase, and elevated Systemic Inflammation Response Index (SIRI).
- PBMC analysis revealed reduced mast-cell signatures, increased resting NK and CD4 memory T-cell signatures, and a shift toward memory B cells.
- A three-gene panel (CSF2RB, NIBAN1, TLR1) effectively discriminated T2DM subgroups (AUC=0.903).
Conclusions:
- T2DM-LowC is associated with a distinct clinical and peripheral immune signature.
- Combining SIRI with a three-gene PBMC signature may offer a non-invasive method for identifying T2DM-LowC patients.
- Further validation in larger cohorts is warranted for these immune cell findings.
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