Imaging characteristics of subcutaneous amyloid deposits in diabetic patients: the “insulin ball”

Abstract

Subcutaneous amyloid deposits which cause insulin resistance are typically ill-defined and heterogeneous hypovascular subcutaneous nodules with irregular margins on imaging that correspond to insulin injection sites. It is also characteristic that T2WI shows low intensity compared with fat on MRI, reflective of the amyloid content.

Extreme Adhesion Activity of Amyloid Fibrils Induces Subcutaneous Insulin Resistance

“…We shortened the preparation period and increased the size of the mass so that we could perform insulin tolerance tests by administering much higher doses (1.2 mg/day) of insulin amyloid. Our mice with quickly formed insulin-derived amyloidomas exhibited pathological features similar to those of patients (13)(14)(15)18,24,30): reactive inflammation and foreign body reactions with various types of cells, including plasma cells, macrophages, lymphocytes, and multinucleated giant cells in and around the amyloid deposits ( Fig. 3).…”

“…However, several unanswered questions remain, including the mechanism that initiates the first amyloid fibril formation in particular patients. Fibrosis, inflammation, and insulin fragmentation at an injection site may be involved in amyloid fibril formation (5,30), but additional research is required to elucidate the mechanism of initiation of insulin-derived amyloidosis. Regression of an insulin-derived amyloidoma reportedly requires long time periods (5,7), whereas lipohypertrophy usually regresses soon after the insulin injection site is changed, but the precise rate and mechanism of insulin amyloid degradation have not been determined.…”

Nanomaterials to avoid and destroy protein aggregates

“…As described above, amyloid plaques formation is involved in neurodegenerative diseases, though similar processes have been described in diabetes mellitus, especially in type 2 diabetes. Repeated administrations of insulin can lead to the formation of subcutaneous amyloid deposits at the injection site, leading to poor glycemic control and insulin resistance [67,68]. In literature, the inhibition of insulin fibrillation has been described, in a concentration-dependent manner with carbon dots [69] and with silicon nanoparticles [70].…”

Insulin Fibril Formation Caused by Mechanical Shock and Cavitation

“…13,14 Fibril deposits at sites of repeated insulin injections may grow to be disfiguring masses several centimeters in diameter. 15 Insulin fibrillation is a nucleationdependent process and proposed to occur via partial unfolding of a monomeric or dimeric intermediate. 16 In the case of insulin deposition disease, it is unclear what triggers the presumed nucleation event that leads to the growing masses of fibrillar insulin deposits, but the preferential occurrence of fibrillar insulin deposits at repeated sites of injection opens the possibility that the fibril nuclei may form in vitro prior to injection in patients and continue to grow in vivo with repeated insulin injections.…”

“…Insulin-derived amyloidosis is a rare yet significant complication of insulin therapy. − It is characterized by deposition of insoluble insulin amyloids in tissues and organs that can lead to life-threatening organ failure . Amyloidosis at insulin injection sites causes impairment in insulin absorption that leads to difficulties in glucose regulation, and insulin amyloids exhibit toxicity and may cause necrosis in the surrounding tissue. , Fibril deposits at sites of repeated insulin injections may grow to be disfiguring masses several centimeters in diameter . Insulin fibrillation is a nucleation-dependent process and proposed to occur via partial unfolding of a monomeric or dimeric intermediate .…”