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1

Hansenne, Isabelle Sylvie, Chantal Renard i Vincent Geenen. "Igf2 expression is required for complete tolerance to insulin (128.19)". Journal of Immunology 178, nr 1_Supplement (1.04.2007): S213—S214. http://dx.doi.org/10.4049/jimmunol.178.supp.128.19.

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Abstract All members of insulin gene family are transcribed in human thymus according a hierarchy whereby IGF2 expression (thymic epithelial cells/TEC) exceeds IGF1 (macrophages), which exceeds INS (medullary TEC). Type 1 and type 2 IGF receptors are expressed by thymic T-cell populations. To further study the expression of IGF-2 in thymus, the dominance of this factor was compared to insulin, while ontogenesis of Igf2, insulin1 and insulin2 transcription was studied in Balb/c pancreas and thymus. In 4-wk old thymi, IGF-2 concentration is higher than insulin content. Ontogenesis of Igf2, insulin1 and insulin2 transcription from E13 to post-natal day 2 does not differ in Balb/c thymus and pancreas. In a second step, tolerance to IGF-2 and insulin was assessed by immunization of Igf2−/− mice. The profile of B-cell response in Igf2−/− mice immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 antibodies that was absent in Igf2+/+ mice. This T-dependent isotype switch indicates the presence of specific anti-IGF-2 CD4+ T cells. Cloning of these T cells failed because Igf2−/− CD4+ T cells exhibit a low rate of proliferation in presence of IGF-2. After immunization with insulin, Igf2−/− mice developed a significantly higher humoral response against insulin, indicating that Igf2 expression is necessary for complete tolerance to insulin.
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2

Shestakova, Marina Vladimirovna, i Irina Vladimirovna Glinkina. "Insulin glargine does not increase the risk of malignancy.Synopsis of the article ?Combined randomised controlled trial experience of malignancies in studies using insulin glargine?byHome P.D. & Lagarenne P. (Diabetologia 2009, vol. 52 (12): 2499-2506)". Diabetes mellitus 13, nr 1 (15.03.2010): 88–90. http://dx.doi.org/10.14341/2072-0351-6022.

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Results of 31 controlled randomized studies of insulin glargine given to patients with diabetes mellitus are reviewed to evaluate the frequency of malignantneoplasms. 52 tumours were diagnosed in 45 (0.8%) patients on insulin glargine therapy and 48 tumors in 46 (0.9%) patients using other insulins(mostly NPX insulin). The incidence of breast cancer was equal (0.1%) in both groups (4 and 6 cases respectively). These data indicate thatthe use of insuline glargine does not increase the risk of malignancy, e.g. breast cancer.
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3

Dąbrowski, Mariusz. "U kogo i dlaczego warto zastosować insulinę dwuanalogową aspart + degludec?" Medycyna Faktów 16, nr 2(59) (30.06.2023): 227–33. http://dx.doi.org/10.24292/01.mf.0223.15.

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Ostatnie lata przyniosły istotne zmiany paradygmatu terapii cukrzycy typu 2. Po ogłoszeniu wyników pierwszych i kolejnych badań bezpieczeństwa sercowo-naczyniowego leków przeciwcukrzycowych na pierwszą linię frontu wysunęły się leki nieinsulinowe, a szczególne miejsce zajęły inhibitory kotransportera sodowo-glukozowego typu 2 i agoniści receptora glukagonopodobnego peptydu-1 (te drugie są rekomendowane jako pierwsza terapia iniekcyjna w cukrzycy typu 2). Spowodowało to nieznaczny spadek liczby pacjentów leczonych insuliną. Niemniej należy pamiętać, że w populacji osób z cukrzycą typu 2 u wielu pacjentów wystąpi wcześniej lub później konieczność wdrożenia insulinoterapii. Zwykle jest ona inicjowana w postaci jednej iniekcji insuliny bazowej, przy czym w naszych warunkach zwykle jest to insulina NPH. Brak efektywności tej terapii wymaga dalszej intensyfikacji leczenia w postaci dołączania kolejnych iniekcji insuliny doposiłkowej. Jedną z takich opcji jest zastosowanie połączenia w jednym wstrzykiwaczu szybko działającego analogu – insuliny aspart (IAsp) oraz ultradługo działającego analogu – insuliny degludec (IDeg), z których każdy zachowuje swój profil farmakokinetyczny. Zaletą tej opcji jest mniejsza liczba iniekcji przy porównywalnej lub lepszej kontroli glikemii w porównaniu z innymi schematami terapii, a dodatkową korzyścią dla pacjenta jest mniejsza liczba hipoglikemii, szczególnie nocnych. Leczenie to umożliwia dalszą intensyfikację terapii poprzez dodanie drugiej iniekcji IDegAsp lub kolejnych iniekcji insuliny doposiłkowej. Insulina IDegAsp może być też użyta przy inicjowaniu insulinoterapii w warunkach znacznej hiperglikemii, przy zamianie terapii mieszankami insulin ludzkich bądź analogowych na jedną lub dwie iniekcje insuliny IDegAsp, a i to nie wyczerpuje pełnego spektrum jej możliwych zastosowań. Podsumowując, insulina IDegAsp jest wartościowym i bezpiecznym uzupełnieniem możliwości insulinoterapii u pacjentów z cukrzycą typu 2, ale też typu 1.
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4

Modi, K. D., Pradeep V. Gadge, Pradeep Jain, Sudhir Pawar, Ruchi D. Shah, Shahu A. Ingole i Rishi Jain. "Clinical challenges with excipients in insulin formulations and role of concentrated insulin". International Journal of Basic & Clinical Pharmacology 8, nr 4 (23.03.2019): 821. http://dx.doi.org/10.18203/2319-2003.ijbcp20191125.

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Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins.
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5

Ray, Sumit. "Insulin infusion protocol (Human insulin®/Insugen®)". Current Medicine Research and Practice 4, nr 4 (lipiec 2014): 186–87. http://dx.doi.org/10.1016/j.cmrp.2014.08.007.

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6

Kucera, Michelle L., i John P. Graham. "Insulin Lispro, a New Insulin Analog". Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 18, nr 3 (6.05.1998): 526–38. http://dx.doi.org/10.1002/j.1875-9114.1998.tb03116.x.

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Insulin lispro is a rapid‐acting insulin analog to regular insulin. Inversion of the proline‐lysine amino acid sequence at positions 28 and 29 on the B chain is responsible for its more rapid absorption, faster onset, and shorter duration of action compared with regular insulin. The fast onset of action allows for greater flexibility in dosing and mealtime scheduling. Insulin lispro provides equivalent or slightly improved glycemic control in patients with types I and II diabetes mellitus compared with regular insulin, without subsequent increases in hypoglycemic episodes. It also results in greater reduction in postprandial blood glucose excursion than regular insulin. Compared with other insulins, insulin lispro represents a more physiologic approach to exogenous insulin therapy.
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7

ZHANG, Zhou. "Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin". Science in China Series C 46, nr 5 (2003): 474. http://dx.doi.org/10.1360/01yc0295.

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8

Harned, Leighton Kahle, i Edward Chin. "PSUN278 Factitious hypoglycemia, diagnostic delay due to insulin assay failure to detect insulin analogues." Journal of the Endocrine Society 6, Supplement_1 (1.11.2022): A403. http://dx.doi.org/10.1210/jendso/bvac150.838.

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Abstract Factitious hypoglycemia may be difficult to diagnose clinically. Hypoglycemia due to insulin self-administration is established by the presence of a low c-peptide and elevated plasma insulin levels. Commercial insulin assays often fail to detect insulin analogs and can create confusion among providers investigating causes of hypoglycemia. A 20 year old female with no significant past medical history presented to an Emergency Room (ER) with hypoglycemia. She was treated with a single dose of octreotide 150 mcg, dexamethasone 10 mg PO and started on a D10W drip at 100ml/hr prior to transfer. Laboratory studies on transfer reported plasma glucose 52ng/dL (RR: 70-100), low C-peptide 0.02 (RR: 0.78-5.19), low insulin level <0.087 uIU/mL, normal IGF-I level 122 ng/mL (RR: 85-370). Normal IGF-II level 401 ng/mL (RR: 333-967), and low Pro-insulin level 1.8 pmol/L (RR: 3.6-22 pmol/L). Sulfonylurea Screen was negative. The patient and her mother both denied exogenous insulin use. The patient and her mother both work in healthcare. The patient's boyfriend has type 1 diabetes mellitus and the patient stated she keeps insulin in her purse for him. The patient was admitted for a 72 hour fast and remained normoglycemic. An aliquot of the admission ER insulin blood sample was sent to second laboratory utilizing an assay able to detect analog insulins. The patient's sample previously reporting an undetectable insulin level (<0.087 uIU/mL) now reported an insulin level 8 uIU/mL. Factitious hypoglycemia is a challenging clinical diagnosis. The term factitious implies an attempt to deceive and creates mistrust between the physician and patient. However, hypoglycemia may be the result of medication errors or administered by a second party with the intent to harm. Analog insulins (glargine, aspart, lispro, glulisine, etc) are genetically modified insulins developed to mimic the physiologic pattern of pancreatic beta cell insulin secretion. The amino acid modifications in analog insulins result in structural variations which alters the ability of highly specific commercial automated immunoassays to accurately quantitate these analog insulins. The variation in lab assay detection may cause confusion when interpreting the results. The DiaSorin Liaison XL platform in our hospital utilizes a chemiluminescence immunoassay which does not detect insulin analogs, but detects regular and NPH insulin as they are structurally identical to endogenous human insulin. The second laboratory uses the Siemens Advia Centaur platform, an immunoassay which reacts with insulin analogs "on a nearly equimolar basis with the analogs insulin aspart, insulin glargine, and insulin lispro. Insulin detemir exhibits approximately 50 percent cross-reactivity. Test reactivity with insulin glulisine is negligible (< 3 percent)". Many commercial insulin assays do not detect analog insulins and none qualitatively distinguish between different insulins. Failure to recognize this detection flaw may result in misdiagnosis, patient safety issues and costly unneeded additional studies Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
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9

Gargiulo, P., U. Di Mario, O. Zuccarini, F. Troili, C. Tiberti, U. Nicolini, A. Pachi, G. Gerlini i F. Fallucca. "Treatment of diabetic pregnant women with monocomponent insulins". Acta Endocrinologica 113, nr 3_Suppl (sierpień 1986): S60—S65. http://dx.doi.org/10.1530/acta.0.111s0060.

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Abstract. Very little immunological research has been undertaken in pregnant diabetic women in relation to insulin therapy. We investigated the relations between treatment with insulins of varied immunogenic character and the presence of immune factors such as insulin antibodies, immune complexes and insulin antiinsulin complexes as well as some maternal and neonatal complications of diabetic pregnancy. 128 insulin treated diabetic pregnant women and 121 of their newborns were included in the study. The incidence of insulin antibodies, immune complexes and insulin antiinsulin complexes was lower in patients treated with highly purified insulins than in those treated with conventional insulins. The insulin antibody levels were significantly related to the occurrence of maternal and neonatal morbibity. The presence of insulin antiinsulin complexes in the cord blood of infants of diabetic mothers was related to the presence of these complexes in their mothers. Our results seem to indicate that the use of highly purified insulin could favour the outcome of diabetic pregnancy.
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10

Mbanya, Jean Claude, Juergen Sandow, Wolfgang Landgraf i David R. Owens. "Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy". European Endocrinology 13, nr 01 (2017): 21. http://dx.doi.org/10.17925/ee.2017.13.01.21.

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Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications.
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11

Ahmed Aziz, Kamran Mahmood. "Role of New Insulin Analogs in the Management of Diabetes. A Clinical Review". Diabetes & Obesity International Journal 8, nr 1 (2023): 1–8. http://dx.doi.org/10.23880/doij-16000269.

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This paper has reviewed different insulin analogs currently available in the market and pharma industry, their safety, efficacy and their roles in the diabetes management, comparing with human regular and NPH insulin. Traditional insulins (human regular and NPH insulins) do not have constant or smoother pharmacokinetic and pharmacodynamic profiles and are usually associated with erratic blood glucose profiles with hypoglycemia or hyperglycemia when compared with analog insulins. Similarly they do not match physiologic insulin profiles with basal bolus format. According to the medical literature, current insulin analogs are more efficacious and also it has been documented in research trials that recent insulin analogs are better and safer as compared to human regular and NPH insulin in terms of hypoglycemia and HbA1c reductions. Hence this paper has reviewed these insulins analogs (longer acting basal and rapid acting insulin analogs) for their safety and efficacy in terms of hypoglycemia and HbA1c control, for the management of both type-1 and type-2 diabetics in hospitals and clinics.
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12

Hirsch, Irl B., Rattan Juneja, John M. Beals, Caryl J. Antalis i Eugene E. Wright. "The Evolution of Insulin and How it Informs Therapy and Treatment Choices". Endocrine Reviews 41, nr 5 (12.05.2020): 733–55. http://dx.doi.org/10.1210/endrev/bnaa015.

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Abstract Insulin has been available for the treatment of diabetes for almost a century, and the variety of insulin choices today represents many years of discovery and innovation. Insulin has gone from poorly defined extracts of animal pancreata to pure and precisely controlled formulations that can be prescribed and administered with high accuracy and predictability of action. Modifications of the insulin formulation and of the insulin molecule itself have made it possible to approximate the natural endogenous insulin response. Insulin and insulin formulations had to be designed to produce either a constant low basal level of insulin or the spikes of insulin released in response to meals. We discuss how the biochemical properties of endogenous insulin were exploited to either shorten or extend the time-action profiles of injectable insulins by varying the pharmacokinetics (time for appearance of insulin in the blood after injection) and pharmacodynamics (time-dependent changes in blood sugar after injection). This has resulted in rapid-acting, short-acting, intermediate-acting, and long-acting insulins, as well as mixtures and concentrated formulations. An understanding of how various insulins and formulations were designed to solve the challenges of insulin replacement will assist clinicians in meeting the needs of their individual patients.
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Peterson, Gregory E. "Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir". Current Medical Research and Opinion 22, nr 12 (1.12.2006): 2613–19. http://dx.doi.org/10.1185/030079906x154178.

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Dzhavakhishvili, T. S., T. I. Romantsova i O. V. Roik. "Influence of the dynamics of body weight on the risk factors of cardiovascular disease in patients with type 2 diabetes during the first year of insulin treatment". Obesity and metabolism 10, nr 1 (15.03.2013): 22–25. http://dx.doi.org/10.14341/2071-8713-5067.

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The aim of the present study was to investigate whether insulin treatment-induced weight gain had an adverse impact on cardiovascular risk factors in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy when insulin analogues or human insulins are used. A total of 157 patients with newly insulinized type 2 diabetes were included in the study. The patients were divided in two groups. First group consisted of subjects (mean age 57 [45; 73], duration of diabetes of 10 years [4; 16]) who had received long-acting basal (glargine, detemir), premixed (biphasic insulin aspart 30, Humalog Mix 25) or short-acting (aspart, lispro) insulin analogues. Patients from second group (mean age 59 [46; 75], duration of diabetes of 10 years [5; 15]) were treated with intermediate-acting basal (Protophane, Humulin NPH insulin), premixed (biphasic human insulin 30, Humulin M3) and regular (Actrapid, Humulin R) human insulins. Our study has shown that insulin-induced weight gain may not adversely affect cardiovascular risk factors, particularly, lipid profile, in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy. Use of insulin analogues for treatment of type 2 diabetes patients results in better glycaemic control, significant declines in blood lipid concentrations, less increase in waist circumference compared with human insulins during the first year after initiating insulin therapy.
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Danne, Thomas, i Jan Bolinder. "New Insulins and Insulin Therapy". Diabetes Technology & Therapeutics 15, S1 (luty 2013): S—40—S—47. http://dx.doi.org/10.1089/dia.2013.1505.

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Danne, Thomas, i Jan Bolinder. "New Insulins and Insulin Therapy". Diabetes Technology & Therapeutics 16, S1 (luty 2014): S—34—S—43. http://dx.doi.org/10.1089/dia.2014.1505.

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Bolinder, Jan, i Thomas Danne. "New Insulins and Insulin Therapy". Diabetes Technology & Therapeutics 17, S1 (luty 2015): S—39—S—46. http://dx.doi.org/10.1089/dia.2015.1505.

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Danne, T., i J. Bolinder. "New insulins and insulin therapy". International Journal of Clinical Practice 65 (luty 2011): 26–30. http://dx.doi.org/10.1111/j.1742-1241.2010.02576.x.

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Danne, Thomas, i Jan Bolinder. "New insulins and insulin therapy". International Journal of Clinical Practice 66 (luty 2012): 30–34. http://dx.doi.org/10.1111/j.1742-1241.2011.02851.x.

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Hale, Genevieve, Valerie Marcellus, Tina Benny, Cynthia Moreau, Elaina Rosario i Alexandra Perez. "Real-World Analysis of Long-Acting and NPH-Containing Insulins on Glycemic Control". Senior Care Pharmacist 39, nr 1 (1.01.2024): 42–49. http://dx.doi.org/10.4140/tcp.n.2024.42.

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Introduction Affordability of insulin products has become a concern in the past several years as the average price of various insulin products has increased. While awaiting legislation at the federal level that would address issues leading to high insulin costs, providers may have shifted prescribing practices to prescribe the lowest-priced insulin products to achieve patients’ treatment goals. Objective To compare the prevalence of hypoglycemic events between patients receiving lower-cost neutral protamine Hagedorn (NPH)-containing human insulins and higher-cost long-acting insulin analogs in Medicare Part D enrollees within a management services organization, as well as assessing glycemic control and changes in body mass index. Methods This was a multicenter, retrospective study conducted at three primary care clinics. The co-primary outcomes were percent difference of documented mild and severe hypoglycemic events between individuals receiving NPH-containing human insulin and long-acting insulin. Results A total of 72 patients met inclusion criteria and were receiving NPH-containing human insulins or the long-acting insulin analogs, 15 and 57 patients, respectively. Severe hypoglycemic events occurred in 3.5% vs 0% of the long-acting insulin analog and NPH-containing human insulin group, respectively (P = 0.999). Mild hypoglycemic episodes were experienced by 31.6% versus 33.3% of long-acting insulin analog and NPH, respectively (P = 0.539). For secondary outcomes, no difference was observed in glycemic control outcomes across insulin groups. Conclusion Among Medicare Part D patients with type 2 diabetes mellitus, the use of NPH-containing human insulins was not associated with an increased risk of mild or severe hypoglycemia-related episodes or reduced glycemic control compared with long-acting insulin. Study findings suggest that lower-cost, NPH-containing human insulins may be an alternative to higher-cost, long-acting insulin analogs.
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Jermendy, György. "Intensive conservative insulin treatment in patients with type 2 diabetes mellitus". Orvosi Hetilap 153, nr 38 (wrzesień 2012): 1487–93. http://dx.doi.org/10.1556/oh.2012.29451.

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In the last couple of years, the intensive conservative insulin treatment (basal-bolus regime) became more and more popular even in patients with type 2 diabetes. Using this insulin treatment, continuous patient education, co-operation between the medical team (diabetologist, dietician and diabetes-nurses) and the patient as well as the availability of modern insulins, pens and glucometers are of great importance. Clearly, the basal-bolus treatment with human insulin has advantages over the conservative (conventional) treatment with twice daily premix insulins. Moreover, the basal-bolus treatment with insulin-analogues proved to be superior in some aspects as compared to human insulins. The intensive insulin treatment (basal-bolus regime with insulin-analogues) approaches the optimal insulin substitution and, with its use the adequate correction of each element of the glucose triad (fasting blood glucose, postprandial blood glucose, HbA1c) should be considered feasible even in patients with type 2 diabetes. Orv. Hetil., 2012, 153, 1487–1493.
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Demidova, Tatiana Y., i Olga V. Balutina. "Special aspects of concentrated insulins: basic characteristics and research findings". Diabetes mellitus 22, nr 5 (17.01.2020): 481–90. http://dx.doi.org/10.14341/dm10334.

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The appearance of concentrated insulins in clinical practice determines the need to analyze product priorities in appropriate groups of patients with diabetes. The aim of this article is to summarize the literature on concentrated insulins (i.e. insulin lispro 200 units/mL, insulin degludec 200 units/mL, insulin glargine 300 units/mL) from randomized controlled trials, derive guidance on appropriate and safe use of these agents and demonstrate experience in real clinical practice. Severe hypoglycemia in all studies was generally low (though higher with prandial plus concentrated basal analogue therapy), and statistical improvements in other hypoglycemia categories were observed for concentrated basal insulins versus insulin glargine 100 units/mL. In all analyzed data hypoglycemic effect of insulin glargine 300 units/mL was equitable to insulin glargine 100 units/mL. Other important findings demonstrate more constant and prolonged insulin action with low within-subject/ between-day variability for insulin glargine 300 units/mL versus insulin glargine 100 units/mL, therefore, more physiological treatment might prevent from diabetic microvascular complications. The results of randomized trials are comparable with our clinical practice experience and indicate efficacious and safe glucose-lowering properties without risk of severe hypoglycemia.
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Mao, Xuhua, Hucheng Chen, Junmin Tang, Liangliang Wang i Tingting Shu. "Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction by inhibiting Pdx-1 expression". Endocrine Connections 6, nr 3 (kwiecień 2017): 121–28. http://dx.doi.org/10.1530/ec-16-0115.

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Objective Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. Design We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6. The downregulation of hepcidin decreased Pdx-1 expression, which reduced insulin synthesis. Methods MIN6 cells were exposed to high glucose concentrations (33.3 mmol/L). Glucose-stimulated insulin secretion (GSIS) and serum hepcidin levels were measured by ELISA. The mRNA levels of insulin1, insulin2, Pdx-1 and hepcidin were measured by real-time polymerase chain reaction. Western blot analysis was used to detect the changes in PDX-1 expression. Transient overexpression with hepcidin was used to reverse the downregulation of Pdx-1 and insulin synthesis induced by gluco-toxicity. Results Exposure of MIN6 cells to high glucose significantly decreased GSIS and inhibited insulin synthesis as well as Pdx-1 transcriptional activity and expression at both the mRNA and protein levels. High glucose also decreased hepcidin expression and secretion. Hepcidin overexpression in MIN6 cells partially reversed the gluco-toxicity-induced downregulation of Pdx-1 and insulin expression and improved GSIS. The restoration of insulin synthesis by transfection of a hepcidin overexpression plasmid confirmed the role of hepcidin in mediating the gluco-toxic inhibition of insulin synthesis. Conclusions Our observations suggest that hepcidin is associated with gluco-toxicity-reduced pancreatic β-cell insulin synthesis in type 2 diabetes by inhibiting Pdx-1 expression.
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Broussard, John D., i Mark E. Peterson. "Comparison of two ultralente insulin preparations with protamine zinc insulin in clinically normal cats". American Journal of Veterinary Research 55, nr 1 (1.01.1994): 127–31. http://dx.doi.org/10.2460/ajvr.1994.55.01.127.

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Summary The absorption kinetics and glycemic effects of 3 long-acting insulin preparations (protamine zinc beefpork insulin, ultralente beef-pork insulin, and ultralente human insulin) were evaluated in 9 healthy, adult, domestic shorthair cats (6 males, 3 females). A triple crossover study was performed, in which the serial serum concentrations of insulin and glucose were determined over a 24-hour period after SC administration of the 3 insulin preparations (dosage, 1.0 U/kg of body weight) at 3-week intervals. A control study was also performed in 4 of the cats by serially collecting samples for insulin and glucose determinations after administration of insulin diluent. After administration of protamine zinc insulin (pzi), mean (± sem) serum insulin concentration increased significantly (P < 0.05) above baseline, reached a peak value (484 ± 287 pmol/L) at 1 hour, and remained significantly (P < 0.05) higher than baseline at 24 hours. After administration of ultralente human insulin, the serum insulin curve was similar to that obtained after pzi administration, but mean serum insulin concentration took longer to peak (538 ± 177 pmol/L at 4 hours). After administration of ultralente beef-pork insulin, mean peak serum insulin concentration was lower (220 ± 54 pmol/L, not statistically significant) than that obtained after administration of pzi and ultralente human insulins; it then decreased to values statistically indistinguishable from baseline by 16 hours. The area under the serum insulin concentration curve for pzi (5,063 ±681 pmol • h/L) and ultralente human insulin (4,138 ± 439 pmol • h/L) was significantly (P < 0.05) larger than that for ultralente beef-pork insulin (2,378 ± 561 pmol • h/L). Serum glucose concentration decreased after administration of all 3 insulins, but the decrease was not different from that observed after diluent (control) administration. Results of this study indicate that differences may exist between absorption of pzi, ultralente human, and ultralente beef-pork insulins. Of the 2 ultralente insulin preparations, human insulin appears better absorbed than beef-pork insulin, but these findings need to be confirmed in cats with naturally acquired diabetes mellitus.
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25

Diaz, J. L., i T. J. Wilkin. "Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies." Clinical Chemistry 34, nr 2 (1.02.1988): 356–59. http://dx.doi.org/10.1093/clinchem/34.2.356.

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Abstract Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important.
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26

Kumar, Sinha Ritesh, i Chandra Satish. "Insulin resistance". Asian Pacific Journal of Health Sciences, Supplimentary 2014 (2014): 71–78. http://dx.doi.org/10.21276/apjhs.2014.1.1s.15.

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27

Petrukhin, Aleksey. "Pump Insulin Therapy and Continuous Glycemic Monitoring". Spravočnik vrača obŝej praktiki (Journal of Family Medicine), nr 6 (1.06.2020): 26–32. http://dx.doi.org/10.33920/med-10-2006-03.

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Diabetes mellitus is a chronic disease, which is based on insufficient insulin production, which ultimately leads to the development of hyperglycemia. As a result of the continuous increase in blood sugar levels, many organs and systems suffer, and diabetes is one of the common causes of disability. After the discovery of the true nature of the disease, the main method of treatment is the administration of insulin. The dose and frequency of administration of this drug are selected individually and can be adjusted during treatment. The insulins used at the present stage are represented by ultra-short, short-acting, mediumduration and slow-acting drugs. Ultrashort and short-acting insulins begin to work literally in a few minutes after administration, but the effect persists for a short time. This type of insulin is indicated for subcutaneous administration before meals or immediately after it. Medium and slow-acting insulins are meant to maintain insulin at a certain level for a long time, they are administered at the same time, usually twice a day. Short and ultrashort insulins should be injected into the subcutaneous tissue of the abdomen, while taking into account that the greater the thickness of the subcutaneous fat layer, the slower the absorption. Slow-acting insulins are recommended to be administered to the outer surface of the thigh or buttocks. Insulin is administered using insulin syringes or pen injectors. At present, the use of insulin pumps, which provide continuous supply of insulin using a special device, has become an alternative to the syringe administration of short-acting and ultra-short insulins. Often, such devices are equipped with glucose level sensors, which allows continuous monitoring of blood sugar levels.
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28

Dzhavakhishvili, T. Sh, T. I. Romantsova i O. V. Roik. "Dinamika massy tela u bol'nykh sakharnymdiabetom 2 tipa v techenie pervogo godainsulinoterapii". Obesity and metabolism 7, nr 4 (15.12.2010): 13–19. http://dx.doi.org/10.14341/2071-8713-5082.

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The aim of this study was to determine changes in weight and insulin requirements in insulin-treated type 2 diabetic patients with normal and elevated body mass index (BMI) during the first year after initiating the insulin therapy with insulin analogues or human insulins, respectively. Materials and methods: a total of 157 patients with insulin naive type 2 diabetes were included in the study. The patients were divided in two groups. First group consisted of subjects [mean age 57 (45 to 73), duration of diabetes of 10 years (4 to 16)] prescribed a long-acting basal (glargine, detemir), premixed (biphasic insulin Aspart 30, Humalog Mix 25) or short-acting (aspart, lispro) insulin analogues. Patients from second group [mean age 59 (46 to 75), duration of diabetes for 10 years (5 to 15)] were treated with intermediate- acting basal (Protophane, Humulin NPH), premixed (biphasic human insulin 30, Humulin M3) and regular (Actrapid, Humulin R) human insulins. Each of these two groups was divided into three subgroups depending on the baseline body mass index (BMI) of the patients: 18,5-24,9; 25-29 and ≥30. At the beginning of insulin therapy and 12 months later, we compared HbA1c, BMI, waist circumference and required insulin doses in each group. Results: our study results showed that under comparable metabolic control the risk for weight gain and increase in insulin requirement is similar in insulin-treated type 2 diabetic patients with normal and elevated BMI. Use of insulin analogues for treatment of type 2 diabetes patients with normal and elevated BMI results in better glycaemic control, less weight gain, smaller increase in insulin requirement and waist circumference compared to human insulins during the first year of insulin therapy.
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29

Bansal, Naresh, Narendra Kotwal, Anuj Singhal i Ashish Kumar. "Insulin: The Journey Continues". Journal of Marine Medical Society 26, nr 1 (1.09.2023): 3–8. http://dx.doi.org/10.4103/jmms.jmms_90_23.

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Abstract In the history of medicine, the discovery of insulin marked a turning point. At first, the only form of insulin that could be administered to humans was this secretion from animal pancreas. Since its conception, technologies for purifying and altering insulin have been developed, although they are still a long way from simulating pancreatic-cells’ natural production. The precise structure of the insulin molecule had been uncovered by the late 1950s, and with the development of molecular biology and recombinant DNA techniques, it is now feasible to manipulate genes to produce recombinant human insulins. This opened the door for the creation of short-acting analogs to mimic postprandial insulin secretion and long-acting analogs to mimic basal or background insulin secretion. The patients can more closely mimic pancreatic insulin secretion thanks to the characteristics of the new basal and bolus analogs than they could with the earlier insulins. However, there are still issues with the absence of portal delivery, night-time dip, morning surge, and responsiveness to ambient blood glucose. There are a number of noninvasive methods being researched for the delivery of insulin, including transdermal, buccal, oral, and pulmonary routes. The hunt for insulin that precisely mirrors the physiological profile and has improved stability, less variability, and perhaps selective action, is still ongoing.
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30

Sandow, Juergen, Wolfgang Landgraf, Reinhard Becker i Gerhard Seipke. "Equivalent Recombinant Human Insulin Preparations and their Place in Therapy". European Endocrinology 11, nr 1 (2015): 10. http://dx.doi.org/10.17925/ee.2015.11.01.10.

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Recombinant human insulin was one of the first products of biotechnology. It was developed in response to the need for a consistent and sufficient worldwide supply. Recombinant human insulin replaced the animal insulins and semisynthetic insulins obtained by modification of animal insulins. Bioequivalence studies were required for regulatory approval. Three reference products were independently established during these procedures: Humulin® (Eli Lilly and Co), Novolin® (NovoNordisk) and Insuman® (Sanofi). Numerous brand names have been used during the commercial development of recombinant human insulin formulations. In this review, three current brand names are used for consistent identification. Human insulin for Humulin and Insuman are produced by fermentation in bacteria (Escherichia coli) and for Novolin in yeast (Saccharomyces cerevisiae). The bioequivalence of recombinant human insulin products was investigated in euglycaemic clamp studies. An overview of such bioequivalence studies is provided here. This paper will consider the relevance of human insulin formulations today and their place in therapy.
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31

Rosenstock, Julio, Harpreet S. Bajaj, Ildiko Lingvay i Simon R. Heller. "Clinical perspectives on the frequency of hypoglycemia in treat-to-target randomized controlled trials comparing basal insulin analogs in type 2 diabetes: a narrative review". BMJ Open Diabetes Research & Care 12, nr 3 (maj 2024): e003930. http://dx.doi.org/10.1136/bmjdrc-2023-003930.

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The objective of this review was to comprehensively present and summarize trends in reported rates of hypoglycemia with one or two times per day basal insulin analogs in individuals with type 2 diabetes to help address and contextualize the emerging theoretical concern of increased hypoglycemic risk with once-weekly basal insulins.Hypoglycemia data were extracted from treat-to-target randomized clinical trials conducted during 2000–2022. Published articles were identified on PubMed or within the US Food and Drug Administration submission documents. Overall, 57 articles were identified: 44 assessed hypoglycemic outcomes in participants receiving basal-only therapy (33 in insulin-naive participants; 11 in insulin-experienced participants), 4 in a mixed population (insulin-naive and insulin-experienced participants) and 9 in participants receiving basal-bolus therapy. For the analysis, emphasis was placed on level 2 (blood glucose <3.0 mmol/L (<54 mg/dL)) and level 3 (or severe) hypoglycemia.Overall, event rates for level 2 or level 3 hypoglycemia across most studies ranged from 0.06 to 7.10 events/person-year of exposure (PYE) for participants receiving a basal-only insulin regimen; the rate for basal-bolus regimens ranged from 2.4 to 13.6 events/PYE. Rates were generally lower with second-generation basal insulins (insulin degludec or insulin glargine U300) than with neutral protamine Hagedorn insulin or first-generation basal insulins (insulin detemir or insulin glargine U100). Subgroup categorization by sulfonylurea usage, end-of-treatment insulin dose or glycated hemoglobin reduction did not show consistent trends on overall hypoglycemia rates. Hypoglycemia rates reported so far for once-weekly basal insulins are consistent with or lower than those reported for daily-administered basal insulin analogs.
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32

Xu, Juan, Shanshan Zhang, Guohui Zhang, Lihua Huang i Qinghua Yi. "Research Progress on the Efficacy and Safety of Different Basal Insulins in the Treatment of Type 2 Diabetes Mellitus". Journal of Clinical and Nursing Research 8, nr 6 (22.07.2024): 21–25. http://dx.doi.org/10.26689/jcnr.v8i6.7670.

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Objective: To evaluate the efficacy and safety of different basal insulins in the treatment of type 2 diabetes mellitus (T2DM). Methods: The current research progress on different basal insulins was evaluated, with efficacy indicators including fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c), and safety indicators focusing mainly on weight change and the incidence of hypoglycemia. Results: Several different basal insulins showed similar metabolic control effects in terms of fasting plasma glucose and glycated hemoglobin. However, the risk of hypoglycemia was lower with insulin glargine 300 (Glar-300), insulin degludec 100 (Deg-100), and insulin degludec 200 (Deg-200) compared to insulin glargine 100 (Glar-100). Additionally, Glar-300 had the least impact on weight. Conclusion: For the treatment of T2DM, different basal insulins have similar therapeutic effects, but there are differences in the incidence of hypoglycemic events and their impact on weight. Rational insulin selection and dosage adjustments should be made based on the different patient groups.
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33

Andrade, Pedro, Luísa Barros i Margarida Gonçalo. "Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics". Anais Brasileiros de Dermatologia 87, nr 6 (grudzień 2012): 917–19. http://dx.doi.org/10.1590/s0365-05962012000600018.

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Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgEmediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients.
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34

Rasmussen, Jack T., i Heather J. Ipema. "Formulary Considerations for Insulins Approved Through the 505(b)(2) “Follow-on” Pathway". Annals of Pharmacotherapy 53, nr 2 (20.08.2018): 204–10. http://dx.doi.org/10.1177/1060028018795834.

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Objective: To summarize formulary-relevant issues for follow-on insulins approved through the Food and Drug Administration (FDA) 505(b)(2) approval pathway (Basaglar and Admelog). Data Sources: A search of the MEDLINE database was performed for articles pertaining to clinical and formulary considerations for follow-on insulin products through July 2018. Study Selection and Data Extraction: All clinical trials used in the 505(b)(2) approval process for follow-on insulin glargine and insulin lispro products were included and summarized. Data Synthesis: Follow-on insulin glargine and insulin lispro products have been recently approved as the first lower-cost alternatives to innovator insulin products. The follow-on insulins were approved via the 505(b)(2) pathway, making them neither generics nor biosimilars. Current data do not suggest any clinically relevant differences between the follow-on insulins and their respective innovator products. Clinicians should be aware that follow-on insulins will be reclassified as biologic products in the year 2020. Relevance to Patient Care and Clinical Practice: This article provides information about currently available follow-on insulin products that were approved through the 505(b)(2) pathway, including product characteristics and efficacy and safety data. These products will likely be considered for both clinical use and formulary placement because of their potentially lower cost compared with innovator products. Conclusions: Follow-on insulin products approved through the 505(b)(2) pathway are supported by robust efficacy and safety data. As new follow-on insulins are approved and the regulatory change that will occur with these products in 2020 approaches, formulary decisions and clinical policies (eg, substitution) will continue to be revisited.
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35

Bajaj, M., T. L. Blundell, R. Horuk, J. E. Pitts, S. P. Wood, L. K. Gowan, C. Schwabe, A. Wollmer, J. Gliemann i S. Gammeltoft. "Coypu insulin. Primary structure, conformation and biological properties of a hystricomorph rodent insulin". Biochemical Journal 238, nr 2 (1.09.1986): 345–51. http://dx.doi.org/10.1042/bj2380345.

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Insulin from a hystricomorph rodent, coypu (Myocaster coypus), was isolated and purified to near homogeneity. Like the other insulins that have been characterized in this Suborder of Rodentia, coypu insulin also exhibits a very low (3%) biological potency, relative to pig insulin, on lipogenesis in isolated rat fat-cells. The receptor-binding affinity is significantly higher (5-8%) in rat fat-cells, in rat liver plasma membranes and in pig liver cells, indicating that the efficacy of coypu insulin on receptors is about 2-fold lower than that of pig insulin. The primary structures of the oxidized A- and B-chains were determined, and our sequence analysis confirms a previous report [Smith (1972) Diabetes 21, Suppl. 2, 457-460] that the C-terminus of the A-chain is extended by a single residue (i.e. aspartate-A22), in contrast with most other insulin sequences, which terminate at residue A21. In spite of a large number of amino acid substitutions (relative to mammalian insulins), computer-graphics model-building studies suggest a similar spatial arrangement for coypu insulin to that for pig insulin. The substitution of the zinc-co-ordinating site (B10-His----Gln) along with various substitutions on the intermolecular surfaces involved in the formation of higher aggregates are consistent with the observation that this insulin is predominantly ‘monomeric’ in nature. The c.d. spectrum of coypu insulin is relatively similar to those of casiragua insulin and of bovine insulin at low concentration.
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36

Thomas, J. W., V. J. Virta i L. J. Nell. "Heterogeneity and specificity of human anti-insulin antibodies determined by isoelectric focusing." Journal of Immunology 134, nr 2 (1.02.1985): 1048–52. http://dx.doi.org/10.4049/jimmunol.134.2.1048.

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Abstract Anti-insulin antibodies are present in the majority of insulin treated diabetics, and in some cases these antibodies have been found to be highly specific for limited epitopes on the molecule. To determine how the human response differs from that seen in inbred animals, we have examined the heterogeneity and specificity of human anti-insulin antibodies by isoelectric focusing (IEF). In addition, we have used human insulin to examine the extent of autoreactivity in the serum of subjects treated with animal insulins. The majority of diabetic sera exhibited complex IEF spectra that were composed of discrete bands and unresolved smears. Autoradiography using 125I-beef, pork, and human insulin revealed some affinity differences; however, the predominant antibodies were capable of binding all insulins, including human. These specificity studies were extended by comparing competitive inhibition with excess cold insulins, and sera with highly specific binding of the A chain loop of beef insulin were identified. The spectra by IEF of these highly specific sera were found to be variable. Our results indicate that the majority of insulin-treated diabetics develop a heterogeneous antibody response that is more complex than the response of inbred animals and includes reactivity with autologous insulin. Although infrequent, individuals having antibodies directed at limited regions of the molecule can be identified and will provide valuable tools for dissecting this complex response.
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37

&NA;. "Insulin analogues show promise as short-acting insulins in insulin-dependent diabetes". Inpharma Weekly &NA;, nr 798 (sierpień 1991): 17. http://dx.doi.org/10.2165/00128413-199107980-00045.

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38

Gotham, Dzintars, Melissa J. Barber i Andrew Hill. "Production costs and potential prices for biosimilars of human insulin and insulin analogues". BMJ Global Health 3, nr 5 (wrzesień 2018): e000850. http://dx.doi.org/10.1136/bmjgh-2018-000850.

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IntroductionHigh prices for insulin pose a barrier to treatment for people living with diabetes, with an estimated 50% of 100 million patients needing insulin lacking reliable access. As insulin analogues replace regular human insulin (RHI) globally, their relative prices will become increasingly important. Three originator companies control 96% of the global insulin market, and few biosimilar insulins are available. We estimated the price reductions that could be achieved if numerous biosimilar manufacturers entered the insulin market.MethodsData on the price of active pharmaceutical ingredient (API) exported from India were retrieved from an online customs database. Manufacturers of insulins were contacted for price quotes. Where market API prices could not be identified, prices were estimated based on comparison of similarity, in terms of manufacturing process, with APIs for which prices were available. Potential biosimilar prices were estimated by adding costs of excipients, formulation, transport, development and regulatory costs, and a profit margin.ResultsThe manufacturing processes for RHI and insulin analogues are similar. API prices were US$24 750/kg for RHI, US$68 757/kg for insulin glargine and an estimated US$100 000/kg for other analogues. Estimated biosimilar prices were US$48–71 per patient per year for RHI, US$49–72 for neutral protamine Hagedorn (NPH) insulin and US$78–133 for analogues (except detemir: US$283–365).ConclusionTreatment with biosimilar RHI and insulin NPH could cost ≤US$72 per year and with insulin analogues ≤US$133 per year. Estimated biosimilar prices were markedly lower than the current prices for insulin analogues. Widespread availability at estimated prices may allow substantial savings globally.
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39

Duan, C., T. Noso, S. Moriyama, H. Kawauchi i T. Hirano. "Eel insulin: isolation, characterization and stimulatory actions on [35S]sulphate and [3H]thymidine uptake in the branchial cartilage of the eel in vitro". Journal of Endocrinology 133, nr 2 (maj 1992): 221–30. http://dx.doi.org/10.1677/joe.0.1330221.

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ABSTRACT Our previous studies have shown that mammalian and salmon insulins stimulate sulphate uptake by cultured eel cartilage, suggesting the possible involvement of insulin in the regulation of cartilage matrix synthesis. In the present study, homologous eel insulin was isolated and characterized, and its effects on cartilage matrix synthesis and DNA synthesis were examined in vitro. Insulin was extracted from eel pancreas with acid–ethanol, and subsequently purified by isoelectric precipitation at pH 5·3, gel filtration on Sephadex G-50, and reversed-phase high-performance liquid chromatography. The amino acid composition and complete sequence (50 residues) of eel insulin revealed high homology to teleostean and mammalian insulins. The isolated eel insulin produced a more pronounced and longer lasting hypoglycaemic effect than bovine insulin in the eel. Homologous eel insulin, like bovine insulin-like growth factor (IGF-I) and insulin, stimulated sulphate uptake by cultured eel cartilage in a dose-dependent manner (16–1000 ng/ml). Combination experiments using maximal concentrations of bovine IGF-I (250 ng/ml) and increasing amounts of eel insulin (10–250 ng/ml) showed no additive effects of insulin on sulphate uptake, suggesting that insulin and IGF-I may share a common mechanism(s) of action. Eel insulin and bovine IGF-I also enhanced thymidine incorporation by eel cartilage in a dose-dependent manner (4–1000 ng/ml); eel insulin was equipotent with bovine IGF-I. These results suggest that insulin, like IGF-I, may exert direct growth-promoting actions in branchial cartilage of the eel. Journal of Endocrinology (1992) 133, 221–230
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40

Taylor, M. Joan, Krishan P. Chauhan i Tarsem S. Sahota. "Glucose lowering strategies with insulin". British Journal of Diabetes 19, nr 2 (17.12.2019): 124–30. http://dx.doi.org/10.15277/bjd.2019.228.

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People with type 1 diabetes must use insulin and a large fraction of those with type 2 condition also do so. Many therefore struggle with the unpredictable balancing of insulin dose with calorie intake and utility. A healthy pancreas makes meticulous adjustment on a continuous basis that present therapeutic insulin administration cannot match. However, much progress has been made to make it simpler to inject both background and fast-acting boost insulins with a view to better mimicking normal pancreatic output. The present fast insulins are reviewed with accent on the primary amino acid structures of the biosynthetic types that diffuse more quickly than regular insulin that associates in hexamers. This makes boost doses kinetically and clinically more effective, allowing people to inject better estimated boost and corrective doses. Formulation advances are discussed for their present and potential contributions. The newer slow-acting insulins are also described and compared, their advantage also being kinetic with a lower likelihood of inducing overnight hypoglycaemia when used optimally. Finally, the appreciation of the advantages of alternative routes of administration such as oral and peritoneal are included in this review because of the possibility of altering the hepatic to peripheral ratio, the reasons for which are more effective but less obesogenic insulin activity. The logistics of oral insulin are summarised in terms of the risks to the insulin structure, the facilitation of paracellular uptake at the apical surface and the paradoxically advantageous hepatic first pass. Other non-invasive routes are also included in the review.
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41

&NA;. "Insulin/insulin aspart/insulin glargine". Reactions Weekly &NA;, nr 1338 (luty 2011): 24. http://dx.doi.org/10.2165/00128415-201113380-00077.

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42

Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 23, S2 (1.06.2021): S—46—S—68. http://dx.doi.org/10.1089/dia.2021.2504.

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Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 18, S1 (luty 2016): S—43—S—55. http://dx.doi.org/10.1089/dia.2016.2505.

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Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 19, S1 (luty 2017): S—42—S—58. http://dx.doi.org/10.1089/dia.2017.2505.

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Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 20, S1 (luty 2018): S—55—S—70. http://dx.doi.org/10.1089/dia.2018.2505.

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46

Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 21, S1 (luty 2019): S—57—S—78. http://dx.doi.org/10.1089/dia.2019.2505.

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47

Danne, Thomas, Lutz Heinemann i Jan Bolinder. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 22, S1 (1.02.2020): S—32—S—46. http://dx.doi.org/10.1089/dia.2020.2503.

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48

Danne, Thomas, Lutz Heinemann i Thomas R. Pieber. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 25, S1 (1.02.2023): S—44—S—69. http://dx.doi.org/10.1089/dia.2023.2504.

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49

Danne, Thomas, Lutz Heinemann i Thomas R. Pieber. "New Insulins, Biosimilars, and Insulin Therapy". Diabetes Technology & Therapeutics 26, S1 (1.03.2024): S—45—S—67. http://dx.doi.org/10.1089/dia.2024.2504.

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50

Andrianova, E. A. "The use of ultra-short acting insulin preparations for insulin pumps". Problems of Endocrinology 58, nr 3 (15.06.2012): 46–50. http://dx.doi.org/10.14341/probl201258346-50.

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The data on the efficacy of using ultra-short acting insulin preparations in insulin pumps for children and adolescents presenting with diabetes mellitus. Insulin pump therapy in the patients of these age groups is finding an increasingly wider application as being more convenient for the users and leading to the improvement of glycemic control. One of the main advantages of modern insulin pump therapy is the possibility to maximally imitate the physiological profile of insulin secretion. The flexibility of both basal and bolus dosing regimens of insulin administration can be further increased by using ultra-short acting insulin preparations in insulin pumps. The choice of any of the three currently available analogs of ultra-short acting insulin guarantees their identical efficacy and safety in the children and adolescents with type 1 diabetes mellitus. They can be recommended as insulins of choice for the use in pump therapy
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