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. As it would be, in the the 1980's localized insulin-derived amyloidosis was inducted into the offical amyloid protein and amyloidosis nominclature guidelines established and 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.

BIG PHARMA Prt 2

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 place for subcutaneous insulins. The insulin solution is injected into the hypodermis layer of the skin, which unfortunately is an excellent environment for suppressing drug absorption while inducing an inflammatory response. Ironically, macrophages are abound in this layer of the skin. Frequently rotating insulin injection sites is also crucial to avoid aggregation of insulin and deposition of insulin amyloids. The most significant contributor however is the is lack of awareness. 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.

There is zero mention of LIDA in subcutaneous insulin labels, FDA website, ADA nor the Standards of Care. Disclosing of localized insulin-derived amyloidosis has been deliberately withheld. The companies that own subcutaneous insulins are required by law to be disclose this information to the FDA, patients, providers, and the public.

Sauce:

1. 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

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

www. ncbi.nlm.nih.gov/pmc/articles/PMC5095519/

1. Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series www.amjmed.com/article/S0002-9343(14)00035-7/fulltext

1. 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

1. Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report

www.humanpathol.com/article/S0046-8177(09)00167-1/abstract

1. Cutaneous amyloidosis at the site of insulin injection with coexistence of acanthosis nigricans www.ijpmonline.org/article.asp?issn=0377-4929;year=2014;volume=57;issue=1;spage=127;epage=129;aulast=Nandeesh

1. Insulin Derived Amyloidosis

www.ncbi.nlm.nih.gov/pmc/articles/PMC4287767/

1. Ultrasonography Improves Glycemic Control by Detecting Insulin-Derived Localized Amyloidosis

www.umbjournal.org/article/S0301-5629(17)30279-X/pdf

1. A Case of Insulin Resistance Secondary to Insulin Induced Localized Cutaneous Amyloidosis.

www.bloodjournal.org/content/114/22/4908?sso-checked=true

1. Amyloidoma secondary to insulin injection: Cytologic diagnosis and pitfalls

www.ncbi.nlm.nih.gov/pmc/articles/PMC4527044/

1. Localized insulin amyloidosis with use of a concentrated insulin: a potential complication

onlinelibrary.wiley.com/doi/10.1111/dme.13137/abstract

1. Nodular amyloidosis at the sites of insulin injections

onlinelibrary.wiley.com/doi/10.1111/cup.12501/abstract

1. Current insight in the localized insulin-derived amyloidosis (LIDA): clinico-pathological characteristics and differential diagnosis www.sciencedirect.com/science/article/pii/S0344033817308750?via%3Dihub

1. A Case of Type 1 Diabetes Mellitus with Marked Poor Glycemic Control caused by Insulin-derived Amyloidosis at the Site of Repeated Insulin Injections

www.jstage.jst.go.jp/article/tonyobyo/58/1/58_34/_article

1. Coexistence of insulin-derived amyloidosis and an underlying acanthosis nigricans-like lesion at the site of insulin injection onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.2012.04373.x/abstract