[Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin

Howey, D. C.; Bowsher, R. R.; Brunelle, Rocco L.; Woodworth, J. R.

doi:10.2337/diabetes.43.3.396

Cited by 248 publications

(213 citation statements)

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“…Thus, in a euglycemic clamp study in normal subjects, the peak serum insulin concentration was significantly higher (116 vs. 51 mU/mL [698 vs. 308 pmol/L]) and earlier (42 vs. 101 minutes) after the subcutaneous administration of insulin lispro than after regular insulin. 22 The rates of glucose infusion needed to maintain euglycemia followed a similar pattern. 22 Likewise, insulin glulisine reached twice the peak insulin concentration and had a time to peak concentration approximately twice as fast as that of regular human insulin.…”

Section: Rapid-acting Analogsmentioning

confidence: 74%

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

Hartman

2008

Clinical Medicine & Research

116

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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: 74%

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

Hartman

2008

Clinical Medicine & Research

116

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“…Preprandial regular insulin, which has a more delayed onset, lower peak concentration, and longer duration of action compared with ultra-short-acting insulin (15,16), may better match the absorption profile of low-glycemic index foods. However, postprandial ultra-short-acting insulin has been demonstrated to produce higher PPGEs compared with preprandial administration (17,18), and this may be another alternative approach to optimizing insulin therapy for a lowglycemic index meal, as suggested by the British Dietetics Association in its 2005 consensus statement (19).…”

mentioning

confidence: 99%

Influence of and Optimal Insulin Therapy for a Low–Glycemic Index Meal in Children With Type 1 Diabetes Receiving Intensive Insulin Therapy

et al. 2008

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OBJECTIVE -The purpose of this study was to quantify the effects of glycemic index on postprandial glucose excursion (PPGE) in children with type 1 diabetes receiving multiple daily injections and to determine optimal insulin therapy for a low-glycemic index meal.RESEARCH DESIGN AND METHODS -Twenty subjects consumed test breakfasts with equal macronutrient contents on 4 consecutive days; high-and low-glycemic index meals (glycemic index 84 vs. 48) were consumed with preprandial ultra-short-acting insulin, and the low-glycemic index meal was also consumed with preprandial regular insulin and postprandial ultra-short-acting insulin. Each child's insulin dose was standardized. Continuous glucose monitoring was used.RESULTS -The PPGE was significantly lower for the low-glycemic index meal compared with the high-glycemic index meal at 30 -180 min (P Ͻ 0.02) when preprandial ultra-shortacting insulin was administered. The maximum difference occurred at 60 min (4.2 mmol/l, P Ͻ 0.0001). Regular insulin produced a 1.1 mmol/l higher PPGE at 30 min compared with ultrashort-acting insulin (P ϭ 0.015) when the low-glycemic index meal was consumed. Postprandial ultra-short-acting insulin produced a higher PPGE at 30 and 60 min compared with preprandial administration when the low-glycemic index meal was consumed. The maximum difference was 2.5 mmol/l at 60 min (P Ͻ 0.0001).CONCLUSIONS -Low-glycemic index meals produce a lower PPGE than high-glycemic index meals. Preprandial ultra-short-acting insulin is the optimal therapy for a low-glycemic index meal.

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“…The rapid absorption of these insulin analogues from the injection site is associated with a faster peak insulin concentration and a shorter duration of action than that achievable with regular human insulin [22][23][24]. This represents a more accurate simulation of physiological insulin release in response to a meal and results in lower postprandial glucose concentrations.…”

Section: Insulin Analoguesmentioning

confidence: 99%

“…The first, in 1996, was insulin lispro (Humalog ® , Eli Lilly and Co, IN, USA) [22]. A second insulin analogue, insulin aspart (NovoRapid ® , Novo Nordisk, Denmark), was introduced in 1999 [23].…”

Section: Insulin Analoguesmentioning

confidence: 99%

Insulin Aspart in Diabetic Pregnancy: State of the Art

Mathiesen

2008

Womens Health (Lond Engl)

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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.Pregnancy outcome among women with Type 1 or Type 2 diabetes is still significantly poorer than in the background population [1]. This review will focus on pregnant women with Type 1 diabetes. Optimal glycemic control is crucial in order to reduce the risk of congenital malformations, stillbirth, macrosomia, preeclampsia and preterm delivery [2][3][4][5]. The results of population-based cohort studies conducted in Europe, mainly using human insulin, demonstrate unequivocally that women with Type 1 diabetes have an increased risk of late fetal loss, with an approximate four-to five-fold increase in perinatal death and a four-to sixfold increase in stillbirth relative to the national background population [1][2][3][4][5][6].Reports have attributed the increased risk of congenital abnormalities in diabetic mothers to poor metabolic control during the critical period of organogenesis in the first trimester of pregnancy [7,8]. Population-based cohort studies have reported incidences of congenital malformations ranging from two-to ten-times higher than the background population in the UK [6]. The risk of major congenital abnormalities among offspring of women with diabetes is predominantly accounted for by congenital heart disease, bone malformations and neural tube anomalies [1].The rate of premature deliveries (defined as delivery before 37 weeks' gestation) are four-to five-fold higher among pregnant women with diabetes compared with the general maternity population [7]. The rate of preterm delivery in the UK diabetic population was 36%, compared with 7% for the general maternity population. Preterm infants of women with pregestational diabetes are at significantly greater risk of complications, including hyperbilirubinemia, respiratory disorders, hypertrophic cardiomyopathy and asphyxia, than those born to nondiabetic mothers [7].Macrosomia is probably mediated by fetal hyperinsulinemia in response to maternal hyperglycemia. Recent studies report that rates of macrosomia (>90th percentile weight for gestational ag...

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[Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin

Cited by 248 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

Influence of and Optimal Insulin Therapy for a Low–Glycemic Index Meal in Children With Type 1 Diabetes Receiving Intensive Insulin Therapy

Insulin Aspart in Diabetic Pregnancy: State of the Art

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