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1
Valenzano, M. "Insulin: 100 years but not over the hill! A treatment with potential for renewal." Journal of AMD 25, no. 2 (July 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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Monda, V. M. "Association of GLP-1 RA once weekly and basal insulin: a valid therapeutic option from the complications of SARS-CoV-2 infection too?" Journal of AMD 24, no. 4 (February 2022): 295. http://dx.doi.org/10.36171/jamd21.24.4.5.
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Gli agonisti recettoriali del glucagon like peptide-1 (GLP1-RAs) sono un gruppo di farmaci antidiabetici con una rilevante azione sul controllo glicemico, basata sull’aumento della secrezione di insulina glucosio-dipendente con concomitante riduzione della secrezione di glucagone e ritardato svuotamento gastrico. I GLP1-RA hanno inoltre attività pleiotropiche come proprietà antinfiammatorie, antitrombotiche e antiobesogeniche, con evidenti benefici su eventi cardiovascolari maggiori, mortalità cardiovascolare e danno renale. Tutto ciò rende questa classe di farmaci un elemento chiave nella gestione dei pazienti con diabete tipo 2 e potenzialmente utile nei soggetti con COVID-19 (2019nCoV – Coronavirus disease 2019, COVID-19). Per le proprietà antinfiammatorie è stato ipotizzato che le terapie a base di incretino-mimetici esercitino effetti benefici sugli esiti di COVID-19. Qui riportiamo un caso di una donna di 82 anni con diabete tipo 2 scarsamente controllato, che utilizzava un regime insulinico basal-bolus più metformina. Il miglioramento del controllo glicemico ottenuto passando dal trattamento con insulina basale al GLP-1RA aggiunto al regime insulinico basale, con la sospensione dell’insulina prandiale (trattamento di de-escalation) in questo caso è risultato associato agli effetti benefici sugli esiti di COVID-19. PAROLE CHIAVE GLP1-RAs; DMT2; SARS-CoV-2; COVID-19.
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Giorgino, Francesco, Sergio Di Molfetta, and Irene Caruso. "Gestione iniziale della terapia con insulina basale nel paziente diabetico." L'Endocrinologo 21, no. 5 (October 2020): 370–72. http://dx.doi.org/10.1007/s40619-020-00780-6.
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Jermendy, György. "Intensive conservative insulin treatment in patients with type 2 diabetes mellitus." Orvosi Hetilap 153, no. 38 (September 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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Goldman, Jennifer, and John R. White. "Advances in Basal Insulin Therapy." Journal of Pharmacy Technology 32, no. 6 (September 22, 2016): 260–68. http://dx.doi.org/10.1177/8755122516667128.
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Objective: To review 2 new basal insulin analogs that have been approved in the United States for use in type 1 and type 2 diabetes—insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL. Data Sources: PubMed was searched using the terms “insulin glargine 300 units/mL,” “Gla-300,” “insulin degludec,” “IDeg,” “insulin degludec 200 units/mL,” and “insulin degludec 100 units/mL” for articles published between 1995 and May 2016. Study Selection and Data Extraction: Clinical trials, meta-analyses and subanalyses were identified; review articles were excluded. Relevant citations from identified articles were also reviewed. Data Synthesis: The new basal insulins, insulin glargine 300 units/mL and insulin degludec 100 units/mL and 200 units/mL, have improved pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 units/mL. All demonstrate longer durations of action, beyond 24 hours, and less variability. These improved profiles translate into comparable A1C reductions and comparable, or improved, levels of hypoglycemia compared to insulin glargine 100 units/mL. Conclusions: These benefits may lead to improved glycemic control in a range of patients with type 1 and type 2 diabetes with true once-daily dosing.
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Demidova, Tatiana Y., and Olga V. Balutina. "Special aspects of concentrated insulins: basic characteristics and research findings." Diabetes mellitus 22, no. 5 (January 17, 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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Inman, Taylor R., Erika Plyushko, Nicholas P. Austin, and Jeremy L. Johnson. "The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes." Therapeutic Advances in Endocrinology and Metabolism 9, no. 5 (April 23, 2018): 151–55. http://dx.doi.org/10.1177/2042018818763698.
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The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen-injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen-injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications.
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Dzhavakhishvili, T. S., T. I. Romantsova, and 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, no. 1 (March 15, 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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Liebl, Andreas. "Praktische Umsetzung einer Insulintherapie bei Typ-2-Diabetes." Diabetes aktuell 19, no. 05 (September 2021): 204–12. http://dx.doi.org/10.1055/a-1576-9316.
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ZUSAMMENFASSUNGIn Deutschland sind eine Vielzahl basaler und prandialer Insuline auf dem Markt, die sich erheblich in ihrer Pharmakokinetik und in ihrem Einsatzbereich unterscheiden. Der Start einer Insulintherapie bei Typ-2-Diabetes erfolgt im Allgemeinen in Form einer basalunterstützten oralen Therapie (BOT). Moderne, lang und gleichmäßig wirksame Insulinanaloga verringern das Hypoglykämierisiko und erlauben eine freie Wahl des Injektionszeitpunkts. Absolut entscheidend für das Gelingen ist die konsequente Titration der Dosis. Eine basale Überinsulinisierung ist dabei unbedingt zu vermeiden. In einem späteren Schritt kann die schrittweise Zugabe von prandialem Insulin erfolgen. Das Zählen von Broteinheiten (BEs) zur Insulindosisanpassung ist bei Typ-2-Diabetes fast nie sinnvoll. Die häufigsten Probleme bei der Insulintherapie sind Hypoglykämien, Gewichtszunahme, initiale Sehstörungen sowie schwer beherrschbare Insulinresistenzen. Für all diese Probleme gibt es erprobte Strategien und zahlreiche Tipps und Tricks, die im Einzelfall zu erstaunlichen Erfolgen führen können.
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Levien, Terri L., Danial E. Baker, John R. White, and R. Keith Campbell. "Insulin Glargine: A New Basal Insulin." Annals of Pharmacotherapy 36, no. 6 (June 2002): 1019–27. http://dx.doi.org/10.1345/aph.1a301.
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OBJECTIVE: To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine. DATA SOURCES: Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966–July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995–July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information. STUDY SELECTION AND DATA EXTRACTION: All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature. DATA SYNTHESIS: Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies. CONCLUSIONS: Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.
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Fadini, Gian Paolo, Michael Feher, Troels Krarup Hansen, Harold W. de Valk, Mette Marie Koefoed, Michael Wolden, Esther Zimmermann, and Johan Jendle. "Switching to Degludec From Other Basal Insulins Is Associated With Reduced Hypoglycemia Rates: A Prospective Study." Journal of Clinical Endocrinology & Metabolism 104, no. 12 (August 9, 2019): 5977–90. http://dx.doi.org/10.1210/jc.2019-01021.
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Abstract Context Observational studies of insulin degludec (degludec) with hypoglycemia events prospectively recorded are lacking. Objective To evaluate the safety and effectiveness of degludec in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) switching from other basal insulins in routine care. Design Results From Real-World Clinical Treatment With Tresiba® was a multinational, multicenter, prospective, observational, single-arm study comprising a 4-week baseline period (preswitch basal insulin) and 12-month follow-up (degludec). Setting Routine clinical practice. Patients or Other Participants Insulin-treated patients (≥18 years) with T1D (n = 556) or T2D (n = 611) with treatment plans to initiate degludec. Interventions Switching to degludec from other basal insulins. Main Outcome Measure Change from baseline in number of overall hypoglycemic events recorded in patient diaries. Results In T1D, the 12-month follow-up/baseline rate ratios (95% CI) of overall [0.80 (0.74 to 0.88)], nonsevere [0.83 (0.76 to 0.91)], severe [0.28 (0.14 to 0.56)], and nocturnal [0.61 (0.50 to 0.73)] hypoglycemia suggested significantly lower hypoglycemia rates with degludec (all Ps < 0.001). At 12 months, HbA1c, fasting plasma glucose (FPG), and basal insulin dosage decreased significantly. Body weight increased, and treatment satisfaction improved significantly. In T2D, the hypoglycemia rate ratios were overall [0.46 (0.38 to 0.56)], nonsevere [0.53 (0.44 to 0.64)], and nocturnal [0.35 (0.20 to 0.62)] (all Ps < 0.001; too few events for analysis of severe hypoglycemia). At 12 months, HbA1c and FPG decreased significantly. Body weight and insulin dosages remained unchanged, and treatment satisfaction was significantly improved. Conclusions In a routine clinical care setting, switching to degludec from other basal insulins was associated with significantly lower rates of hypoglycemia, improved glycemic control, and treatment satisfaction in patients with T1D or T2D.
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J, Fövényi, Pánczél P, and 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, no. 1 (January 2, 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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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder, and 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, no. 4 (August 28, 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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Ortiz-Roa, Cynthia, and Análida Elizabeth Pinilla-Roa. "Efecto de la lipohipertrofia en el control metabólico de pacientes con diabetes mellitus tipo 2." Revista de la Facultad de Medicina 65, no. 4 (October 1, 2017): 697–701. http://dx.doi.org/10.15446/revfacmed.v65n4.53108.
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La lipodistrofia (lipohipertrofia, lipoatrofia) es una complicación dada por la técnica inadecuada de inyección subcutánea de insulina. Se presenta el caso de una paciente de 46 años con diabetes mellitus tipo 2 descontrolada, en tratamiento con insulina glargina 45UI/día, sin control glucométrico y con múltiples ajustes y hospitalizaciones. Al ingreso, el automonitoreo muestra glucometrías basales y posprandiales fuera de metas, glucemia basal de 299 mg/dL y HbA1c de 11%. Al interrogatorio, se evidencian fallas en la técnica de aplicación de insulina, en particular falta de rotación del sitio de aplicación. En el examen físico se encuentra lipohipertrofia dada por panículo adiposo infraumbilical prominente bilateral e induración del tejido celular subcutáneo; en ecografía se visualiza infiltración grasa de rectos anteriores. Se da instrucción a la paciente sobre la correcta técnica de aplicación de insulina con rotación diaria del sitio de aplicación, descanso de zonas con lipohipertrofia y guía para automonitoreo.El automonitoreo en los 10 primeros días mostró mejoría de glucometrías basales hasta 116 mg/dL y valor limítrofe de 75 mg/dL, comparados con promedio de glucometría basal previa de 242 mg/dL con la misma insulina y dosis. Se hizo seguimiento estrecho para definir dosis requerida de insulina y vigilar posible hipoglucemia, con mejoría en la HbA1c de 9.2% y 8.8% a los 4 y 11 meses, respectivamente.
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Buryukova, Elena V., Abdul Jabbar, and Svetlana V. Elizarova. "When basal insulin is not enough: successful strategies for insulin intensification in patients with type 2 diabetes mellitus." Diabetes mellitus 20, no. 5 (December 13, 2017): 363–73. http://dx.doi.org/10.14341/dm8824.
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Maintaining glycemic control through intensive clinical management of patients with type 2 diabetes mellitus (T2DM) is well recognized to reduce the risk of diabetes-associated complications. Patients in Russia have high rates of microvascular and macrovascular complications as a result of undiagnosed, untreated, or inadequately treated diabetes, emphasizing the need for better clinical management. The introduction of basal insulin therapy is often necessary for patients with T2DM when oral antihyperglycemic drugs and lifestyle management strategies are no longer effective inmaintaining glycemic targets. However, after initiation of insulin, patients often remain on basal insulin for long periods despite suboptimal glycemic control, and intensification of insulin therapy is frequently necessary. Here, we report on several different insulin intensification strategies available to clinicians and their patients to improve glycemic control and the advantages and disadvantages of each approach. These strategies include the use of short- and long-acting insulins administered either as bolus doses or as premixed insulins. When selecting the most appropriate intensification strategy, clinicians should consider the lifestyle and treatment goals of their patients to help ensure treatment success.
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Dzhavakhishvili, T. Sh, T. I. Romantsova, and O. V. Roik. "Dinamika massy tela u bol'nykh sakharnymdiabetom 2 tipa v techenie pervogo godainsulinoterapii." Obesity and metabolism 7, no. 4 (December 15, 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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Bereda, Gudisa. "Role of Insulin: Perspectives." Diabetes and Islet Biology 5, no. 1 (January 11, 2022): 01–06. http://dx.doi.org/10.31579/2641-8975/030.
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The pancreas in a non-diabetic patient invariably produces a lesser quantum of insulin (basal production). Insulin furnishes glucose homeostasis by keeping the plasma glucose worth in an optimum class throughout the day. It assists transport blood glucose into the body cells where the glucose is metabolized to generate energy. Regular insulin is inserted pre-meal to abrupt the postprandial ascend in glucose levels. It figures hexamers after insertion into the subcutaneous space sluggishing its absorption. Ultra-fast acting commences to act 4-7 minutes before regular apidra and lasts for around 3 hours. The absorption rate of lente insulin is downgraded by the extension of zinc to the insulin preparation. Long-acting insulins furnish basal insulin coverage. Atrophy of subcutaneous fat owing to applicability of further greater accumulated insulin preparations of neutral potenz hydrogen.
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Cheung, J. Y., J. M. Constantine, and J. V. Bonventre. "Cytosolic free calcium concentration and glucose transport in isolated cardiac myocytes." American Journal of Physiology-Cell Physiology 252, no. 2 (February 1, 1987): C163—C172. http://dx.doi.org/10.1152/ajpcell.1987.252.2.c163.
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The role of cytosolic free Ca2+ concentration, [Cai], in mediating insulin's stimulatory effect on glucose transport was investigated in isolated Ca2+-tolerant rat ventricular cells. Approximately 98% of glucose transport in isolated myocytes was inhibited by phloretin. Insulin-accelerated glucose transport by 50-115% over basal transport rate. Removal of extracellular Ca2+ had no effect on either the basal transport rate or insulin's stimulatory action, indicating that extracellular Ca2+ was not necessary for insulin's effect to be manifest. Addition of A23187 had no effect on glucose transport rate. Under basal conditions, [Cai] was 167 +/- 12 nM as measured by fura-2 fluorescence and 239 +/- 22 nM by null-point titration with arsenazo III. Loading cells with fura-2 did not affect basal glucose transport rates. In addition, the stimulatory effect of insulin on glucose transport was preserved in fura-2 loaded cells. In paired experiments, insulin did not increase [Cai] as measured by fura-2 fluorescence or null-point titration despite acceleration of glucose transport. In contrast, addition of KCl (40 mM) increased [Cai] from 168 +/- 30 to 287 +/- 51 nM and resulted in 50% reduction in glucose transport rate. In other experiments designed to control for the hyperosmolar effects of KCl, NaCl (40 mM) caused no change in [Cai] but also inhibited glucose transport rate by 50%. We conclude that an elevation in [Cai] is unlikely to be the intracellular signal mediating insulin's effect on glucose transport since insulin's stimulatory effect was not reduced by Ca2+ -free media, insulin had no detectable effect on [Cai], and elevation of [Cai] by KCl did not result in stimulation of glucose transport.
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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder, and 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, no. 3 (July 12, 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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Hirsch, Irl B., Rattan Juneja, John M. Beals, Caryl J. Antalis, and Eugene E. Wright. "The Evolution of Insulin and How it Informs Therapy and Treatment Choices." Endocrine Reviews 41, no. 5 (May 12, 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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Davis, T. A., and I. E. Karl. "Resistance of protein and glucose metabolism to insulin in denervated rat muscle." Biochemical Journal 254, no. 3 (September 15, 1988): 667–75. http://dx.doi.org/10.1042/bj2540667.
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Denervated (1-10 days) rat epitrochlearis muscles were isolated, and basal and insulin-stimulated protein and glucose metabolism were studied. Although basal rates of glycolysis and glucose transport were increased in 1-10-day-denervated muscles, basal glycogen-synthesis rates were unaltered and glycogen concentrations were decreased. Basal rates of protein degradation and synthesis were increased in 1-10-day-denervated muscles. The increase in degradation was greater than that in synthesis, resulting in muscle atrophy. Increased rates of proteolysis and glycolysis were accompanied by elevated release rates of leucine, alanine, glutamate, pyruvate and lactate from 3-10-day-denervated muscles. ATP and phosphocreatine were decreased in 3-10-day-denervated muscles. Insulin resistance of glycogen synthesis occurred in 1-10-day denervated muscles. Insulin-stimulated glycolysis and glucose transport were inhibited by day 3 of denervation, and recovered by day 10. Inhibition of insulin-stimulated protein synthesis was observed only in 3-day-denervated muscles, whereas regulation by insulin of net proteolysis was unaffected in 1-10-day-denervated muscles. Thus the results demonstrate enhanced glycolysis, proteolysis and protein synthesis, and decreased energy stores, in denervated muscle. They further suggest a defect in insulin's action on protein synthesis in denervated muscles as well as on glucose metabolism. However, the lack of concurrent changes in all insulin-sensitive pathways and the absence of insulin-resistance for proteolysis suggest multiple and specific cellular defects in insulin's action in denervated muscle.
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Moyers, Julie S., Ryan J. Hansen, Jonathan W. Day, Craig D. Dickinson, Chen Zhang, Steven D. Kahl, Xiaoping Ruan, et al. "Preclinical Characterization of Once Weekly Basal Insulin Fc (BIF)." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A442. http://dx.doi.org/10.1210/jendso/bvab048.903.
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Abstract Weekly basal insulin injections may increase treatment adherence in subjects with diabetes and an appropriately engineered weekly basal insulin may reduce daily pharmacokinetic (PK)/pharmacodynamic (PD) fluctuations compared to currently available daily basal insulins. Therefore, a weekly insulin has the potential to not only ease the burden of insulin therapy, but also improve outcomes for subjects with diabetes in a real-world setting. Basal insulin Fc (BIF, LY3209590) is an insulin Fc-fusion protein in clinical testing as a once weekly treatment for type 1 and type 2 diabetes mellitus (T1DM, T2DM). BIF is comprised of a human single-chain insulin fused to a human IgG2 Fc domain through a peptide linker. The in vitro evaluation determined that BIF exhibited reduced insulin receptor (IR) potency with full agonism, selectivity against human insulin-like growth factor-1 receptor (hIGF-1R), and functional properties similar to native human insulin. The binding affinity of BIF for hIR isoform A, Ki = 25 nM (SEM = 4, n=10), and hIR isoform B, Ki = 26 nM (SEM = 4, n=10), was more than two orders of magnitude weaker than human insulin. BIF stimulated IR phosphorylation in cells with reduced potency, but full agonism, and showed a significantly faster hIR dephosphorylation profile than either human insulin or AspB10 insulin. BIF stimulated de novo lipogenesis in 3T3-L1 adipocytes and cell proliferation in SAOS-2 and H4IIE cells with at least a 70-fold reduction in potency compared to human insulin. BIF possessed markedly reduced binding and activation of hIGF-1R making definitive mitogenic measurements unattainable. In preclinical in vivo pharmacology studies using streptozotocin (STZ)-treated diabetic rats, a statistically significant decrease in blood glucose compared to vehicle-treated animals was seen 24 hours post-injection and persisted through 336 hours post-injection following a single subcutaneous administration (30 nmol/kg) of BIF. In STZ-treated rats, BIF reached a Tmax at 48 hours, possessed an apparent clearance rate of ~0.85 mL/hr/kg, and t1/2 of ~120 hrs. Collectively, these results demonstrate that BIF possesses selective IR agonism with a pharmacological profile similar to native insulin, however with a significantly reduced potency, and a significantly extended time action profile in preclinical animal models supporting once weekly testing in the clinic.
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Galstyan, Gagik Radikovich. "National advisory board on diabetes mellitus: unsolved issues and new opportunities for diabetes treatment." Diabetes mellitus 17, no. 3 (August 13, 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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Pires, Antonio Carlos, and Antonio Roberto Chacra. "A evolução da insulinoterapia no diabetes melito tipo 1." Arquivos Brasileiros de Endocrinologia & Metabologia 52, no. 2 (March 2008): 268–78. http://dx.doi.org/10.1590/s0004-27302008000200014.
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A descoberta da insulina foi o grande marco da história do diabetes melito e a grande conquista para o seu tratamento. A primeira insulina disponibilizada foi a regular. Na seqüência, Hagedorn acrescentou a protamina à insulina, criando, assim, a insulina NPH. Na década de 1950 foi sintetizada uma insulina desprovida de protamina, denominada insulina lenta. Com o advento da biologia molecular, sintetizou-se, via DNA recombinante, a insulina humana sintética. Mais recentemente, foram disponibilizados vários tipos de análogos de insulina que permitiram o melhor controle metabólico dos pacientes. O tratamento do diabetes melito tipo 1, além do processo educacional, incluindo a prática regular de atividades físicas e orientações dietéticas, resume-se na substituição plena de insulina de longa e curta durações de ação, de maneira individualizada, de acordo com a experiência do médico-assistente. No diabetes melito tipo 1, a preferência é pelas insulinas de menor variabilidade, por meio do esquema basal/bólus ou pelas bombas de infusão contínua de insulina subcutânea com o objetivo de mimetizar a liberação fisiológica de insulina pelas células-beta.
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Sultan, Muhammad H., Wael A. Mahdi, and Young M. Kwon. "Insulin Release from NPH Insulin-Loaded Pluronic® F127 Hydrogel in the Presence of Simulated Tissue Enzyme Activity." Processes 8, no. 10 (October 21, 2020): 1320. http://dx.doi.org/10.3390/pr8101320.
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Background: Despite the widespread use of newer basal insulins, Natural Protamine Hagedorn (NPH) insulin still represents a well-established basal formulation with its long history of use, featuring the native form of human insulin. However, NPH insulin exhibits an undesirable peak within hours after a single subcutaneous (s.c.) injection, which may lead to hypoglycemia followed by insufficient basal insulin delivery. This may be attributed to the s.c. enzyme activities degrading the protamine in NPH microcrystals. Methods: A thermogelling block copolymer Pluronic® F127 (PF127) was utilized as a protective carrier for NPH microcrystals and as a modulator for insulin release from NPH. NPH insulin-loaded PF127 gel was prepared with varying concentrations of the polymer (15–25%) under mild conditions. The formulations were characterized for their gelling temperature, morphology, gel erosion, and in vitro insulin release, with trypsin concentrations up to 5 U/mL. Results: Scanning electron microscopy (SEM) showed that the integrity of NPH microcrystals was maintained after preparation. The burst release of insulin from NPH was significantly attenuated over the course of ~16h in the presence of PF127 with or without enzyme activity. Conclusion: NPH-PF127 successfully resisted the acceleration of NPH crystal dissolution and insulin release in vitro in the presence of protamine-degrading enzyme activity, warranting further testing.
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Ferencz, Viktória, Beatrix Domján, László Gerő, Tímea Tänczer, and Gy Ádám Tabák. "A normoglykaemia elérésének korlátai inzulinkezelt 2-es típusú cukorbetegekben." Orvosi Hetilap 156, no. 36 (September 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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Becker, Reinhard H. A. "Insulin Glulisine Complementing Basal Insulins: A Review of Structure and Activity." Diabetes Technology & Therapeutics 9, no. 1 (February 2007): 109–21. http://dx.doi.org/10.1089/dia.2006.0035.
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Ponzani, P. "Insulin DEgludec in hospitalized patients with type 2 diabetes (IDEOS Study): what effects on glycemic control, glycemic variability and hypoglycemia." Journal of AMD 23, no. 3 (November 2020): 170. http://dx.doi.org/10.36171/jamd20.23.3.2.
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Modern guidelines suggest the control of hyperglycemia in hospitalized patients through insulin therapy and the achievement of individualized glycemic targets, avoiding hypoglycemia, associated with a worsening of outcomes and a mortality increase. There is little evidence in literature on the use of new basal insulins in a hospital setting. OBJECTIVE OF THE STUDY Document, in real life context, the use of insulin degludec and the results in terms of glycemic control, variability and hypoglycemia in hospitalized patients with type 2 diabetes, com pared to a population treated with traditional basal insulins. DESIGN AND METHODS Prospective observational study on patients hospitalized in internist area. Personal and clinical data, in particular capillary blood levels on 4 daily points and hypoglycemia were collect ed. In a group of patients on traditional basal insulin therapy not at tar get, a switch to insulin degludec was performed. RESULTS 65 patients (58.5% male) were enrolled: age 70.8±10.7 years, BMI 27.7 ± 4.4, HbA1c 8.4 ± 1.3% (average+/SD). 76.4% of patients had 3 or more comorbidities. 69.2% of patients were treated with basalbolus, 7.7% with basalplus, 16.9% with basal insulin alone. In the group treated with degludec (35 patients), a significant reduction in mean capillary glycaemia was obtained between the first day of hospitaliza tion or initiation of therapy and discharge in each time slot: 36.6 mg /dl fasting (p <0.0001), 30 mg/dl before lunch (p <0.005), 38.9 mg/dl before dinner (p <0.001) and 37.3 mg/dl bedtime (p <0.001) and also fewer hypoglycemia (20% had at least one daytime hypoglycemia, no subjects had nocturnal hypoglycaemia). In the group receiving insulin glargine for the entire period (30 patients), a significant reduction in capillary blood sugar levels is present only in the pre lunch range (43.8 mg / dl, p <0.001) and 26% of subjects had at least one daytime hypoglycemia and 2% nocturnal hypoglycemia. In the group switched to degludec, the mean capillary fasting blood glucose decreased from 176.6 ± 27.9 to 130.4 ± 36.6 mg/dl, that of predinner from 217.9 ± 36.7 to 170.9 ± 49.1 mg/dl, patients at target upon awakening increased from 10% to 65%, glycemic variability expressed as the mean of morning standard deviations fell from 45.2 to 25.6 and hypoglycemia decreased (% of patients with at least one daytime hypoglycemia from 25% to 15%, with nocturnal hypoglycemia from 5% to 0%). Conclusions The use of insulin degludec in hospitalized patients in medical area was effective and safe, with better glycemic control in every time slot, fewer hypoglycemia and reduced glycemic variability. KEY WORDS basal insulins; hospitalized patients; hypoglycemia; glycemic variability.
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Kabakov, Anna, and Andrew Merker. "The Comparative Dosing and Glycemic Control of Intermediate and Long-Acting Insulins in Adult Patients With Type 1 and 2 Diabetes Mellitus." Journal of Pharmacy Technology 38, no. 1 (November 10, 2021): 46–53. http://dx.doi.org/10.1177/87551225211055700.
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Objective: The various basal insulin products possess differences in pharmacokinetics that can significantly impact glycemic control and total daily basal insulin dosing. In addition, there will be instances where transitions between the different long-acting insulins will need to be made. Because every basal insulin product is not interchangeable on a 1:1 unit-to-unit basis, it is important for health care providers to understand the expected dose adjustments necessary to maintain a similar level of glycemic control. Data Sources: A Medline and Web of Science search was conducted in September 2021 using the following keywords and medical subjecting headings: NPH, glargine, detemir, type 1 diabetes mellitus, and type 2 diabetes mellitus. Study Selection and Data Extraction: Included articles were those that followed adult patients with type 1 diabetes mellitus and/or type 2 diabetes mellitus and compared the following types of insulin: “NPH and glargine,” “NPH and detemir,” and “glargine and detemir” for at least 4 weeks, had documented basal insulin (BI) doses, and excluded pregnant patients. Data synthesis: Twenty-five articles were found that include adult type 1 and/or type 2 diabetes mellitus patients. Once daily NPH can be converted unit-to-unit to glargine or detemir. Twice daily NPH converted to glargine or detemir requires an initial 20% reduction in BI dose. An increase in dose of BI is recommended when transitioning from glargine to detemir. Glargine and detemir consistently resulted in improved glycemic control with lower incidence of hypoglycemic events compared with NPH. Conclusions: When transitioning between long-acting insulins, the doses are not always interchangeable on a 1:1 basis. Unit dose adjustments are likely if transitioning between BIs and can influence short-term parameters in the acute care setting and long-term parameters in the outpatient setting.
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Stailey, Matthew, and Susan E. Conway. "Review of the Next Generation of Long-Acting Basal Insulins: Insulin Degludec and Insulin Glargine." Consultant Pharmacist 32, no. 1 (January 1, 2017): 42–46. http://dx.doi.org/10.4140/tcp.n.2017.42.
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Corigliano, Sandro. "Nuevas insulinas basales." Diagnóstico 55, no. 4 (December 11, 2018): 206–10. http://dx.doi.org/10.33734/diagnostico.v55i4.62.
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Hace aún menos de un siglo, los médicos no sabían que causaba la Diabetes y por lotantonobabia tratamiento para esta enfermedad. El paciente promedio de la que hoy conocemos como Diabetes mellitus de tipo 1, no so Havivir más de algunas semanas o meses.
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Pyle, Laura, Bryan C. Bergman, Kristen J. Nadeau, and Melanie Cree-Green. "Modeling changes in glucose and glycerol rates of appearance when true basal rates of appearance cannot be readily determined." American Journal of Physiology-Endocrinology and Metabolism 310, no. 5 (March 1, 2016): E323—E331. http://dx.doi.org/10.1152/ajpendo.00368.2015.
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Advancing diabetes care requires accurate physiological assessments. Hyperinsulinemic clamps with stable isotope tracers can simultaneously measure insulin's ability to suppress lipolysis and hepatic glucose release. Traditionally, these methods require an assessment of basal glucose and glycerol rate of appearance (Ra). Basal Ra is challenging to measure in insulin-dependent diabetes, where exogenous insulin required to maintain normoglycemia can raise peripheral insulin concentrations sufficiently to suppress basal Ra. Thus we identified two alternative statistical approaches to describe changes in glucose and glycerol Ra that are less reliant on basal assessments. Sixteen youths (4 type 1 diabetic, 4 type 2 diabetic, 4 lean controls, and 4 obese nondiabetic) underwent a four-phase (“basal” and 10, 16, and 80 mU·m2·min−1) hyperinsulinemic euglycemic clamp with glucose and glycerol tracers. Glucose and glycerol Ra were calculated per phase. A statistical method, the standard two-stage (STS) algorithm, was applied to the individual log insulin vs. Ra curves to calculate a single predicted Ra value. A population-based mixed-effects model (MEM) compared the group average Ra with log insulin curves and described individual deviations from group means and was used to calculate individual predicted Ra. Both models were applied to the participant data, and predicted Ras at the mean insulin concentration per phase (10 for glycerol, 16 for glucose) were calculated, with good agreement between observed and predicted values. In our data set, the MEM was better able to detect group differences. Both STS and MEM can model lipolysis and endogenous glucose release in insulin-dependent states when basal Ra cannot be accurately measured.
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Buren, J., HX Liu, J. Lauritz, and JW Eriksson. "High glucose and insulin in combination cause insulin receptor substrate-1 and -2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: possible implications for insulin resistance in type 2 diabetes." European Journal of Endocrinology 148, no. 1 (January 1, 2003): 157–67. http://dx.doi.org/10.1530/eje.0.1480157.
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OBJECTIVE: The purpose of this study was to investigate the cellular effects of long-term exposure to high insulin and glucose levels on glucose transport and insulin signalling proteins. DESIGN AND METHODS: Rat adipocytes were cultured for 24 h in different glucose concentrations with 10(4) microU/ml of insulin or without insulin. After washing, (125)I-insulin binding, basal and acutely insulin-stimulated d-[(14)C]glucose uptake, and insulin signalling proteins and glucose transporter 4 (GLUT4) were assessed. RESULTS: High glucose (15 and 25 mmol/l) for 24 h induced a decrease in basal and insulin-stimulated glucose uptake compared with control cells incubated in low glucose (5 or 10 mmol/l). Twenty-four hours of insulin treatment decreased insulin binding capacity by approximately 40%, and shifted the dose-response curve for insulin's acute effect on glucose uptake 2- to 3-fold to the right. Twenty-four hours of insulin treatment reduced basal and insulin-stimulated glucose uptake only in the presence of high glucose (by approximately 30-50%). At high glucose, insulin receptor substrate-1 (IRS-1) expression was downregulated by approximately 20-50%, whereas IRS-2 was strongly upregulated by glucose levels of 10 mmol/l or more (by 100-400%). Insulin treatment amplified the suppression of IRS-1 when combined with high glucose and also IRS-2 expression was almost abolished. Twenty-four hours of treatment with high glucose or insulin, alone or in combination, shifted the dose-response curve for insulin's effect to acutely phosphorylate protein kinase B (PKB) to the right. Fifteen mmol/l glucose increased GLUT4 in cellular membranes (by approximately 140%) compared with 5 mmol/l but this was prevented by a high insulin concentration. CONCLUSIONS: Long-term exposure to high glucose per se decreases IRS-1 but increases IRS-2 content in rat adipocytes and it impairs glucose transport capacity. Treatment with high insulin downregulates insulin binding capacity and, when combined with high glucose, it produces a marked depletion of IRS-1 and -2 content together with an impaired sensitivity to insulin stimulation of PKB activity. These mechanisms may potentially contribute to insulin resistance in type 2 diabetes.
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Nasrallah, Sami N., and L. Raymond Reynolds. "Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?" Clinical Medicine Insights: Endocrinology and Diabetes 5 (January 2012): CMED.S9494. http://dx.doi.org/10.4137/cmed.s9494.
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The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated. 1 , 2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours. 3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual. 4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety. 5
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Jermendy, György, and 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, no. 50 (December 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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Blanco Naranjo, Erick Gerardo, Gary Felipe Chavarría Campos, and Yorlin María Garita Fallas. "Insulinización práctica en la diabetes mellitus tipo 2." Revista Medica Sinergia 6, no. 1 (January 1, 2021): e628. http://dx.doi.org/10.31434/rms.v6i1.628.
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La diabetes mellitus tipo 2 se caracteriza por ser una enfermedad crónica de naturaleza progresiva, con un estado de hiperglicemia y grados variables de deficiencia y resistencia a la insulina. En esta patología la educación y el apoyo para el autocontrol de la diabetes son críticos para prevenir complicaciones agudas y reducir el riesgo de complicaciones a largo plazo. La terapia de insulinización ha demostrado ser un auxilio eficaz para mejorar la calidad de vida de pacientes con diabetes mellitus tipo 2 y evitar complicaciones. Existen dos grandes grupos de insulinas que son las insulinas humanas y los análogos de insulina; la primera, ha demostrado ser una opción efectiva y menos costosa, por esta razón los médicos deben estar familiarizados con su uso. Se pueden utilizar diversos esquemas para la insulinización, el esquema basal es el que ha demostrado mayor reducción de los niveles glicémicos y menor riesgo de hipoglicemia; además, es sencillo lo que facilita la adherencia de los pacientes al tratamiento.
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Papa, G. "New horizons for insulin therapy with a pump: the artificial pancreas." Journal of AMD 24, no. 2 (July 2021): 86. http://dx.doi.org/10.36171/jamd21.24.2.2.
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The monitoring and treatment of type 1 diabetes (T1D) are undergoing profound changes today. Notable steps include the improvement and widespread adoption of glucose sensors which are now extremely reliable and furthermore are used with insulin pumps in an integrated manner. Over the last 2 to 3 years these systems have evolved rapidly with the development and use of algorithms which permit the autonomous regulation of basal insulin. Correct control and administration of basal insulin is often the greatest stumbling block in multiple daily injection therapy as basal insulins cannot replicate the physiological rhythms of basal insulin secretion. Hypoglycemia is another critical point in standard insulin pen therapy as it does not permit dosage modulation in the same way as with an insulin pump. In this article we cover the fundamental steps in this revolution of insulin therapy which promises, in the not too distant future, the ultimate achievement of the artificial pancreas and thus the complete closure of the loop. All those working in diabetes care must be adequately trained and familiar with this technology as it should no longer be considered a niche treatment reserved for carefully selected patients and managed in only a few centers of excellence. In order to choose the best treatment, tailored to each individual patient’s needs, medical staff involved in the treatment of T1D require a thorough knowledge of standalone glucose sensors, insulin pumps and integrated systems with control algorithms.Once the critical issues (costs, psychological aspects, system management difficulties, alarm fatigue, etc.) still related to their use have been resolved, new Hybrid Closed Loop and Advanced Hybrid Closed Loop systems could become the new standard in the treatment of T1D. KEY WORDS type 1 Diabetes; insulin pump; decision-making algorithms; integrated system.
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Andrianova, E. A. "The use of ultra-short acting insulin preparations for insulin pumps." Problems of Endocrinology 58, no. 3 (June 15, 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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Swigert, Tamara J. "Basal Insulin Titration." AADE in Practice 2, no. 2 (February 24, 2014): 34–40. http://dx.doi.org/10.1177/2325160313518042.
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Clore, John N., and Linda Thurby-Hay. "Basal insulin therapy." Current Diabetes Reports 4, no. 5 (September 2004): 342–45. http://dx.doi.org/10.1007/s11892-004-0035-3.
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Kruger, Davida F. "Basal-Prandial Insulin." Nurse Practitioner 32, no. 5 (May 2007): 24–29. http://dx.doi.org/10.1097/01.npr.0000269469.80928.20.
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&NA;. "Basal-Prandial Insulin." Nurse Practitioner 32, no. 5 (May 2007): 30. http://dx.doi.org/10.1097/01.npr.0000269470.88552.d7.
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Simó, Rafael. "Nueva insulina basal de acción ultralenta: insulina degludec." Avances en Diabetología 29, no. 1 (January 2013): 4–11. http://dx.doi.org/10.1016/j.avdiab.2012.11.001.
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Caprio, S., G. Cline, S. Boulware, C. Permanente, G. I. Shulman, R. S. Sherwin, and W. V. Tamborlane. "Effects of puberty and diabetes on metabolism of insulin-sensitive fuels." American Journal of Physiology-Endocrinology and Metabolism 266, no. 6 (June 1, 1994): E885—E891. http://dx.doi.org/10.1152/ajpendo.1994.266.6.e885.
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Insulin's ability to stimulate glucose metabolism is reduced during normal puberty; these changes are exaggerated in adolescents with insulin-dependent diabetes mellitus (IDDM). Because the effects of puberty and IDDM on the other actions of insulin have not been established, we studied leucine kinetics (using [1-13C]leucine) and fat metabolism during euglycemic hyperinsulinemia (20 mU.m2.min-1) for 3 h in eight healthy and nine IDDM (HbA1 14 +/- 2%) adolescents and six healthy young adult controls. IDDM subjects received overnight low-dose insulin infusion to normalize fasting glucose. Basal and steady-state insulin values (approximately 240 pM) during the study were similar in all three groups. Insulin-stimulated glucose metabolism was reduced by 40% in healthy adolescents vs. adults (P < 0.05) and by an additional 40% in poorly controlled IDDM (P < 0.05 vs, normal adolescents). Although basal glucose and lipid oxidation rates (measured by indirect calorimetry) were similar in all three groups, when insulin was infused, glucose oxidation increased and lipid oxidation decreased only in the two nondiabetic groups. Similarly, insulin significantly reduced plasma free fatty acid levels only in the nondiabetics. Basal leucine flux (an index of protein degradation) was similar in healthy controls but was markedly increased in IDDM adolescents. Despite similar increments in plasma insulin during the clamp, leucine flux remained higher in IDDM adolescents than in healthy controls. Basal leucine oxidation rates were also increased in IDDM subjects compared with nondiabetic groups and declined to a lesser extent during insulin infusion. We conclude that insulin resistance of puberty is selective for glucose metabolism, sparing amino acid/protein metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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Nagy, Erzsébet, and Gábor Kovács. "Humán inzulinról glargininzulin-alapú bázis-bolus kezelésre váltott betegek glykaemiás állapotának javulása a váltás után." Orvosi Hetilap 159, no. 29 (July 2018): 1201–7. http://dx.doi.org/10.1556/650.2018.31007.
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Abstract: Introduction: The effectiveness of human and analogue insulins is similar but the latter have more advantageous pharmacokinetic features, leading to an improvement in hypoglycaemia and come closer to achieving the physiologic insulin profile. Aim: To demonstrate that switching from a human basal-bolus insulin treatment to an insulin glargine-based basal-bolus regimen can achieve a better glycaemic control. Method: This 3-month prospective, non-interventional study, including a 12-month retrospective data collection phase, enrolled patients who were switched to the insulin glargine- – 100 U/mL – based basal-bolus treatment at the time of enrolment if they were inadequately controlled and had at least one additional HbA1c result in the 12 months before the switch. Of 1513 patients 1181 had the data that were needed for the efficacy analysis. Results: The mean age of the efficacy population was 58.3 years and 48.1% were male. Their mean HbA1c levels remained unchanged in the year before the switch: it was 8.8 ± 1.4% at 12 months prior to the switch and 8.8 ± 1.2% at the switch, but decreased significantly to 7.7 ± 1.0% (p<0.001) after 3 months. Between the baseline and 3 months, the fasting blood glucose and the postprandial blood glucose improved significantly (from 10.0 ± 3.2 mmol/L to 7.4 ± 1.9 mmol/L, p<0.001 and from 11.1 ± 2.8 mmol/L to 8.8 ± 1.7 mmol/L, p<0.001, respectively). Insulin doses were increased both before and after the switch. Conclusions: Switch to an insulin glargine-based basal-bolus regimen could achieve a significant improvement in the glycaemic control in patients who were inadequately controlled prior to the switch. Orv Hetil. 2018; 159(29): 1201–1207.
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Begum, N. "Phenylarsine oxide inhibits insulin-stimulated protein phosphatase 1 activity and GLUT-4 translocation." American Journal of Physiology-Endocrinology and Metabolism 267, no. 1 (July 1, 1994): E14—E23. http://dx.doi.org/10.1152/ajpendo.1994.267.1.e14.
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Phenylarsine oxide (PAO) has previously been shown to inhibit insulin-stimulated glucose transport without affecting insulin binding and tyrosine kinase activity of insulin receptor (S. C. Frost and M. D. Lane. J. Biol. Chem. 260: 2646-2652, 1985). This study examines the effect of PAO on insulin's ability to activate adipocyte protein phosphatase 1 (PP-1) and dephosphorylate GLUT-4, the insulin-sensitive glucose transporter. In particulate fractions, insulin stimulated PP-1 activity (40% increase over basal with phosphorylase a) in a time- and dose-dependent manner (half-maximal effect of 0.89 nM in 1 min). Insulin did not alter cytosolic PP-1 activity. With GLUT-4 as a substrate, insulin caused more than twofold stimulation of particulate PP-1 activity. Addition of PAO (5 microM) before or after insulin treatment abolished insulin's effect on PP-1 activation. The presence of 2,3-dimercaptopropanol (200 microM) prevented the effect of PAO on PP-1 activation and glucose uptake. In addition, PAO significantly increased GLUT-4 phosphorylation, blocked insulin-stimulated dephosphorylation, and partially diminished insulin-stimulated translocation of GLUT-4. We conclude that PAO may interfere with the components of insulin signal transduction pathways that lead to the activation of PP-1 and this may be responsible for the observed inhibition in insulin action.
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Mikhail, Nasser. "Insulin U-500, the Practical Solution for the treatment of Patients with High Insulin Requirements." Current Diabetes Reviews 17, no. 1 (December 4, 2020): 26–29. http://dx.doi.org/10.2174/1573399816666200408084614.
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Background: Human regular insulin 500 (U-500) is 5 five times more concentrated than the traditional regular human insulin (U-100). Thus, every 1 ml of U-500 contains 500 units of insulin as opposed to 100 units/ml with most types of insulin. Methods: Review of all the relevant clinical studies related to insulin U-500 until February 12, 2020. Results: Insulin U-500 is indicated in patients with type 2 diabetes who require more than 200 units of insulin per day. Insulin U-500 has both prandial and basal actions, and can be injected as monotherapy in a convenient twice-daily regimen. Available data suggest that insulin U-500 is effective, associated with better compliance, and decreased injection pain compared with non-concentrated insulins. Its main limitations are hypoglycemia and weight gain, and the possibility of dosing errors. Conclusions: Overall, insulin U-500 is an effective and safe treatment for patients with type 2 diabetes and insulin resistance. Randomized trials are needed to compare the long-term efficacy and safety of insulin U-500 with other forms of insulin regimens.
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Girón-Ortega, José Antonio, Salvador Ignacio Pérez-Galera, Rocío Ruiz-Hueso, and David León-Jiménez. "Insulinas basales… ¡A jugar!" Revista Española de Casos Clínicos en Medicina Interna 4, s1 (January 2019): 7–10. http://dx.doi.org/10.32818/reccmi.a4s1a4.
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En este caso clínico, se muestra la utilidad de los sensores continuos de glucosa, con el fin de descubrir pacientes que por hemoglobina glicosilada están aparentemente bien tratados cuando la realidad es otra completamente diferente: mucha variabilidad, hipoglucemias inadvertidas. El uso de las nuevas insulinas lentas permite controlar mejor la variabilidad de muchos pacientes, al tiempo que disminuye el riesgo de hipoglucemias.
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Kalra, Sanjay, Manash Baruah, AmbikaGopalakrishnan Unnikrishnan, and Bharti Kalra. "Degludec insulin: A novel basal insulin." Indian Journal of Endocrinology and Metabolism 15, no. 5 (2011): 12. http://dx.doi.org/10.4103/2230-8210.83056.
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Russell-Jones, David L. "Insulin Detemir and Basal Insulin Therapy." Endocrinology and Metabolism Clinics of North America 36 (August 2007): 7–13. http://dx.doi.org/10.1016/s0889-8529(07)80003-x.
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