PROPOSED ACTION ITEM FOR BIG PHARMA
Prt 1
Localized insulin-derived amyloidosis (LIDA) is an iatrogenic disease derived from subcutaneous insulin formulations. The amyloid fibril protein is classified as amyloid insulin type, AIns, and the amyloid precursor protein is also identified as insulin.
The first account of LIDA in a human was in 1983. Since that time, many patient case reports have been published as well as review articles and laboratory analyses. In 1987, porcine insulin became the first foreign protein to become identified in human amyloid fibrils, a case that was discovered in a person with Type 1 diabetes where localized amyloidosis was found at the sites of insulin injection. Interestingly, this finding also established exogenous insulin as the first official case of iatrogenic amyloidosis. In the 1980's localized insulin-derived amyloidosis was inducted into the official nomenclature guidelines maintained by the International Society of Amyloidosis Nomenclature Committee. In a more recent study that was approved by the Mayo Foundation Institutional Review Board, localized insulin-derived amyloidosis was discovered in 50 people between January 2010 and May 2013—hardly suggestive of being an uncommon or rare occurrence.
Remarkably, the exact pathogenesis of LIDA remains unclear among the few that are aware of its existence within the medical and scientific communities.
Subcutaneous insulin formulations have historically been known for their poor stability. Rapid acting analogs, a form of subcutaneous insulin, have modified insulin's amino acid sequences to prevent the self assembly of insulin into hexamers and to favorably promote dissociation into monomers. Numerous additives are also included in subcutaneous insulin formulations, some of them known to be toxic: m-cresol and phenol, which could potentially in facilitating aggregation and/or denaturation of the insulin in the formulation. Another possible contributor for causing LIDA is the slow, erratic absorption that is common for subcutaneous insulins
Currently, this adverse reaction is not disclosed on insulin labels or by the FDA or ADA, despite it being a known complication since the 1980's.
Lack of awareness prevents people with diabetes and medical and scientific communities from knowing about LIDA in the first place. Knowing the clinical characteristics of LIDA, potential side effects and expected outcomes are not well established since LIDA has yet to be disclosed of to the medical community.
When considering the dearth of information on LIDA compared to the quantity of occurrences, the plausibility of LIDA being an uncommon or rare occurrence is highly unlikely.
LIDA is actually commonly misdiagnosed as lipohypertrophy, and goes under-reported due to a lack of label warning and consequently of awareness, education, diagnostic equipment and trained clinicians.
Diagnosis of AIns requires histopathological investigation, where Congo red staining is considered the gold standard for amyloid identification. Subtype identification is needed to identify the amyloid protein and many diagnostic methods can be used for this, such as: immunohistochemistry, Western blotting, mass spectrometry, immune-electron microscopy or amino acid sequence analysis (preferred).
Treatment for LIDA is surgical excision of the amyloid mass or the complete avoidance of insulin injections at or in close proximity to the mass. However, recent findings in a patient with diabetes who developed LIDA has revealed that the amyloid mass is capable of continued growth despite complete avoidance of insulin injections at the site of the mass.
It is highly plausible that LIDA is commonly misdiagnosed as lipohypertrophy due to the lack of awareness. diagnostic equipment and trained clinicians.
There is zero mention of LIDA on subcutaneous insulin labels, FDA website, ADA nor the Standards of Care. Awareness has been suppressed, attention manipulated and diverted to avoid disclosure of dangerous localized insulin-derived amyloidosis required by US law.
Evidence:
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Localized Amyloidosis at the Site of Repeated Insulin Injection in a Diabetic Patient
www.jstage.jst.go.jp/article/internalmedicine/49/5/49_5_397/_pdf
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Progressive insulin-derived amyloidosis in a patient with type 2 diabetes
www.ncbi.nlm.nih.gov/pmc/articles/PMC5095519/
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Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series
www.amjmed.com/article/S0002-9343(14)00035-7/fulltext
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Localized insulin-derived amyloidosis: A potential pitfall in the diagnosis of systemic amyloidosis by fat aspirate
onlinelibrary.wiley.com/doi/10.1002/ajh.23334/full
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Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report