Diabetes and mucormycosis

Abstract

Mucormycosis is an invasive, opportunistic, and rapidly progressing fungal infection caused by fungi of the order Mucorales. Although infrequent, it continues to be associated with high morbidity and mortality, particularly in people with poorly controlled diabetes mellitus, where hyperglycemia and, especially, diabetic ketoacidosis are the main predisposing factors. The COVID-19 pandemic highlighted this association once again, with an unprecedented increase in cases of rhino-orbito-cerebral mucormycosis observed in diabetic patients exposed to corticosteroids, reinforcing the importance of adequate metabolic control as a preventive strategy.

From a pathophysiological perspective, sustained hyperglycemia alters the function of neutrophils and macrophages, while metabolic acidosis increases the availability of free iron, favoring the growth of Mucorales. Furthermore, overexpression of the GRP78 receptor under hyperglycemic conditions facilitates endothelial invasion, promoting the fungus's characteristic angioinvasion, which is responsible for thrombosis, tissue necrosis, and rapid dissemination. These mechanisms explain the fulminant progression of the disease and the need to maintain a high index of clinical suspicion in diabetic patients presenting with sinusitis, facial pain, periorbital edema, ophthalmoplegia, or necrotic lesions.

The prognosis depends primarily on early recognition and immediate initiation of treatment. Current management is based on four pillars: correction of metabolic abnormalities, aggressive surgical debridement, early administration of liposomal amphotericin B as first-line treatment, and, when appropriate, sequential therapy with isavuconazole or posaconazole. Several studies have demonstrated that delayed treatment is associated with a significant increase in mortality, which remains high in disseminated forms.

For diabetologists, mucormycosis represents a rare but potentially devastating complication. Early identification of at-risk patients, optimization of glycemic control, judicious use of corticosteroids, and coordination with infectious disease specialists, otolaryngologists, ophthalmologists, and surgeons are essential strategies for improving prognosis. Currently, the challenge lies not only in treating the infection but also in recognizing it promptly before angioinvasion and tissue necrosis lead to irreversible damage.