What does this research mean for the field?

Hyperglycemia exacerbates Chikungunya virus-induced joint inflammation, tissue damage, and nociceptive sensitivity independently of viral load, driven instead by the diabetic metabolic milieu. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research investigates how diabetes mellitus impacts the severity of chikungunya virus infection.

May 29, 2026Open Access

Hyperglycemia Enhances Chikungunya Virus-Induced Tissue Damage: Histopathological Evidence from a Murine Model

Key Points

This research investigates how diabetes mellitus impacts the severity of chikungunya virus infection.
Established an in vivo murine model using streptozotocin-induced diabetic C57BL/6 mice.
Infected diabetic and normoglycemic mice with chikungunya virus and assessed histopathological outcomes.
Evaluated serum markers of muscle and hepatic injury, including creatine kinase and alanine aminotransferase.
Diabetic mice exhibited significant joint inflammation and nociceptive sensitivity compared to normoglycemic counterparts.
Elevated serum levels of creatine kinase and alanine aminotransferase indicated increased muscle and liver injury in diabetic mice.
Histopathological analyses revealed intensified tissue damage, including chondrocyte depletion and osteocyte necrosis, in hyperglycemic animals.

Abstract

Chikungunya fever (CHIKF) is a re-emerging viral disease characterized by acute systemic manifestations and debilitating musculoskeletal symptoms that can persist after viral clearance. Although typically self-limiting in healthy individuals, clinical outcomes are significantly worsened in patients with pre-existing comorbidities, particularly diabetes mellitus (DM). Epidemiological data links DM to heightened CHIKF severity and a greater risk of developing chronic arthropathy, yet the mechanism underpinning this association remains poorly understood. In this study, we established an in vivo streptozotocin (STZ)-induced diabetic C57BL/6 mice as a model to investigate the impact of DM on CHIKV pathogenesis. STZ induces selective pancreatic β-cell destruction and persistent hyperglycemia. Diabetic animals infected with CHIKV exhibited aggravated joint inflammation, increased nociceptive sensitivity, and elevated serum markers of muscle and hepatic injury, including creatine kinase (CK) and alanine aminotransferase (ALT) compared to normoglycemic infected animals. Histopathological analyses revealed that CHIKV infection alone disrupted joint architecture and initiate degenerative alterations. However, in hyperglycemic mice, CHIKV-induced lesions were markedly intensified, with pronounced inflammatory infiltrates, chondrocyte depletion, osteocyte necrosis, and fibrotic remodeling, closely resembling osteoarthritic damage. These aggravated histopathological outcomes were not associated with increased CHIKV load, but rather to the diabetic metabolic milieu. These results offer a plausible mechanistic explanation for the poorest CHIKF outcomes observed in diabetic patients. Thus, this model provides a valuable platform for exploring the molecular drivers of CHIKF severity and chronicity, especially among DM patients, as well as for development of pharmacological tools to mitigate CHIKV-associated complications in metabolically vulnerable populations.

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