Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.

Mudaliar, Sunder; Lindberg, Fedon A.; Joyce, M.; Beerdsen, P.; Strange, Poul; Lin, Alex C.; Henry, Robert R.

doi:10.2337/diacare.22.9.1501

Cited by 243 publications

(170 citation statements)

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“…One study, however, showed that abdominal injection of aspart was associated with a significantly shorter duration of effect compared to other sites. 11 These studies also demonstrated a more rapid taper of metabolic activity of the insulin analogs relative to regular insulin. Finally, insulin aspart was found to have a lower range of pharmacokinetic and pharmacodynamic variability than human insulin (10% to 20%).…”

Section: Rapid-acting Analogsmentioning

confidence: 81%

“…However, the molecular changes do not alter the biological properties of the analogs in terms of binding to the insulin receptor, and the rapid-acting insulin analogs all possess the same glucose-lowering effects as human insulin. [10][11][12] Long-Acting Basal Insulin Analogs There are currently two long-acting basal insulin analog preparations available for commercial use: insulin glargine and insulin detemir (table 1). Both analogs have been designed to provide consistent, relatively flat, and protracted basal insulin levels, features which result from their specific molecular modifications relative to the human insulin molecule.…”

Section: Rapid-acting Insulin Analogsmentioning

confidence: 99%

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Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

Hartman

2008

Clinical Medicine & Research

113

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Despi te 85 years of research since Banting and Best's isolation of insulin-containing extracts, 1 diabetes still remains one of the most significant causes of morbidity and mortality in the world, and its global impact is likely to accelerate over the coming decades. 2,3 Much of the medical and economic consequences of diabetes are attributable to its associated microvascular and macrovascular complications. [4][5][6] Two classic large-scale clinical studies, the Diabetes Control and Complications Trial (DCCT) 6 and the UK Prospective Diabetes Study (UKPDS), 7 demonstrated that intensive blood-glucose control policies can decrease the frequency of complications, arguing that physicians and patients should strive to mimic, as closely as possible, the serum levels of insulin produced by a healthy person. Secretion of insulin by the pancreas, however, is under complex regulation that depends on the intake of nutrients, other gastrointestinal peptides (e.g., incretins), and overall metabolic levels (i.e., exercise versus rest). 8 These physiological variables, which pose real challenges to the accurate metabolic replacement of insulin, are further complicated by the fact that diabetes requires self-management and therefore depends on the psychology, motivation, and understanding of the patient. A growing body of medical research has demonstrated that intensive control of serum glucose levels can minimize the development of diabetes-related complications. Success with insulin management ultimately depends on how closely a given regimen can mimic normal physiologic insulin release patterns.The new insulin analogs, including the rapid-acting analogs (aspart, lispro, glulisine), the long-acting basal analogs (glargine, detemir), and the premixed insulin analog formulations (75% neutral protamine lispro, 25% lispro; 50% neutral protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been formulated to allow for a closer replication of a normal insulin profile.The rapid-acting analogs can be administered at mealtimes and produce a rapid and short-lived insulin spike to address postprandial glucose elevations, while the long-acting analogs come close to the ideal of a smooth, relatively flat, 24-hour basal insulin supply, with less variability in action compared to NPH insulin. Despite these clear pharmacologic advantages, measurable clinical benefits in a complex disease such as diabetes can be hard to measure.To date, reviews of insulin analog studies have not found a dramatic overall improvement in glycosylated hemoglobin (HbA1c) outcomes compared to traditional human insulins, although all-analog basal-bolus regimens were associated with significantly lower HbA1c than all-human-insulin basal bolus regimens in some studies. Beyond HbA1c comparisons, however, insulin analogs have been shown in many instances to be associated with lower risks of hypoglycemia, lower levels of postprandial glucose excursions, better patient adherence, greater quality of life, and higher satisfaction with treatment.The long-act...

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Section: Rapid-acting Analogsmentioning

confidence: 81%

Section: Rapid-acting Insulin Analogsmentioning

confidence: 99%

Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

Hartman

2008

Clinical Medicine & Research

113

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“…One milestone towards optimised glycaemic control are rapid and long-acting insulin analogues that more closely mimic the physiological insulin response to a meal following injection [1,2] and achieve sufficient basal day-long glycaemic control [3]. The characteristics are based on the fact that modification of the amino acid sequence of the insulin molecule results in distinguished hexamer formation and therefore altered absorption kinetics.…”

Section: Introductionmentioning

confidence: 99%

Tissue selectivity of insulin detemir action in vivo

et al. 2006

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Aims/hypothesis: Recombinant DNA technology is a useful tool that can be used to create insulin analogues with modified absorption kinetics to improve glycaemic control in patients with type 1 and type 2 diabetes. Among conventional insulin analogues, which are usually created by amino acid exchange, insulin detemir is the first analogue to be acylated with a fatty acid to enable reversible albumin binding. In this study we determined activation of the insulin receptor (IR)-signalling cascade by insulin detemir at the level of IR and IR substrate (Irs) phosphorylation, as well as downstream signalling elements such as phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo. Methods: C57Bl/6 mice were injected i.v. with either insulin detemir or human insulin and Western blot analysis was performed on liver, muscle, hypothalamic and cerebrocortical tissues. Moreover, cerebrocortical activity was detected by EEG in awake mice and cerebral insulin concentrations were measured following human insulin and insulin detemir injection. Results: The time course and extent of IR phosphorylation in peripheral tissues were similar following insulin detemir treatment compared with human insulin, but insulin signalling in hypothalamic and cerebrocortical tissue determined by tyrosine-phosphorylation of the IR and Irs2 proteins occurred faster and was enhanced due to a higher insulin detemir concentration in the brain. Moreover, epidural EEG in mice displayed increased cortical activity using insulin detemir. Conclusions/interpretation: Taken together, these data suggest that insulin detemir has a tissue-selective action, with a relative preference for brain compared with peripheral tissues.

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“…The Henry activity curve for insulin suggests that the higher the concentration of pre-meal insulin, the greater its effect on reducing non-meal blood glucose, and the stronger the 'tail effect' on pre-meal glucose levels. 22 A lower pre-meal dose of insulin can reduce the additive effect of the basal dose and thereby avoid modulating the basal dose. Suzuki et al 23 showed that increasing the basal insulin dose might be a useful way to control FBG and HbA 1c in patients with type 2 diabetes mellitus whose basal insulin was switched from NPH insulin to insulin glargine.…”

Section: Discussionmentioning

confidence: 99%

Comparison of continuous subcutaneous insulin infusion and multiple daily insulin injections in Chinese patients with type 2 diabetes mellitus

et al. 2014

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Objective: To investigate prospectively the insulin dose requirements of Chinese patients with type 2 diabetes mellitus treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) therapy during a 2-week therapeutic intervention. Methods: Patients with type 2 diabetes mellitus were randomly assigned to MDI or CSII therapy. The effects of the two treatment methods were determined based on blood glucose parameters, total daily insulin dose and rates of hypoglycaemia. Results: A total of 609 patients were enrolled in the study. Glycaemic goals were achieved after a mean AE SD of 6.90 AE 2.10 and 5.44 AE 2.22 days' treatment in the MDI and CSII groups, respectively. Once stabilized, the mean AE SD total daily insulin doses were 37.12 AE 10.19 IU and 32.58 AE 8.78 IU for the MDI and CSII groups, respectively. Once stabilized, the mean AE SD total basal and bolus doses were 19.46 AE 7.95 IU/day and 17.66 AE 3.53 IU/day for the MDI group, and 22.79 AE 7.55 IU/ day and 9.81 AE 2.64 IU/day for the CSII group, respectively. There were significant differences in the total, basal and bolus insulin doses between the two groups. Conclusion: CSII therapy may be considered as an effective method to achieve good glycaemic control in Chinese patients with type 2 diabetes mellitus.

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Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.

Cited by 243 publications

References 0 publications

Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

Tissue selectivity of insulin detemir action in vivo

Comparison of continuous subcutaneous insulin infusion and multiple daily insulin injections in Chinese patients with type 2 diabetes mellitus

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