The report highlights that insulin-derived amyloidosis can mimic other injection-site reactions and should be considered when patients present with unexplained subcutaneous masses at insulin injection sites.
The patient, who has
type 1 diabetes mellitus (T1DM) diagnosed at age 5, noticed a new subcutaneous mass in the right lower quadrant of her abdomen. She also reported intermittent night sweats, chills, migrating paresthesias in her face and extremities, and joint pains in her ankles, knees, hips, and wrists. Her diabetes management included multiple daily subcutaneous insulin injections, primarily in the abdomen. A biopsy performed by her primary care physician revealed amyloidosis with strong Congo red staining.
Upon admission, her vital signs were normal. Examination confirmed a firm, nonfluctuant mass beneath the biopsy site, mild leg edema, and nonspecific motor and sensory deficits in the lower limbs. A neurologic work-up, including cerebrospinal fluid analysis, was unremarkable. Blood and urine tests to rule out systemic amyloidosis, including complete blood count, liver and kidney function tests, serum-free light chains, and protein electrophoresis, returned normal results. Imaging with CT scans showed a soft-tissue collection in the subcutaneous fat of the abdominal wall but no internal organ involvement. Echocardiography did not indicate amyloid deposits.
The patient was referred for surgical excision of the lesion, measuring 2 × 2 × 1.4 cm. Histopathology confirmed nodular-pattern cutaneous amyloidosis. Given the patient’s history of repeated insulin injections at the site and normal systemic evaluations, the amyloidosis was suspected to be insulin-derived. Mass spectrometry of the biopsy sample confirmed a peptide profile consistent with insulin-associated amyloid deposition.
Six months postoperatively, a small, superficial residual lesion was noted on ultrasonography, but the patient reported no further systemic symptoms and had avoided injecting insulin at the site.
Insulin-derived amyloidosis is a rare but increasingly recognized complication of repeated subcutaneous insulin injections. Clinically, it is difficult to distinguish from lipohypertrophy, the more common consequence of repeated injections, as both present as firm nodules. Unlike lipohypertrophy, insulin-derived amyloid deposits do not resolve after stopping injections at the site and can reduce insulin absorption and glycemic control. Histologically, they can resemble light chain amyloidosis, but mass spectrometry or immunohistochemistry can confirm the diagnosis and prevent unnecessary systemic investigations.
The case emphasizes the importance of clinician awareness of insulin-derived amyloidosis. Patients with persistent abdominal masses at injection sites should undergo imaging and biopsy for accurate diagnosis. Surgical excision is a viable option when lesions impair insulin absorption or for diagnostic confirmation. Rotating injection sites remains a key preventive measure.
“While the condition is benign and localized, early recognition helps avoid complications and unnecessary testing for systemic amyloidosis, improving patient care in diabetes management,” the authors concluded.
Reference: CMAJ 2025 October 27;197:E1184-7. doi: 10.1503/cmaj.241719
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