Localized Amyloidosis at the Site of Repeated Insulin Injection in a Patient With Type 2 Diabetes

Okamura, Shintaro; Hayashino, Yasuaki; Kore-Eda, Satoshi; Tsujii, Satoru

doi:10.2337/dc13-1651

Cited by 58 publications

(39 citation statements)

References 3 publications

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“…Insulin is usually injected into the body, although this method is not suitable for all diabetes patients. Furthermore, insulin amyloidosis has frequently been found at the site of repeated insulin injections in diabetic patients . Insulin pumps eliminate the need for daily injections and assist in the delivery of precise amounts of insulin .…”

Section: Methodsmentioning

confidence: 99%

Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity

Rajan

Suzuki

Matsumura

2018

Macromolecular Bioscience

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The synthesis of a zwitterionic polymer, poly-sulfobetaine (poly-SPB), which shows remarkable efficiency in the suppression of insulin aggregation is described. Hydrophobic modification of the polymer results in almost complete inhibition at very low polymer concentrations. Further studies reveal that these polymers facilitate the complete retention of insulin's secondary structure, which is otherwise lost after incubation. Refolding studies show that addition of polymers to preaggregated insulin sample leads to the refolding of denatured insulin, indicating their potential to facilitate the refolding of the denatured proteins. In addition, 2D NMR studies show that the presence of hydrophobic poly-SPB alters the hydrophobic environment of insulin, which may suppress hydrophobic interactions that lead to aggregation. These results indicate the enormous potential of these polymers for suppressing insulin aggregation and provide significant insight into the complex mechanism of insulin protection by zwitterionic polymers.

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Section: Methodsmentioning

confidence: 99%

Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity

Rajan

Suzuki

Matsumura

2018

Macromolecular Bioscience

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“…Similar to what may be seen with lipohypertrophy, AIns can result in inconsistent insulin delivery due to alterations in insulin absorption, therefore negatively affecting patient care and glycemic control (5). AIns may also be associated with insulin resistance due to local inflammation and subsequent insulin breakdown (6).…”

Section: Discussionmentioning

confidence: 96%

An Atypical Presentation of Insulin Amyloidosis: An Uncommon but Important Complication of Insulin Therapy

Sullivan

Gedik

Haddady

2018

AACE Clinical Case Reports

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Objective:To describe a case of insulin amyloidosis that highlights an uncommon but significant complication of subcutaneous insulin therapy.Methods: We review the case of a patient with type 2 diabetes mellitus on long-standing insulin therapy with insulin amyloid deposits found at the insulin injection sites and the possible clinical complications associated with this condition.Results: A fat-pad aspirate of the abdomen, which was performed for the evaluation of worsening renal function, was positive for Congo red staining. Further subtype analysis via liquid chromatography in tandem with mass spectrometry revealed a peptide profile of insulin-derived amyloid deposition.Conclusions: Insulin amyloid is a less common but important complication of insulin therapy. Often patients will present with dermatologic changes at the site of insulin amyloid deposition, however some have faint (as in our patient) or no physical changes on exam. It is important for clinicians to be aware of this condition, not only to educate patients on proper insulin administration, but also to be aware of conditions which can influence insulin pharmacokinetics. (AACE Clinical Case Rep. 2018;4:e80-e83) Abbreviation: AIns = insulin-derived amyloid deposition

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“…Nodular AIns lesions are more firm and solid than those of lipohypertrophy, and are unlikely to regress after injection site rotation. If a mass, which has appeared at the site of insulin injections, does not disappear after its cessation, a biopsy should be performed . Although on clinical grounds the differential diagnosis between lipohypertrophy and nodular AIns tumor is almost impossible, nodular AIns tumors and lipohypertrophy show completely different findings from a histopathologic perspective.…”

Section: Discussionmentioning

confidence: 99%

“…If a mass, which has appeared at the site of insulin injections, does not disappear after its cessation, a biopsy should be performed. 16 Although on clinical grounds the differential diagnosis between lipohypertrophy and nodular AIns tumor is almost impossible, nodular AIns tumors and lipohypertrophy show completely different findings from a histopathologic perspective. While lipohypertrophy shows hypertrophic adipocytes, because of the lipogenic effect of insulin, nodular AIns tumor presents deposits of homogeneous eosinophilic fractured material, which occupies dermis and subcutis and is frequently surrounded by multinucleated giant cells.…”

Section: Discussionmentioning

confidence: 99%

Nodular amyloidosis at the sites of insulin injections

et al. 2015

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Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long-standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti-human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast-acting and slow-acting insulins at the same injection sites. Our second case showed nodular insulin-derived amyloid tumors only at the sites where exclusively fast-acting insulin was injected, which supports the notion that fast-acting insulin may also be the cause of this disorder. Insulin-derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.

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Localized Amyloidosis at the Site of Repeated Insulin Injection in a Patient With Type 2 Diabetes

Cited by 58 publications

References 3 publications

Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity

Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity

An Atypical Presentation of Insulin Amyloidosis: An Uncommon but Important Complication of Insulin Therapy

Nodular amyloidosis at the sites of insulin injections

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