Articles de revues : « Analoghi insulina »

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Valenzano, M. « Insulin : 100 years but not over the hill ! A treatment with potential for renewal ». Journal of AMD 25, n^o 2 (juillet 2022) : 97. http://dx.doi.org/10.36171/jamd22.25.2.

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L’insulina è ancora un trattamento fondamentale per molti pazienti con diabete. A un secolo dalla sua scoperta, nuovi analoghi sono in procinto di essere disponibili così da potenziare ulteriormente la farmacocinetica e la farmacodinamica della molecola, sia in termini di effetto sostenuto (per l’insulina basale settimanale) che di velocità d’azione (per gli analoghi ultrarapidi). Inoltre, penne intelligenti e nuovi dispositivi agevoleranno la somministrazione di insulina, fornendo anche supporto digitale per il calcolo della dose, il monitoraggio e l’analisi delle iniezioni e, si spera, saranno utili per l’economia e l’ecosistema del pianeta. Infine, la ricerca futura è orientata allo sviluppo dell’insulina orale e dell’insulina intelligente e glucosensibile. La storia dell’insulina è tuttora in fieri e riserverà ancora molte novità. PAROLE CHIAVE insulina; insulina basale settimanale; insulina ultrarapida; penna intelligente; insulina intelligente.

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Toni, Roberto. « Tipi di insulina e suoi analoghi a 100 anni dalla scoperta ». L'Endocrinologo 22, n^o 1 (février 2021) : 63–67. http://dx.doi.org/10.1007/s40619-021-00832-5.

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Veltroni, Alessio, Elisa Cosaro et Maria Vittoria Davì. « Caratteristiche clinico-patologiche, gestione clinica e prognosi dell’insulinoma maligno : studio multicentrico italiano ». L'Endocrinologo 22, n^o 2 (17 mars 2021) : 139–43. http://dx.doi.org/10.1007/s40619-021-00843-2.

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SommarioL’insulinoma maligno è un tumore neuroendocrino pancreatico estremamente raro ed è associato a una severa sindrome ipoglicemica che impatta negativamente sulla qualità di vita e sulla sopravvivenza dei pazienti affetti. La gestione terapeutica dell’insulinoma maligno è complessa sia per il controllo delle crisi ipoglicemiche, sia per il controllo della crescita tumorale. La sindrome ipoglicemica rappresenta una sfida terapeutica per l’endocrinologo in quanto spesso non è responsiva alla terapia medica sintomatica, in particolare al diazossido utilizzato in monoterapia o associato agli analoghi della somatostatina. Everolimus ha un ruolo nel trattamento delle crisi ipoglicemiche refrattarie da insulinoma maligno sia per l’azione di inibizione del rilascio di insulina che di insulino-resistenza. La chirurgia con approccio curativo dell’insulinoma maligno è raramente perseguibile a causa della diffusione metastatica, mentre la chirurgia a scopo di debulking può essere presa in considerazione in casi selezionati sia per il controllo sintomatico sia perché può aumentare l’efficacia delle terapie sistemiche o locoregionali. La terapia radiometabolica con analoghi caldi della somatostatina rappresenta un’opzione terapeutica nei pazienti con tumori a elevata espressione dei recettori della somatostatina sia per il controllo della sintomatologia che della crescita tumorale, sebbene l’esperienza negli insulinomi maligni sia piuttosto scarsa. Data la rarità della malattia, sono disponibili in letteratura solo descrizioni di singoli casi o studi condotti su casistiche limitate; pertanto, è difficile stabilire la sequenza terapeutica più efficace in questi casi. Recentemente è stato condotto uno studio multicentrico italiano, in 13 centri di riferimento, focalizzato sulle caratteristiche clinico-patologiche, sulle modalità di trattamento e sui fattori prognostici che condizionano decorso ed esito dell’insulinoma maligno allo scopo di individuare una strategia terapeutica mirata basata su criteri razionali ed evidenze cliniche. In questa rassegna verranno descritti i principali risultati dello studio che comprende una casistica tra le più ampie finora pubblicate.

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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder et Rashem Mothilal. « A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part two : Insulin degludec vs. insulin glargine U300 ». South African Family Practice 60, n^o 4 (28 août 2018) : 7–12. http://dx.doi.org/10.4102/safp.v60i4.4903.

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Glucose clamp studies form an integral part of the early development of insulin therapies. Data generated in these studies are used to establish pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the agents, but methodological differences confound comparison of results from different glucose clamp studies. The first part of this series on glucose clamp studies discussed practical tips for the interpretation of glucose clamp studies. The second part of the series compares the PK/PD profiles of longer-acting basal analogue insulins, insulin degludec (IDeg) and insulin glargine U300 (Gla-300). The patient populations for glucose clamp studies with these analogue insulins differ, and therefore direct comparison of the data is not always possible. The maximum duration of action of IDeg is reported as 42 h and that of Gla-300 as 36 h, translating to 24 h coverage. The plasma insulin concentration of IDeg is 56 times that of Gla-300. Results from phase III clinical trials for these analogue insulins confirm the predictability and low within-subject variability observed in glucose clamp studies. Insight into the PK/PD profiles of longer-acting basal analogue insulins allows the treating physician to utilise these characteristics to optimise the treatment of their patients with diabetes.

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Veikko, Dr, et A. Koivisto. « Analogi insulina ». Diabetes mellitus 2, n^o 4 (15 décembre 1999) : 29–34. http://dx.doi.org/10.14341/2072-0351-6130.

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Zac-Varghese, Sagen, Bev Summerhayes et Peter Winocour. « Managing type 1 diabetes in frailty ». BMJ Case Reports 15, n^o 12 (décembre 2022) : e253779. http://dx.doi.org/10.1136/bcr-2022-253779.

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Managing type 1 diabetes in frail elderly people can be logistically challenging, particularly for those living alone. District nurse visits are unpredictable and coincide poorly with meal time insulin regimes. Elderly people, particularly those with dementia, have variable oral intake and activity. For some, poor glycaemic control leads to frequent and prolonged inpatient admissions. The use of technology, such as flash glucose monitoring, and the use of analogue insulins can be helpful in this setting. Increased monitoring enables more accurate titration of insulin doses and the information can be accessed by healthcare professionals and carers remotely. Longer lasting analogue insulins allow for a greater margin of error in the timing of insulin administration.

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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder et Rashem Mothilal. « A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part one : The principles of glucose clamp studies ». South African Family Practice 60, n^o 3 (12 juillet 2018) : 8–12. http://dx.doi.org/10.4102/safp.v60i3.4874.

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Glucose clamp studies are used to determine pharmacokinetics (PK) and pharmacodynamics (PD) of analogue insulins. With the development of longer-acting basal analogue insulins, including glargine 300 (Gla-300) and insulin degludec (IDeg), results from numerous glucose clamp studies are readily available. However, interpreting PK/PD profiles in a scientifically sound manner can be a challenging feat. This is the first in a series of publications that will suggest practical tips for interpreting and comparing results from glucose clamp studies. Variations in the glucose clamp methodology, duration of clamp studies and glucose clamp targets influence the study design and results significantly. Selection of study populations, including healthy patients or patients with Type 1 or 2 diabetes mellitus, has important implications. The dose of study insulin should reflect that of the general treatment population, and ideally steady-state conditions should be used. During the study the plasma insulin concentration and glucose infusion rate describe the pharmacokinetics and pharmacodynamics of the study insulin. With these practical tips in mind, results of glucose clamp studies can be interpreted in a scientifically correct manner. The next article in this series will discuss the interpretation of PK/PD profiles using two newly developed longer-acting basal analogue insulins: Gla-300 and IDeg.

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Mbanya, Jean Claude, Juergen Sandow, Wolfgang Landgraf et David R. Owens. « Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy ». European Endocrinology 13, n^o 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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Noor Wafaa Hashim, Kadhim Ali Kadhim et Abbas Mahdi Rahmah. « Effect of human insulin and insulin analogue on some inflammatory markers and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents ». Al Mustansiriyah Journal of Pharmaceutical Sciences 21, n^o 2 (19 avril 2022) : 9–14. http://dx.doi.org/10.32947/ajps.v21i2.804.

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Background: Both human insulin and insulin analogue used in the treatment of type 1 diabetes mellitus. The modification in amino acids sequences of human insulin lead to produce analogue form which have a pharmacokinetic and pharmacodynamics effect near to normal human endogenous insulin release. Aim of study: This study designed to compare between the effect of each type of insulin on high sensitive C-reactive protein and interleukin-6 and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents. Study design: The study was enrolled on fifty-one Iraqi type 1 diabetic children and adolecence age range (6-18) year. The patients allocated into two groups, Group (1) includes 20 patients assigned to receive conventional human insulin (regular and NPH), and Group (2) includes 20 patients assigned to receive insulin analogue (insulin aspart and glargine) for three months. The inflammatory and antioxidant markers measured at baseline and after three months of intervention. Results: After three months of treatment, both insulin groups did not affect high sensetive C_reactive protein (hs-CRP) significantly from baseline to 3 months. Only insulin analogue reduced Interleukin-6 (IL-6) significantly, while human insulin reduced level of IL-6 but it was not statistically significant. Both therapies reduced total antioxidant capacity (TAOC) significantly; however, insulin analogue had higher reduction percentage (15.1% vs. 5.7%) compared to the conventional insulin. Conclusion: Only insulin analogue reduced IL-6 significantly. Both types of insulins did not effect on hs-CRP. Both therapies reduce TAOC significantly.

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AUTHIER, François, Gianni M. Di GUGLIELMO, Gillian M. DANIELSEN et John J. M. BERGERON. « Uptake and metabolic fate of [HisA8,HisB4,GluB10,HisB27]insulin in rat liver in vivo ». Biochemical Journal 332, n^o 2 (1 juin 1998) : 421–30. http://dx.doi.org/10.1042/bj3320421.

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Receptor-mediated endocytosis and subsequent endosomal proteolysis of [125I]TyrA14-[HisA8,HisB4,GluB10,HisB27]insulin ([125I]TyrA14-H2 analogue), an insulin analogue exhibiting a high affinity for the insulin receptor, has been studied in liver parenchymal cells by quantitative subcellular fractionation and compared with that of wild-type [125I]TyrA14-insulin. Whereas the kinetics of uptake of the H2 analogue by liver was not different from that of insulin, the H2 analogue radioactivity after the 2 min peak declined significantly more slowly. A significant retention of the H2 analogue compared with insulin in both plasma membrane and endosomal fractions was observed and corresponded to decreased processing and dissociation of the H2 analogue. Cell-free endosomes preloaded in vivo with radiolabelled ligands and incubated in vitro processed insulin and extraluminally released insulin intermediates at a 2–3-fold higher rate than the H2 analogue. In vitro proteolysis of both non-radiolabelled and monoiodinated molecules by endosomal lysates showed a decreased response to the endosomal proteolytic machinery for the H2 analogue. However, in cross-linking and competition studies the H2 analogue exhibited an affinity for insulin-degrading enzyme identical with that of wild-type insulin. Brij-35-permeabilized endosomes revealed a 2-fold higher rate of dissociation of insulin from internalized receptors compared with the H2 analogue. After the administration of a saturating dose of both ligands, a rapid and reversible ligand-induced translocation of insulin receptor was observed, but without receptor loss. The H2 analogue induced a higher receptor concentration and tyrosine autophosphorylation of the receptor β subunit in endosomes. Moreover, a prolonged temporal interaction of the in vivo injected H2 analogue with receptor was observed by direct binding assays performed on freshly prepared subcellular fractions. These results indicate that endosomal proteolysis for the H2 analogue is slowed as a result of an increased residence time of the analogue on the insulin receptor and a low affinity of endosomal acidic insulinase for the dissociated H2 molecule.

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Demidova, Tatiana Y., et Olga V. Balutina. « Special aspects of concentrated insulins : basic characteristics and research findings ». Diabetes mellitus 22, n^o 5 (17 janvier 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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Ewen, Margaret, Huibert-Jan Joosse, David Beran et Richard Laing. « Insulin prices, availability and affordability in 13 low-income and middle-income countries ». BMJ Global Health 4, n^o 3 (juin 2019) : e001410. http://dx.doi.org/10.1136/bmjgh-2019-001410.

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IntroductionGlobally, one in two people needing insulin lack access. High prices and poor availability are thought to be key contributors to poor insulin access. However, few studies have assessed the availability, price and affordability of different insulin types in low-income and middle-income countries in a systematic way.MethodsIn 2016, 15 insulin price and availability surveys were undertaken (using an adaptation of the WHO/Health Action International medicine price and availability measurement methodology) in Brazil, China (Hubei and Shaanxi Provinces), Ethiopia, Ghana, India (Haryana and Madhya Pradesh States), Indonesia, Jordan, Kenya, Kyrgyzstan, Mali, Pakistan, Russia (Kazan Province) and Uganda. Data were collected in three sectors (public, private pharmacies and private hospitals/clinics) in three regions per survey. Insulin prices were standardised to 10 mL 100 IU/mL in US dollars ($). Data were also collected for four comparator medicines.ResultsMean availability was higher for human (55%–80%) versus analogue insulins (55%–63%), but only short-acting human insulin reached 80% availability (public sector). Median government procurement prices were $5 (human insulins) and $33 (long-acting analogues). In all three sectors, median patient prices were $9 for human insulins. Median patient prices for analogues varied between the public sector ($34) and the two private sectors ($44). Vials were cheaper than pens and cartridges. Biosimilars, when available, were mostly cheaper than originators. A low-income person had to work 4 and 7 days to buy 10 mL human and analogue insulin, respectively. For isophane human insulin, only three countries meet the WHO target of 80% availability of affordable essential medicines for non-communicable diseases in any sector.ConclusionImproving insulin availability and affordability needs to be addressed through national and global actions, including prioritising the supply of more affordable human insulin, increasing competition through the use of lower priced quality-assured biosimilars, negotiating lower prices from manufacturers and improving distribution systems.

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Freeman, Jeffrey S. « Are Analogue Insulins Superior to Human Insulin in Clinical Practice ? » Current Diabetes Reports 10, n^o 3 (26 mars 2010) : 176–83. http://dx.doi.org/10.1007/s11892-010-0104-8.

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Ferencz, Viktória, Beatrix Domján, László Gerő, Tímea Tänczer et Gy Ádám Tabák. « A normoglykaemia elérésének korlátai inzulinkezelt 2-es típusú cukorbetegekben ». Orvosi Hetilap 156, n^o 36 (septembre 2015) : 1443–50. http://dx.doi.org/10.1556/650.2015.30239.

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Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia. Orv. Hetil., 2015, 156(36), 1443–1450.

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Flekač, Milan. « Faster Insulin Aspart - a new prandial insulin analogue ». Vnitřní lékařství 63, n^o 10 (1 octobre 2017) : 697–702. http://dx.doi.org/10.36290/vnl.2017.138.

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Mathiesen, Elisabeth R. « Insulin Aspart in Diabetic Pregnancy : State of the Art ». Women's Health 4, n^o 2 (mars 2008) : 119–24. http://dx.doi.org/10.2217/17455057.4.2.119.

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Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe.

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J, Fövényi, Pánczél P et Thaisz E. « Healthy Pregnancy and Birth during Unusually Long-Lasting Remission of Type-1 Diabetes : Case Report ». Asploro Journal of Biomedical and Clinical Case Reports 3, n^o 1 (2 janvier 2020) : 1–5. http://dx.doi.org/10.36502/2019/asjbccr.6175.

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The 26-year-old woman was diagnosed with type 1 diabetes in 2014. The diagnosis was confirmed while there was a slight increase in blood glucose and HbA1c levels using oral glucose tolerance test, determination of insulin levels and GADA testing. This was followed by a 2-year period with complete remissions and partial remissions of 2-8 U daily basal insulin glargine. Thereafter, the patient became pregnant. The minimal basal insulin used to date has been switched to human rapid-acting and NPH insulins five times daily, which had to be increased to 11 times the initial dose in the third trimester of pregnancy. After a successful spontaneous birth of a healthy baby girl, our patient wished to return to one-tenth of the maximum insulin dose that was used during pregnancy, to once daily insulin glargine. After three months, her blood glucose levels began to rise, with oral glucose challenge test showing a marked increase in blood glucose and a drastic reduction in C-peptide levels. This was when we switched to multiple daily insulin administration using glargine basal- and glulisine analogue insulins. Later, glargine was switched to insulin degludec, and with a 30-33 U total daily insulin dose and CGM for the past two years, the patient was in a satisfactory metabolic state.

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Galstyan, Gagik Radikovich. « National advisory board on diabetes mellitus : unsolved issues and new opportunities for diabetes treatment ». Diabetes mellitus 17, n^o 3 (13 août 2014) : 129–33. http://dx.doi.org/10.14341/dm20143129-133.

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In June 2014, the national experts on diabetes mellitus discussed the opportunities to improve the efficacy and outcomes of diabetes treatment using the strategy of patient-oriented care in diabetes. Insulin degludec (Tresiba?) is a new basal ultra-long-acting insulin analogue with a flat, stable glucose-lowering profile, ultra-long duration of action (>=42 h) and less within-patient day-to-day variability in glucose-lowering effect compared with currently available basal insulins. In the clinical trial programme, insulin degludec showed a similar glycaemic control compared with insulin glargine using the same insulin dose, but with a lower risk of hypoglycaemia and a greater flexibility in the time of dosing on a daily basis, when needed. Thus, the use of insulin degludec in routine clinical practice provides an effective and improved treatment for type 1 and 2 diabetes. The simple algorithm titration of insulin degludec offers the opportunity to personalise treatment regimens according to the needs of each patient.

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Klimontov, Vadim Valer'evich, et Natalya Evgen'evna Myakina. « Insulin glargine : pharmacokinetic and pharmacodynamic basis of clinical effect ». Diabetes mellitus 17, n^o 4 (17 octobre 2014) : 99–107. http://dx.doi.org/10.14341/dm2014499-107.

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Glargine became the first long-acting insulin analogue. Glargine was designed to meet basal insulin requirements throughout the day with a single injection. Pharmacokinetics of insulin glargine is characterized by biotransformation into metabolites M1 and M2 that transforms the B chain of glargine so it is similar to the B chain of human insulin. Plasma concentrations of active M1 and M2 metabolites have no pronounced peaks during the day, resulting in lower glucose variability and hypoglycaemia risk when compared with NPH insulin. The metabolic activities of M1 and M2 metabolites are similar to the effect of glargine, whereas the mitogenic effects of these metabolites do not exceed the effect of human insulin. Insulin glargine shows a higher affinity for the insulin-like growth factor-1 (IGF-1) receptor when compared with human insulin. Glargine has no proliferative effect in vivo owing to its rapid conversion into metabolites. Pharmacokinetic and pharmacodynamic variability of glargine is comparable to other insulins. These characteristics are important for the clinical efficacy and safety of glargine.

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Khermansen, K., P. Fonten, K. K. Kukolyya, Valentina Alexandrovna Peterkova, G. Leyt et M. A. Gall. « Analogi insulina (insulin detemir i insulin aspart) v sravnenii s traditsionnymi chelovecheskimi insulinami (NPKh-insulinom i chelovecheskim insulinom korotkogo deystviya) v bazal'no-bolyusnoy terapii bol'nykh sakharnym diabetom 1 tipa ». Diabetes mellitus 9, n^o 1 (15 mars 2006) : 18–26. http://dx.doi.org/10.14341/2072-0351-5376.

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Koivisto, Veikko A. « The human insulin analogue insulin lispro ». Annals of Medicine 30, n^o 3 (janvier 1998) : 260–66. http://dx.doi.org/10.3109/07853899809005853.

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Kolbin, A. S. « Farmakoekonomicheskie aspekty primeneniya analogov insulina ». Diabetes mellitus 11, n^o 3 (15 septembre 2008) : 59–62. http://dx.doi.org/10.14341/2072-0351-5363.

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Mori, Yusaku, Eunhyoung Ko, Rudolf Furrer, Linda C. Qu, Stuart C. Wiber, I. George Fantus, Mario Thevis, Alan Medline et Adria Giacca. « Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats ». Endocrine Connections 7, n^o 5 (mai 2018) : 739–48. http://dx.doi.org/10.1530/ec-17-0358.

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It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague–Dawley rats fed a high-fat diet were given the carcinogen N-methyl-N-nitrosourea and randomly assigned to vehicle (control), NPH (unmodified human insulin), glargine or detemir (n = 30 per treatment). Insulins were given subcutaneously (15 U/kg/day) 5 days a week. Mammary tumours were counted twice weekly, and after 6 weeks of treatment, extracted for analysis. None of the insulin-treated groups had increased mammary tumour incidence at any time compared with control. At 6 weeks, tumour multiplicity was increased with NPH or glargine (P < 0.05) and tended to be increased with detemir (P = 0.2); however, there was no difference among insulins (number of tumours per rat: control = 0.8 ± 0.1, NPH = 1.8 ± 0.3, glargine = 1.5 ± 0.4, detemir = 1.4 ± 0.4; number of tumours per tumour-bearing rat: control = 1.3 ± 0.1, NPH = 2.2 ± 0.4, glargine = 2.7 ± 0.5, detemir = 2.3 ± 0.5). IGF-1R expression in tumours was lower than that in Michigan Cancer Foundation-7 (MCF-7) cells, a cell line that shows greater proliferation with glargine than unmodified insulin. In rats, glargine was rapidly metabolised to M1 that does not have greater affinity for IGF-1R. In conclusion, in this model of oestrogen-dependent breast cancer in insulin-resistant rats, insulin and insulin analogues increased tumour multiplicity with no difference between insulin types.

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Spiliopoulou, Maria, Alexandros Valmas, Dimitris-Panagiotis Triandafillidis, Stavroula Fili, Magdalini Christopoulou, Aikaterini J. Filopoulou, Anastasia Piskopou et al. « High-throughput macromolecular polymorph screening via an NMR and X-ray powder diffraction synergistic approach : the case of human insulin co-crystallized with resorcinol derivatives ». Journal of Applied Crystallography 54, n^o 3 (31 mai 2021) : 963–75. http://dx.doi.org/10.1107/s160057672100426x.

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Regular injections of insulin provide life-saving benefits to millions of diabetics. Apart from native insulin and insulin analogue formulations, microcrystalline insulin suspensions are also commercially available. The onset of action of the currently available basal insulins relies on the slow dissociation of insulin hexamers in the subcutaneous space due to the strong binding of small organic ligands. With the aim of identifying insulin–ligand complexes with enhanced pharmacokinetic and pharmacodynamic profiles, the binding affinity of two resorcinol-based molecules (4-chlororesorcinol and 4-bromoresorcinol) and the structural characteristics of insulin upon co-crystallization with them were investigated in the present study. `In solution' measurements were performed via saturation transfer difference (STD) NMR. Co-crystallization upon pH variation resulted in the production of polycrystalline precipitates, whose structural characteristics (i.e. unit-cell symmetry and dimension) were assessed. In both cases, different polymorphs (four and three, respectively) of monoclinic symmetry (P21 and C2 space groups) were identified via X-ray powder diffraction. The results demonstrate the efficiency of a new approach that combines spectroscopy and diffraction techniques and provides an innovative alternative for high-throughput examination of insulin and other therapeutic proteins.

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Jermendy, György, et Gábor Kovács. « A glargin és glulizin inzulinnal folytatott bázis-bolus kezelési rendszer egyéves eredményessége 2-es típusú cukorbetegségben. Elemzés a gyógyszerár-támogatás tükrében ». Orvosi Hetilap 159, n^o 50 (décembre 2018) : 2122–28. http://dx.doi.org/10.1556/650.2018.31214.

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Abstract: Introduction: Being entitled for no patient co-payment, the Hungarian reimbursement condition of analogue insulins as part of basal-bolus treatment in type 2 diabetes mellitus (T2DM) requires that two HbA1c levels should achieve <8.0% target value within 12 months (measured two months apart) after switching from treatment with human insulins. Achieving this target, the treatment should be considered effective from drug reimbursement perspective. Aim: The aims of the study were to investigate the effectiveness of insulin glargine + insulin glulisine basal-bolus regimen from the payer’s perspective and to investigate the ability to maintain the achieved glycaemic control in previously uncontrolled T2DM patients (HbA1c >9.0%). Method: This one-year, non-interventional study included patients with T2DM inadequately controlled (HbA1c >9.0%) on previous human basal-bolus treatment. The main outcomes were the proportion of patients who achieved the adequate glycaemic control (defined by the reimbursement rules) and the proportion of patients who achieved reimbursement rules defined HbA1c <8.0% target value by the 6 months after switch and could maintain this glycaemic control for upcoming further 6 months. As safety outcome, the hypoglycaemic events were recorded. Results: Out of the 557 patients enrolled, 287 had available data to be included in the efficacy analysis. Out of the 287 efficacy analysis patients, 169 (58.9%) achieved the reimbursement rules defined glycaemic control. At 6 months, 167 patients had HbA1c value <8.0% and 152 (91.0%) remained in this target range until the end of the 12-month observational period. Overall, 1221 non-severe and 6 severe hypoglycaemic events were reported. Conclusions: More than half of the patients with T2DM who were newly switched to insulin glargine + glulisine basal-bolus treatment could achieve the reimbursement rule criteria requiring for prescription of the analogue insulins with no co-payment beyond 1 year of treatment in Hungary. However, the results revealed that glycaemic control assessment with HbA1c measurements had not met the reimbursement requirements in a significant part of patients. Orv Hetil. 2018; 159(50): 2122–2128.

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Dayal, Devi, et Latika Rohilla. « Real-world experience of using basal insulin analogues in children with type 1 diabetes : is twice-daily dosing of insulin detemir justified ? » Pediatric Endocrinology Diabetes and Metabolism 25, n^o 2 (2019) : 103–5. http://dx.doi.org/10.5114/pedm.2019.85822.

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Hudson, E. K., D. Wang, L. L. Bieber, L. M. Buja et J. B. McMillin. « Increased carnitine palmitoyltransferase in cardiac myocytes is mediated by insulin growth factor I ». American Journal of Physiology-Heart and Circulatory Physiology 271, n^o 2 (1 août 1996) : H422—H427. http://dx.doi.org/10.1152/ajpheart.1996.271.2.h422.

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The mitochondrial carnitine palmitoyltransferase (CPT) system is composed of two proteins, CPT-I and -II, which, together with carnitine acylcarnitine translocase, are involved in the transport of fatty acids into the mitochondrial matrix for beta-oxidation. In the liver, CPT-I and its inhibition by malonyl-CoA are sensitive to hormonal (10(-9) M) levels of insulin; however, a similar effect of insulin on heart CPT is controversial. In cultured neonatal rat cardiac myocytes, tissue culture concentrations (1.7 microM) of insulin increase CPT and cytochrome oxidase activities as well as mitochondrial protein synthesis, suggesting that a growth mechanism may be involved. Because insulin at high concentrations may interact with the insulin-like growth factor (IGF-I) receptor, the consequences of insulin's action on heart cells in culture may be mediated through the IGF pathway. Consistent with an IGF-mediated pathway for the effect of insulin, incorporation of radioactivity into immunoprecipitated CPT-II from insulin-treated cardiac myocytes is dramatically increased over control cells. The amount of immunoreactive CPT-I is also increased in insulin-treated cells. Moreover, an IGF-I analogue that inhibits the autophosphorylation of the IGF-I receptor blunts the insulin-mediated increase in CPT-I and -II activities by > 70%. At low physiologically relevant concentrations (10 ng/ml), IGF-I significantly increases the activities of both CPT-I and -II, and the IGF-I analogue eliminates the IGF-I response. This is the first study to suggest involvement of the IGF-I pathway in the regulation of mitochondrial CPT synthesis and activities in the heart.

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Soran, Handrean, et Naveed Younis. « Insulin detemir : a new basal insulin analogue ». Diabetes, Obesity and Metabolism 8, n^o 1 (janvier 2006) : 26–30. http://dx.doi.org/10.1111/j.1463-1326.2005.00487.x.

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Goldman-Levine, Jennifer D., Dhiren K. Patel et David M. Schnee. « Insulin Degludec : A Novel Basal Insulin Analogue ». Annals of Pharmacotherapy 47, n^o 2 (février 2013) : 269–77. http://dx.doi.org/10.1345/aph.1r351.

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Younis, N. « Insulin glargine : a new basal insulin analogue ». QJM 95, n^o 11 (1 novembre 2002) : 757–61. http://dx.doi.org/10.1093/qjmed/95.11.757.

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Gale, Edwin AM. « Insulin lispro:a new quick-acting insulin analogue ». Expert Opinion on Investigational Drugs 6, n^o 9 (septembre 1997) : 1247–56. http://dx.doi.org/10.1517/13543784.6.9.1247.

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Plavsic, Ljiljana, Katarina Mitrovic, Sladjana Todorovic, Rade Vukovic, Tatjana Milenkovic et Dragan Zdravkovic. « Glycaemic control and prevalence of hypoglycaemic events in children and adolescents with type 1 diabetes mellitus treated with insulin analogues ». Vojnosanitetski pregled 71, n^o 9 (2014) : 817–20. http://dx.doi.org/10.2298/vsp130422039p.

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Background/Aim. An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurrence of hypoglycaemic episodes in children and adolescents with T1DM. Methods. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.3%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months. Results. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.24%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001). Conclusion. Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.

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Hashim, Noor Wafaa, Kadhim Ali Ali et Abbas Mahdi Rahmah. « Comparative Study between the Glycemic Control of Human Insulin and Insulin analogue In Sample of Iraqi Type 1 Diabetic Children and Adolescents ». Al Mustansiriyah Journal of Pharmaceutical Sciences 18, n^o 2 (1 décembre 2018) : 100–104. http://dx.doi.org/10.32947/ajps.v18i2.482.

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Insulin analogue introduced to offer insulin replacement therapy mimic to normal human physiology. The aim of this study is to compare between the glycemic control of insulin analogue and conventional human insulin in a sample of type 1 diabetic Iraqi children and adolescents. Forty type 1 diabetic Iraqi children and adolescents age between (6-18) years enrolled in this study and divided into two groups. Group 1 contains 20 patients switched from human insulin to insulin analogue. Group 2 contain 20 patients continued with conventional human insulin. The results showed that both therapies reduced fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c %) but insulin analogue treated group had highly significant reduction. Both therapies did not affect on blood urea nitrogen and serum creatinine. Human insulin reduced triglyceride (TG) and very low-density lipoprotein (VLDL) significantly. The parameters measures at baseline and after three months of treatments. In conclusion insulin analogue is superior over conventional human insulin in reducing glycemic indices in a sample of type 1 diabetic Iraqi children and adolescents.

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Jarosinski, Mark A., Yen-Shan Chen, Nicolás Varas, Balamurugan Dhayalan, Deepak Chatterjee et Michael A. Weiss. « New Horizons : Next-Generation Insulin Analogues : Structural Principles and Clinical Goals ». Journal of Clinical Endocrinology & ; Metabolism 107, n^o 4 (24 novembre 2021) : 909–28. http://dx.doi.org/10.1210/clinem/dgab849.

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Abstract Design of “first-generation” insulin analogues over the past 3 decades has provided pharmaceutical formulations with tailored pharmacokinetic (PK) and pharmacodynamic (PD) properties. Application of a molecular tool kit—integrating protein sequence, chemical modification, and formulation—has thus led to improved prandial and basal formulations for the treatment of diabetes mellitus. Although PK/PD changes were modest in relation to prior formulations of human and animal insulins, significant clinical advantages in efficacy (mean glycemia) and safety (rates of hypoglycemia) were obtained. Continuing innovation is providing further improvements to achieve ultrarapid and ultrabasal analogue formulations in an effort to reduce glycemic variability and optimize time in range. Beyond such PK/PD metrics, next-generation insulin analogues seek to exploit therapeutic mechanisms: glucose-responsive (“smart”) analogues, pathway-specific (“biased”) analogues, and organ-targeted analogues. Smart insulin analogues and delivery systems promise to mitigate hypoglycemic risk, a critical barrier to glycemic control, whereas biased and organ-targeted insulin analogues may better recapitulate physiologic hormonal regulation. In each therapeutic class considerations of cost and stability will affect use and global distribution. This review highlights structural principles underlying next-generation design efforts, their respective biological rationale, and potential clinical applications.

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Hansen, B. F., P. Kurtzhals, A. B. Jensen, A. Dejgaard et D. Russell-Jones. « Insulin X10 revisited : a super-mitogenic insulin analogue ». Diabetologia 54, n^o 9 (3 juin 2011) : 2226–31. http://dx.doi.org/10.1007/s00125-011-2203-8.

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Narendran, Parth. « Insulin glulisine : a new rapid-acting insulin analogue ». Prescriber 17, n^o 14 (19 juillet 2006) : 23–29. http://dx.doi.org/10.1002/psb.400.

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Balos, Ljiljana, Silvija Sajic et Vera Zdravkovic. « Elements of metabolic control in children with type 1 diabetes before and after introduction to insulin analogues ». Srpski arhiv za celokupno lekarstvo 139, n^o 9-10 (2011) : 605–9. http://dx.doi.org/10.2298/sarh1110605b.

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Introduction. Diabetes mellitus type 1 (T1DM) in children is characterized by unstable course. A significant number of studies shows that introduction to insulin analogues treatment aims towards better control of the disease. Objective. The assessment of metabolic control in children with T1DM that were introduced to insulin analogue treatment after many years of treatment with classic (human) insulin. Methods. The study included 59 patients 2-19 years old (12.9?3.8) with T1DM, transferred from treatment with human insulin to insulin analogues treatment. Data were obtained directly from patients and their parents, as well as from medical records. Results. The introduction to insulin analogues treatment, leads to a decrease in the value of glycolized haemoglobin (HbA1c) after 6 months (9.27?1.68% vs 8.63?1:26%, p=0.06). Average daily dose of insulin expressed per IU/kg of classic and insulin analogue (1.04?0.38 vs 1.03?0.30; p>0.05), remained almost the same. In 39 examinees (66.1%), 6 months before the introduction to insulin analogue treatment, severe hypoglicemia was registered and 6 months after the introduction to insulin analogue treatment it appeared in only two examinees (3.4%) (p<0.001). Ketoacidosis, 6 months before introduction to insulin analogues treatment, appeared in 16 examinees (27.1%), while 6 months after it was not registered (p<0.001). Conclusion. The use of insulin analogue treatment in childhood provides adequate metabolic control and substantially reduces the risk of acute complications (severe hypoglicemia, ketoacidosis).

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Sudár, Zsolt, Lajos Muth, Csaba Nyirati, Vince Szí, János Tornóczky et Gabriella Ulrich. « Clinical experiences with basal analogue insulin in routine care. Retrospective follow up analysis of a database from daily routine care ». Orvosi Hetilap 154, n^o 37 (septembre 2013) : 1476–84. http://dx.doi.org/10.1556/oh.2013.29703.

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Introduction: Basal-bolus insulin regime is frequently used in type 2 diabetes in order to improve metabolic control and decrease the risk of complications. A general question is, however, the effect of application of analogue insulin in comparison to human insulin regimes. Aim: The aim of the authors was to perform a retrospective database analysis among patients who were switched from human insulin only based basal-bolus regime to analogue only insulin regime in order to examine changes in metabolic control, body weight, insulin dose and basal:bolus insulin ratio. Method: Type 2 diabetic patients (n = 137) were enrolled who used once daily basal insulin with complementary bolus insulin given at main meals, and human insulin was switched to analogue insulin. Patients were divided into two groups using detemir (n = 103) or glargine (n = 34). Results: During 17 months ofanalogue insulin treatment the HbA1c was decreased by 0.34% (detemir –0.44%; glargine –0.17%). Body weight was increased by 1.11 kg (detemir +1.0 kg; glargine +1.43 kg). The basal:bolus insulin ratio increased in all groups (entire cohort 6.04%, detemir 5.26%, glargine 8.37%). The average insulin dose was 80.76 units at the end of follow up. There was no significant difference in terms of total and basal insulin doses between detemir (27.89 and 79.78 U, respectively) and glargine group (32.85 and 83.74 U, respectively). Conclusions: These results support that switching from human to analogue insulin in basal-bolus regime could improve the metabolic control by increasing dose of basal analogue insulin and basal: bolus ratio. Both detemir and glargine can provide similar improvement in metabolic control with the same insulin dose but with relatively more weight gain with glargine. Orv. Hetil., 2013, 154, 1476–1484.

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erf. « Zulassungserweiterung : GLP1-Analogon plus Insulin ». Der Hausarzt 49, n^o 3 (février 2012) : 81. http://dx.doi.org/10.1007/s15200-012-0157-7.

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Colquitt, J., P. Royle et N. Waugh. « Are analogue insulins better than soluble in continuous subcutaneous insulin infusion ? Results of a meta-analysis ». Diabetic Medicine 20, n^o 10 (octobre 2003) : 863–66. http://dx.doi.org/10.1046/j.1464-5491.2003.01018.x.

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Caparrotta, T. M., et M. Evans. « PEGylated insulin Lispro, (LY2605541)-a new basal insulin analogue ». Diabetes, Obesity and Metabolism 16, n^o 5 (12 septembre 2013) : 388–95. http://dx.doi.org/10.1111/dom.12196.

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Gammeltoft, Steen, Bo Falck Hansen, Lars Dideriksen, Anders Lindholm, Lauge Schäffer, Thomas Trüb, Anthony Dayan et Peter Kurtzhals. « Insulin aspart : a novel rapid-acting human insulin analogue ». Expert Opinion on Investigational Drugs 8, n^o 9 (septembre 1999) : 1431–42. http://dx.doi.org/10.1517/13543784.8.9.1431.

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Venkatachalam, Hariharan. « Use of Fast-Acting Insulin Analog for Preparing a Pharmaceutical Composition for Preventing, Treating, or Alleviating Diabetes ». Technoarete Transactions on Recent Research in Applied Microbiology and Biotechnology 1, n^o 1 (3 mars 2022) : 21–24. http://dx.doi.org/10.36647/ttrramb/01.01.a005.

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Diabetes is the most common disease in India that mostly affects adult people and reduces physical strength. Diabetes decreases insulin production in the human body that creates various physical disturbances such as damage to the heart, stroke, and others. In the past decades, medical treatments have followed long-acting insulin that reduces life expectancy rate and increases mortality rate in India. Along with that, in the present time, India's medical treatment has adopted the pharmaceutical composition of insulin to prevent diabetes and manage blood sugar in the human body. In this regard, this research study has selected some previous research papers to understand the importance of fast-acting insulin analogue to prevent diabetes. According to the secondary information, most of the medical treatment process in India has adopted fast-acting insulin analogue to prevent diabetes. Moreover, though fast-acting insulin analogue India reduces mortality rate and increases the life expectancy of adult people in India. Keyword : Metabolic disturbances, E-bacteria, amino acids, Regular Human Insulin (RHI).

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&NA;. « Insulin analogue : achieves more physiological levels of plasma insulin than soluble insulin ». Inpharma Weekly &NA;, n^o 726 (mars 1990) : 6–7. http://dx.doi.org/10.2165/00128413-199007260-00010.

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Girsh, Ya V., et Z. A. Akhmedova. « Hypersensitivity Reaction to Insulin Detemir in a Paediatric Patient Taking Basal-Bolus Therapy ». Doctor.Ru 19, n^o 10 (2020) : 69–73. http://dx.doi.org/10.31550/1727-2378-2020-19-10-69-73.

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Objective: To present a case study demonstrating an atypic side effect of insulin — hepersensitivity reaction to insulin detemir, a long-term human insulin analogues. Key Points. At the inpatient paediatric unit, we had an 11-year old girl with symptoms and clinical signs of diabetes mellitus (DM). Following physical examination, the patient was diagnosed with type 1 diabetes (manifestation). She was prescribed intensified basal-bolus therapy with insulin analogues: insulin detemir and insulin aspart. On day 5, the patient developed a hypersensitivity reaction in the site of insulin detemir injections. Replacement of insulin detemir with insulin degludec resolved the allergic reaction. Conclusion. We described a case of a hypersensitivity reaction to intensified insulin therapy with basal insulin analogue detemir. Hypersensitivity reactions to insulin analogues are rare; however they can be life-threatening. The primary management is the use of another insulin analogue. Keywords: diabetes mellitus, allergy, insulin detemir, insulin degludec.

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Mao, Ruifeng, Yingying Chen, Zhenjing Chi et Yefu Wang. « Insulin and its single-chain analogue ». Applied Microbiology and Biotechnology 103, n^o 21-22 (21 octobre 2019) : 8737–51. http://dx.doi.org/10.1007/s00253-019-10170-0.

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Dedov, Ivan Ivanovich, et Marina Vladimirovna Shestakova. « Insulin degludec is a new ultra-long-acting insulin analogue ». Diabetes mellitus 17, n^o 2 (3 juin 2014) : 91–104. http://dx.doi.org/10.14341/dm2014291-104.

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Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba?) is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more) non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

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HUANG, YuPu, Qin ZHANG, LanXin WANG et Wei CHEN. « A new generation ultra-long-acting insulin analogue-insulin degludec ». Pharmaceutical Care and Research 13, n^o 1 (28 février 2013) : 6–8. http://dx.doi.org/10.5428/pcar20130103.

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Home, Philip D., et Simon G. Ashwell. « Insulin glargine : the first clinically useful extended-action insulin analogue ». Expert Opinion on Pharmacotherapy 2, n^o 11 (novembre 2001) : 1891–902. http://dx.doi.org/10.1517/14656566.2.11.1891.

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Am Gale, Edwin. « Insulin lispro : The first insulin analogue to reach the market ». Practical Diabetes International 13, n^o 4 (juillet 1996) : 122–24. http://dx.doi.org/10.1002/pdi.1960130409.

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