Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM

Torlone, Elisabetta; Fanelli, Carmine G.; Rambotti, A. M.; Kassi, Georgia; Modarelli, F.; Vincenzo, Angelo Di; Epifano, L.; Ciofetta, M.; Pampanelli, S.; Brunetti, P; Bolli, Geremia B.

doi:10.1007/bf00417697

Cited by 117 publications

(119 citation statements)

References 23 publications

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“…The dissociation of hexamers is facilitated in short-acting insulin analogues (SAI analogues), and these achieve peak plasma concentrations about twice as high and within approximately half the time compared with regular insulin [3,4]. Despite the theoretical superiority of SAI analogues over regular insulin, the efficacy of SAI analogues in the treatment of diabetic patients is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of short-acting insulin analogues in adult patients with type 1 diabetes: continuous subcutaneous insulin infusion versus injection therapy

Siebenhofer¹,

Plank²,

Berghold

et al. 2004

Diabetologia

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Aims/hypothesis. This study aimed to compare the effect of treatment with short-acting insulin (SAI) analogues versus structurally unchanged short-acting insulin (regular insulin) on glycaemic control and on the risk of hypoglycaemic episodes in type 1 diabetic patients using different insulin treatment strategies. Methods. We performed a meta-analysis of 27 randomised controlled trials that compared the effect of SAI analogues with regular insulin in patients with type 1 diabetes mellitus. The treatments were administered either via continuous subcutaneous insulin infusion (CSII) or by conventional intensified insulin therapy (IIT) with short-acting insulin injections before meals and basal insulin administered once or twice daily in most cases. Results. HbA 1 c levels were reported for 20 studies. For studies using CSII, the weighted mean difference between values obtained using SAI analogues and regular insulin was −0.19% (95% CI: −0.27 to − 0.12), whereas the corresponding value for injection studies was −0.08% (95% CI: −0.15 to −0.02). For the analysis of overall hypoglycaemia, we used the results from nine studies that reported the mean frequency of hypoglycaemic episodes per patient per month. For studies using CSII, the standardised mean difference between SAI analogues and regular insulin was −0.07 (95% CI: −0.43 to 0.28), whereas for IIT studies the corresponding value was −0.04 (95% CI: −0.24 to 0.16). Conclusions/interpretation. Taking into consideration the low quality of the trials included, we can conclude that use of a short-acting insulin analogue in CSII therapy provides a small, but statistically significant improvement in glycaemic control compared with regular insulin. An even smaller effect was obtained with the use of ITT. The rate of overall hypoglycaemic episodes was not significantly reduced with short-acting insulin analogues in either injection regimen.

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Section: Introductionmentioning

confidence: 99%

Meta-analysis of short-acting insulin analogues in adult patients with type 1 diabetes: continuous subcutaneous insulin infusion versus injection therapy

Siebenhofer¹,

Plank²,

Berghold

et al. 2004

Diabetologia

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“…However, in the daily life of patients with Type I diabetes, hypoglycaemia could occur in the postprandial condition, particularly when the insulin dose is inappropriately high for the carbohydrate content of the meal. After a s.c. injection of rapid-acting insulin analogue, hypoglycaemia is expected to occur earlier than with human regular insulin [9,10]. In addition, in the postprandial phase, people generally either sit or stand.…”

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confidence: 99%

Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state

et al. 2003

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Aims/hypothesis. The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position. Methods. We studied 11 subjects with Type I (insulindependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1±0.003 mmol· min -1 ·l -1 (fast fall), on the other at the rate of 0.03±0.001 mmol·min -1 ·l -1 (slow fall). Subjects underwent a control euglycaemic clamp study as well. Results. In response to fast-fall as compared to slowfall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: TrailMaking B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8±0.5 vs 3.5±0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5±1.0 vs 5.2±0.4 pmol·min -1 ·100 ml -1 , p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state. Conclusion/interpretation. In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia. [Diabetologia (2003) 46:53-64] Keywords Type I diabetes mellitus, postprandial hypoglycaemia, glucose counterregulation, cognitive dysfunction, forearm noradrenaline spillover. acting insulin analogue as compared to human regular insulin, the technique of s.c. injection, insulin sensitivity and meal size and composition, are usually considered the most important determinants of the rate of decreasing postprandial blood glucose concentrations. After s.c. injection of rapid-acting insulin analogues [1], the rate of decreasing blood glucose is greater than after injecting human regular insulin [2,3]. Therefore, it is expected that when hypoglycaemia is induced by mealtime administration of rapid-acting insulin analogue, the rate of decreasing blood glucose is greater than after injecting human regular insulin. In theory, different rates of decreasing blood glucose in the postprandial condition might result in different reWhen patients with Type I (insulin-dependent) diabetes mellitus experience hypoglycaemia after a subcutaneous (s.c.) injection of rapid-acting insulin at mealtime, blood glucose decreases to below normal concentrations at rates which can differ on different occasions. Among several factors, the injection of a rapid-

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“…Esta insulina tem menor tendência para auto-agregação no local de aplicação subcutânea, é absorvida mais rapidamente que a insulina humana regular, e mimetiza o perfil fisiológico da insulina em resposta a uma refeição (6). Como resultado, ela tem um início de ação rápido (15 minutos), atinge um pico de ação mais precocemente (1 hora) e possui uma duração de ação mais curta (4 horas) (6)(7)(8)(9)(10)(11)(12). Estudos clínicos demonstraram que esta insulina monomérica tem efeitos benéficos, como a redução da incidência de episódios hipoglicêmicos (12-16) e um melhor controle glicêmico pós-prandial (17)(18)(19)(20)(21)(22)(23)(24)(25).…”

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Menor incidência de hipoglicemia noturna com o uso de insulina lispro comparada à insulina humana regular no tratamento de pacientes com diabetes do tipo 1

Wajchenberg

Chacra

Forti

et al. 2000

Arq Bras Endocrinol Metab

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Recebido em 01/06/99 Revisado em 26/08/99Aceito em 20/12/99 RESUMOInsulina lispro é um análogo da insulina humana de ação e duração rá-pida, que mimeíiza o perfil fisiológico da insulina após uma refeição. Avaliamos a segurança e eficácia da insulina lispro em comparação com a insulina humana regular em um estudo multicêntrico, randomizado e cruzado em 27 diabéticos tipo 1 em uso de insulina humana NPH e regular (idade mediana = 16 anos). Após uso de insulina lispro ou regular por 2 meses, fez-se a transferência para a outra insulina por mais 2 meses mantendo-se a insulina NPH basal. Não houve diferença em relação à excursão prandial da glicemia da hemoglobina glicosilada A1C, comparando-se os 2 grupos (lispro e regular). O decréscimo percentual relativo da glicemia foi significantemente maior com insulina lispro no período do almoço, na primeira fase do estudo (p<0,02). O número total de episó-dios hipoglicêmicos não foi diferente, comparando os 2 grupos. Houve, porém, uma redução significante na incidência de hipoglicemia noturna e na madrugada com o uso inicial de lispro (p<0,05). Com o uso inicial de insulina regular, houve incremento na incidência de hipoglicemia noturna (p=0,038), com redução posterior na incidência da hipoglicemia com insulina lispro (p=0,04). Ao final do estudo, 68% dos pacientes referiram preferência e maior comodidade com insulina lispro em relação à insulina regular. A insulina lispro se mostrou uma opção segura e eficaz, com menor incidência de hipoglicemia noturna em diabéticos tipo 1. Uma otimização do regime de insulina basal é necessária para melhora do controle glicêmico, quando em uso de uma insulina de ação rápida. ABSTRACTInsulin lispro is a human insulin analog of rapid onset of action and duration, which mimics the physiological insulin profile after a meal. We have evaluated the safety and efficacy of lispro insulin in comparison with human regular insulin in a crossover, multicenter, randomized trial in 25 type 1 diabetic patients in use of human NPH and regular insulin (median age = 16 years). After administration of lispro or regular insulin for 2 months, the patients were transferred for the other insulin for two more months, maintaining the basal NPH insulin regimen. There was no difference in the postprandial glucose excursion and glycated hemoglobin A1c comparing the 2 groups (lispro and regular). The relative percentage decrease in glycemia was significantly greater with lispro insulin after lunch, in the first phase of the study (p<0.02). The total number of hypo--glycemic episodes was not different comparing both groups. However, there was a significant difference in the nocturnal hypoglycemia incidence with initial administration of lispro (p<0.05). With initial administration of regular insulin, there was an increase in the incidence of nocturnal hypoglycemia (p=0.038), with a subsequent reduction of hypoglycemia with insulin lispro (p=0.04). In the end of the study, 68% of the patients referred preference and better feeling with lispro, compared to regular in...

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Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM

Cited by 117 publications

References 23 publications

Meta-analysis of short-acting insulin analogues in adult patients with type 1 diabetes: continuous subcutaneous insulin infusion versus injection therapy

Meta-analysis of short-acting insulin analogues in adult patients with type 1 diabetes: continuous subcutaneous insulin infusion versus injection therapy

Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state

Menor incidência de hipoglicemia noturna com o uso de insulina lispro comparada à insulina humana regular no tratamento de pacientes com diabetes do tipo 1

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