Evidence map›Paper›PMID 42283639›Full record

ArticleDiabetes2026

Type 2 Diabetes Reduces IFN-α2 and Compromises Antiviral Defense: Evidence From Mendelian Randomization and H1N1-Infected Diabetic Mice.

Siye Lyu, Jiali Wu, Weihui Ma, Liping Sun, Sihui Xing, Haiyang Zhang, Fengyan Shao, Mingquan Li, Yilong Zhu, Xiaomiao Xiong and 1 more

Abstract read
In one paragraph

Article in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Siye LyuKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Jiali WuKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Weihui MaKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Liping SunChangchun University of Chinese Medicine, Changchun, China.
Sihui XingKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Haiyang ZhangKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Fengyan ShaoKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Mingquan LiChangchun University of Chinese Medicine, Changchun, China.
Yilong ZhuKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.
Xiaomiao XiongDepartment of Respiratory and Critical Care Medicine, Second Medical Center of the People's Liberation Army General Hospital, Beijing, China.ORCID 0009-0007-5769-8306
Jicheng HanKey Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China.ORCID 0009-0003-1126-305X

Funding

National Natural Science Foundation of China 82405318the Science and Technology Development Plan Project of Jilin Province YDZJ202501ZYTS214
6 · The paper itself

Abstract

Type 2 diabetes (T2D) impairs antiviral immunity; however, the causal link between T2D and interferon-α2 (IFN-α2) deficiency remains unclear. This study used genome-wide association study-based Mendelian randomization (MR) to investigate this relationship and validated the findings in an H1N1-infected diabetic mouse model. MR analysis of 26 single nucleotide polymorphisms showed a significant negative association between T2D and IFN-α2 levels (inverse variance weighted odds ratio 0.667; P = 0.000116) without heterogeneity or pleiotropy. In vivo experiments confirmed that db/db mice exhibited more severe H1N1-induced lung injury, higher viral loads, and lower survival rates compared with nondiabetic controls. However, exogenous IFN-α2 treatment significantly reversed these pathologic outcomes. Inflammatory cytokine profiling showed that IFN-α2 downregulated 21 elevated cytokines and restored Fas ligand levels in lung tissue. Mechanistically, Western blotting demonstrated that IFN-α2 inhibited the phosphorylation of JAK1/2 and STAT3, thereby suppressing excessive inflammation. In conclusion, our findings indicate that T2D leads to IFN-α2 deficiency, contributing to susceptibility to viral infection. Supplementation with IFN-α2 effectively attenuated virus-induced lung injury by inhibiting JAK/STAT3 signaling and cytokine storms, positioning IFN-α2 supplementation as a promising therapeutic strategy for managing influenza complications in patients with diabetes. ARTICLE HIGHLIGHTS: Type 2 diabetes (T2D) is linked to impaired antiviral immunity, but whether it drives interferon-α2 (IFN-α2) deficiency remains unknown. We asked whether T2D causally suppresses IFN-α2 levels and whether exogenous supplementation could rescue host defense mechanisms against influenza infection. By integrating genetic analysis with an H1N1-infected diabetic mouse model, we show that T2D genetically lowers IFN-α2 and that treatment reverses lung injury by inhibiting JAK/STAT3-mediated hyperinflammation. Our study positions IFN-α2 supplementation as a promising therapeutic strategy to prevent severe viral pneumonia in patients with T2D.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Influenza A Virus, H1N1 SubtypeInterferon-alphaOrthomyxoviridae InfectionsAnimalsGenome-Wide Association StudyMiceMice, Inbred C57BLPolymorphism, Single NucleotideInterferon-alpha

Identifiers

PMID42283639
PMCPMC13381667

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.