Why 100-Years After the Discovery of Insulin and the Appearance of Insulin-Induced Lipodystrophy: Are We Still Struggling with this Nasty Complication?
DOI:
https://doi.org/10.17140/DROJ-8-156Keywords:
Diabetes; Insulin; Injection technique, Lipoatrophy; Lipohypertrophy;', Education; Rehabilitation.Abstract
Since a century ago, insulin extracted from the animal pancreas has been used for therapeutic purposes. Lipoatrophy (LA) lesions
came up first due to the impurities of preparations. However, as technology has progressed, we have had more purified insulin preparations
available, now reduced to less than 5%. The 95% of local complications was represented by lipohypertrophy (LH), due to
the recourse to narrow areas of skin, reuse of the same needle, injection of cold insulin. The average frequency of LH in the world
is 47%, with peaks of 75%, reflecting the inappropriate educational activity of the diabetic teams. In this brief review, the causes of
this failure are described, and feasible rehabilitative solutions are proposed.
References
Paulesco NC, Recherche sur le rôle du pancréas dans l’assimilation nutritive. [In: French]. Archives Internationales de Physi-ologie. 1921; 17(31): 85-109.
Lestradet H. Le 75e anniversaire de la découverte de l'insuline. Diabetes & Metabolism. 1997; 23(1): 112. doi : DM-02-1997-23-1- 1262-3636-101019-ART71
STORIA DEL DIABETE - La cura con l’insulina. [In: Italian]. http://www.museodeldiabete.com/storia14.htm#top. Accessed March 28, 2022.
de Leiva A, Brugués E, e de Leiva-Pérez A. The discovery of insulin: Continued controversies after ninety years. Endocrinol Nutr. 2011; 58(9): 449-456. doi: 10.1016/j.endoen.2011.10.001
Priesel R, Wagner R. Üeber lokade lipodystrophie nach insulin-injektionen. [In: German]. Zeitschrift fűr Kinderheilkunde. Z. Kinder-Heilk. 1928; 46: 453-456. doi: 10.1007/BF02248506
Fischer FE. The frequency of atrophy of the subcutaneous fat following the injection of insulin. Am J Dis Child. 1929; 38(4): 715-720. doi: 10.1001/archpedi.1929.01930100035003
Depisch F. Ueber lokale lipodystrophie bei lange zeit mit insu-lin behandelten diabetes. Klin Wochenschr. 1926; 5: 1965-1966. doi: 10.1007/BF01710208
Barborka CJ. Fatty atrophy from injections of insulin. JAMA. 1926; 87: 1646-1647. doi: 10.1001/jama.1926.92680200003012c
Davison RA. Absorption of subcutaneous fat deposits at site of repeated insulin injections. Cal West Med. 1927; 26(2): 210-212.
Mentzer SH, Dubray ES. Fatty atrophy from injections of insulin. Cal West Med. 1927; 26(2): 212.
Berard L, Desrochers F, Husband A, MacNeill G, Roscoe B. FIT Forum for Injection Technique Canada Recommendations for Best Practice in Injection Technique 2012. https://www. bd.com/resource.aspx?IDX=25063. Accessed March 28, 2022.
Rabinowitch IM. Atrophy of subcutaneous fat following in-sulin injections. Can Med Assoc J. 1928; 18(5): 560-561.
Carmichael EA, Graham G. Local fat atrophy following in-sulin injections. The Lancet. 1928: 214: 601. doi: 10.1016/S0140- 6736(00)96744-8
Chapman PD. A letter. The Lancet. 1928; 214: 674.
Blanco M, Hernández MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013; 39: 445-453. doi: 10.1016/j. diabet.2013.05.006
Gentile S, Agrusta M, Guarino G, et al. Metabolic conse-quence of incorrect insulin administration techniques in ag-ing subjects with diabetes. Acta Diabetol. 2011; 48: 121-125. doi: 10.1007/s00592-009-0172-x
Gentile S, Grassi G, Armentano V, et al. AMD-OSDI consen-sus on injection techniques for people with diabetes mellitus. Med Clin Rev. 2016, 2: 3. doi: 10.21767/2471-299X.1000034
Frid AH, Kreugel G, Grassi G, et al. New insulin delivery recommendations. Mayo Clin Proc. 2016; 91: 1231-1255. doi: 10.1016/j.mayocp.2016.06.010
Gentile S, Strollo F, Guarino G, et al. Why are so huge differ-ences reported in the occurrence rate of skin lipohypertrophy? Does it depend on method defects or on lack of interest? Diabetes Metab Syndr. 2019; 13(1): 682-686. doi: 10.1016/j.dsx.2018.11.042
Gentile S, Strollo F, Corte TD, Marino G, Guarino G. Insulin related lipodystrophic lesions and hypoglycemia: Double stan-dards? Diabetes Metab Syndr. 2018; 12(5): 813-818. doi: 10.1016/j. dsx.2018.04.023
Gentile S, Guarino G, Giancaterini A, Guida P, Strollo F, AMD-OSDI Italian Injection Technique Study Group. A suitable palpation technique allows to identify skin lipohypertrophic le-sions in insulin-treated people with diabetes. Springerplus. 2016; 5: 563. doi: 10.1186/s40064-016-1978-y
Gentile S, Strollo F, Guarino G, et al. Factors hindering correct identification of unapparent lipohypertrophy. J Diabetes Metab Dis-ord Control. 2016; 3(2): 42-47. doi: 10.15406/jdmdc. 2016.03.00065
Gentile S, Guarino G, Strollo F. A cry of pain for painless insulin lipohypertrophy. J Diabet Res Rev Rep. 2020; 2(1): 1-2. doi: 10.47363/JDRR/2020(2)102
Deng N, Zhang X, Zhao F, Wang Y, He H. Prevalence of lipohypertrophy in insulin-treated diabetes patients: A systematic review and meta-analysis. J Diabetes Investig. 2017; 9: 536-543. doi: 10.1111/jdi.12742
Heinemann L, Nguyen T, Bailey TS, et al. Needle technology for insulin administration: A century of innovation. J Diabetes Sci Tech-nol. 2021; 19322968211059564. doi: 10.1177/19322968211059564
De Berardis G, Scardapane M, Lucisano G, et al. Ef-ficacy, safety and acceptability of the new pen needle 34G × 3.5 mm: A crossover randomized non-inferiority trial; AGO 02 study. Curr Med Res Opin. 2018; 34(9): 1699-1704. doi: 10.1080/03007995.2018.1491396
SID Document. Gli aghi per penna insulina e altri an-28 Gentile S, et al ti-iperglicemici iniettivi. 2019. https://www.siditalia.it/ clinica/linee-guida-societari/send/80-linee-guida-docu-menti-societari/4848-2019-aggiornamento-gli-aghi-per-penna-insulina-e-altri-anti-iperglicemici-iniettivi. Accessed March 28, 2022.
Improta MR, Strollo F, Gentile S. Lessons learned from an unusual case of severe hypoglycemia. Diabetes Metab Syndr: Clin Res Rev. 2019; 13(2): 1237-1239. doi: 10.1016/j. dsx.2019.01.033
Gentile S, Strollo F, Corte TD, Marino G, Guarino G. Skin complications of insulin injections: A case presentation and a possible explanation of hypoglycaemia. Diabetes Res Clin Pract. 2018; 138: 284-287. doi: 10.1016/ j.diabres.2018.02.005
Gentile S, Guarino G, Strollo F. How to treat improper insulin injection-related lipohypertrophy: A 3-year follow-up of a mon-ster case and an update on treatment. Diabetes Res Clin Pract. 2021; 171: 108534. doi: 10.1016/j.diabres.2020.108534
Strollo F, Guarino G, Armentano V, et al on behalf of AMD-OSDI Italian Study Group on Injection Techniques. Unexplained hypoglycaemia and large glycaemic variability: Skin lipohypertro-phy as a predictive sign. Diabetes Res Open J. 2016; 2(1): 24-32. doi: 10.17140/DROJ-2
Gentile S. Strollo F, De Rosa N, Injection-Related Local Side Effects in the Treatment of Diabetes Mellitus: A Methodological Approach and Possible Solutions. Consensus Statement of Amd-Osdi Study Group on Injection Technique. In e-book Diabetes Compòications. 2016. www.smgebooks.com/diabetic-complica-tions/index.php. Accessed March 28, 2022.
Gentile S, Strollo F. Cost saving effects of a short-term edu-cational intervention entailing lower hypoglycaemic event rates in people with type 1 diabetes and lipo-hypertrophy. Diabetes Res Clin Pract. 2018; 143: 320-321. doi: 10.1016/j.diabres.2018.07.030
Gentile S, Guarino G, Della Corte T. The economic burden of insulin injection-induced lipohypertophy. Role of education: The ISTERP-3 Study. Adv Therap. 2022; 39: 2192-2207. doi: 10.1007/ s12325-022-02105-5
Gentile S, Guarino G, Della Corte T, et al. Role of structured education in reducing lypodistrophy and its metabolic complica-tions in insulin-treated people with type 2 diabetes: A randomized multicenter case-control study. Diabetes Ther. 2021; 12(5): 1379- 1398. doi: 10.1007/s13300-021-01006-0
Gentile S, Guarino G, Della Corte T, et al. The durability of an intensive, structured education-based rehabilitation protocol for best insulin injection practice: The ISTERP-2 study. Diabetes Ther. 2021; 12(9): 2557-2569. doi: 10.1007/s13300-021-01108-9
Valentini U, Bonfadini S, Turra V. L’educazione Terapeutica per la persona con diabete. In Educare alla Salute e all’Assistenza. 2021. https://www.aprirenetwork.it/2021/06/10/cap-24-ledu-Mini Review | Volume 8 | Number 1 | cazione-terapeutica-per-la-persona-con-diabete. Accessed March 28, 2022.
Miller LV, Goldstein J. More efficient care of diabetic patients in a county-hospital setting. N Engl J Med. 1972; 286(26): 1388- 1391. doi: 10.1056/NEJM197206292862605
Ceriello A, Monnier L, Owens D. Glycaemic variability in dia-betes: Clinical and therapeutic implications. Lancet Diabetes Endo-crinol. 2019; 7: 221-230. doi: 10.1016/S2213-8587(18)30136-0
Shen M, Shi Y, Zheng S, Fan H, Xu J, Yang T. A systematic survey of physicians’ insights into lipohypertrophy. Front Public Health. 2021; 9: 738179. doi: 10.3389/fpubh.2021.738179
Gentile S, Strollo F, Ceriello A. Lipodistrophy and associated risk factors in insulin-treated people with diabetes. Int J Endocrinol Metab. 2016; 14(2): e33997. doi: 10.5812/ijem.33997
Wu X, Zhao F, Zhang M, et al. Insulin injection knowledge, attitudes, and practices of nurses in China: A cross-sectional nationwide study. Diabetes Ther. 2021; 12(9): 2451-2469. doi: 10.1007/s13300-021-01122-x
Fujikura J, Fujimoto M, Yasue S, et al. Insulin-induced lipo-hypertrophy: report of a case with histopathology. Endocr J. 2005; 52(5): 623-628. doi: 10.1507/endocrj.52.623
Gentile S, Guarino G, Corte TD, et al. Insulin-induced skin lipohypertrophy in Type 2 diabetes: a multicenter regional sur-vey in Southern Italy. Diabetes Ther. 2020; 11(9): 2001-2017. doi: 10.1007/s13300-020-00876-0
Scaramuzza EA, Ferrari M, Gian Vincenzo Zuccotti GV. Elastargene 3C helps to improve glycated haemoglobin in chil-Submit your article to this journal | https://openventio.org/submit-manuscript/ Mini Review | Volume 8 | Number 1 | Gentile S, et al dren and adolescents with type 1 diabetes using insulin pump therapy. 2015. https://www.easd.org/virtualmeeting/home. html#!resources/elastargene-3c-helps-to-improve-glycated-hae-moglobin-in-children-and-adolescents-with-type-1-diabetes-us-ing-insulin-pump-therapy--2. Accessed March 28, 2022.
Di Bartolo P, Eckel RH, Strollo F, Gentile S. Hundred-year experience with insulin and lipohypertrophy: An unresolved is-sue. Diabetes Res Clin Pract. 2021; 178: 108924. doi: 10.1016/j.di-abres.2021.108924
American Diabetes Association. Introduction: Standards of medical care in diabetes—2022. Diabetes Care. 2022; 45(Suppl.
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