The insulin ball

Nagase, Terumasa; Katsura, Yoshiya; Iwaki, Yoshiki; Nemoto, Kenji; Sekine, Hidenori; Miwa, Kazuhiro; T, Ohi; Kou, Keni; Iwaya, Keiichi; Noritake, Masayuki; Matsuoka, Takeshi

doi:10.1016/s0140-6736(09)60041-6

Cited by 61 publications

(68 citation statements)

References 4 publications

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“…Subcutaneous AIns amyloidosis is a well-recognized but infrequent complication of subcutaneous insulin injections for the management of insulin-dependent diabetes mellitus. 34,35 Patients often present with masses in the areas of repeated insulin injection, and the insulin amyloid remains localized to these sites. The only significant clinical consequence of such a diagnosis appears to be increasing insulin resistance due to poor diffusion of the injected insulin through the amyloid mass if the area continues to be used for repeated insulin injections.…”

mentioning

confidence: 99%

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Vrana¹,

Theis²,

Dasari³

et al. 2014

Haematologica

143

111

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Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis.Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics ABSTRACT Subcutaneous fat aspiration for diagnosis of systemic amyloidosisSpecimens were obtained, stained with Congo red and interpreted according to previously established protocols described elsewhere.5 For the validation cohort one half of each specimen was used to make a smear and stained with Congo red. The other half, irrespective of whether the smear was positive for amyloid by Congo red, was processed for MS-based proteomic analysis. For the clinical cohort, one half of each specimen was used to make a smear and stained with Congo red. The other half was processed for MS-based proteomic analysis only if the first half stained positive for amyloidosis, as required by the established clinical practice and test validation criteria. Mass spectrometry-based proteomic analysis of subcutaneous fat aspiratesThe SFA specimens were processed for MS analysis using a modification of a previously established protocol.26 Briefly, the aspirate was solubilized and digested in trypsin and used for protein identification by nano-flow liquid chromatography electrospray tandem MS.9 Peptide spectra present in the raw data files were matched against a composite protein sequence database using three different search engines (Sequest Measurement of serum immunoglobulin free light chainsSerum immunoglobulin ...

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mentioning

confidence: 99%

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Vrana¹,

Theis²,

Dasari³

et al. 2014

Haematologica

143

111

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“…Insulin-derived amyloidosis, also known as ‘insulin ball’,[1] is a rare skin-related complication of insulin therapy. Insulin injections at the same site may be a risk factor of amyloidosis formation,[1–7] but the mechanism underlying insulin-derived amyloidosis formation is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin injections at the same site may be a risk factor of amyloidosis formation,[1–7] but the mechanism underlying insulin-derived amyloidosis formation is still unknown. The differential diagnoses of local site reactions in patients on insulin therapy include lipohypertrophy, which has many symptoms in common with insulin-derived amyloidosis.…”

Section: Discussionmentioning

confidence: 99%

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Progressive insulin-derived amyloidosis in a patient with type 2 diabetes

Shiba

Kitazawa

2016

Case Reports in Plastic Surgery and Hand Surgery

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“…There was no evidence of inflammation. Rather, the histopathologic pattern was like that of fat tissue undergoing starvation, except for the amyloid deposition, that is conglomerates of denaturated exogenous insulin or insulin analog [7]. …”

Section: Introductionmentioning

confidence: 99%

Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

Chantelau¹,

Prätor²,

Prätor³

2014

J Med Case Reports

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IntroductionLocalized involutional lipoatrophy of subcutaneous adipose tissue may develop due to subcutaneous injection of pharmaceutical preparations. The pathogenesis of this adverse drug reaction is unknown. The progression of localized involutional lipoatrophy ceases and occasionally it resolves after withdrawing the inducing agent. In case of localized involutional lipoatrophy due to subcutaneous insulin therapy, low-dose systemic corticosteroids may be curative despite ongoing insulin administration.Case presentationWe report a recurrence of insulin-induced localized involutional lipoatrophy at the abdominal wall in a 57-year-old Caucasian woman with type-1 diabetes on continuous subcutaneous insulin infusion. The first episode of insulin-induced localized involutional lipoatrophy two years previously had been cured by oral prednisone. The recurrence was treated immediately with 10mg prednisone once daily for five months, and was cured thereafter. The insulin analog preparation (Humalog™) and the insulin pump equipment (Accu-Chek Spirit™) applied were the same during both episodes. Both episodes were preceded by a temporary disturbance of the immune balance (the first episode by vaccination, the second episode through shingles).ConclusionsThis case confirms that insulin-induced localized involutional lipoatrophy in type-1 diabetes can occur again, and can be cured by systemic corticosteroids. We suggest that temporary disturbance of the immune balance may trigger this transitory idiosyncratic reaction in a susceptible individual.

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The insulin ball

Cited by 61 publications

References 4 publications

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Progressive insulin-derived amyloidosis in a patient with type 2 diabetes

Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

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