Resistance Against Subcutaneous Insulin Successfully Managed With Aprotinin

Müller, W. A.; Taillens, C; Léreret, Serge; Berger, Michael; Philippe, Jacques; Halban, PhilippeA.; Offord, Robin E.

doi:10.1016/s0140-6736(80)91698-0

Cited by 22 publications

(3 citation statements)

References 7 publications

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“…(4,12). Alguns pacientes foram submetidos ao tratamento com inibidores de protease com respostas satisfatórias (13)(14)(15). Entretanto, constituem soluções apenas temporárias, levando-se em consideração sua associação a recorrentes infecções de corrente sanguínea e respostas progressivamente reduzidas do controle glicêmico (4).…”

Section: Discussionunclassified

Extrema resistência à insulina subcutânea e intramuscular em diabetes melito tipo 1

Pinheiro

Tácito

Pires

2011

Arq Bras Endocrinol Metab

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SUMÁRIOResistência insulínica consiste em reduzida resposta celular a esse hormônio e, portanto, disfunção do transporte de glicose para o meio intracelular. Esse fenômeno associa-se a fatores genéticos e principalmente comportamentais relacionados a obesidade e comorbidades a ela associadas como diabetes melito tipo 2, hipertensão arterial e dislipidemia. Entretanto, fatores clínicos de resistência insulínica também estão presentes em diabéticos tipo 1 não obesos na conhecida síndrome de extrema resistência à insulina subcutânea e intramuscular (DRIASM). Condição rara que consiste em resistência à ação da insulina no tecido subcutâneo e muscular e sensibilidade normal, ou próxima do normal, quando administrada via intravenosa. Tratamentos propostos até o momento mostram-se pouco efetivos e se relacionam a complicações e falhas frequentes. Descrevemos dois casos de pacientes femininas de 45 e 46 anos com DRIASM que se diferenciam dos demais já descritos por apresentar diagnóstico de diabetes melito tipo 1 tardio, hiperglicemia constante associada a complicações catabólicas, microvasculares (retinopatia) e neuropáticas sem, no entanto, nenhum episódio de cetoacidose diabética. Os tratamentos propostos variaram desde aplicação de insulina intramuscular e intravenosa até listagem para possível realização de transplante de pâncreas como tentativa de tratamento definitivo. SUMMARYInsulin resistance signs reduced cellular response to this hormone and dysfunction of glucose transport to intracellular compartment. This phenomenon is associated to genetic factors and principally behavior factors correlating to obesity and its comorbidities, as type 2 diabetes mellitus, hypertension and dyslipidemia. However clinical factors of insulin resistance are still present at not obese type 1 diabetes in a known syndrome called type 1 diabetes mellitus with resistance to insulin administered subcutaneously and intramuscularly (DRIASM). This is a rare condition that consists into insulin resistance at subcutaneously and intramuscularly use and normal or near to normal sensitivity at intravenously way. Treatments until now proposed are ineffective and are related to frequent fails and complications. We report here two cases of DRIASM in 45 and 46 female patients that are different from others yet related because they have late diabetes type 1, sustained hyperglycemia associated to catabolic, microangiopathy and neuropathic complications without any ketoacidosis episode. The treatment vary from alternative ways for insulin infusion to inscription to a possible performance of pancreas transplantation like a experiment of definitive treatment. This report was approved by Research Ethic Committee from São José do Rio Preto medical school. Arq Bras Endocrinol Metab. 2011;55(3)

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Section: Discussionunclassified

Extrema resistência à insulina subcutânea e intramuscular em diabetes melito tipo 1

Pinheiro

Tácito

Pires

2011

Arq Bras Endocrinol Metab

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“…Subcutaneous tissue biopsies from brittle diabetic patients whose subcutaneous insulin dose was significantly greater than in stable diabetic patients, showed no greater insulin-degrading activity in vitro than subcutaneous tissue from stable diabetic patients and from normal subjects [9]. Although mixtures of aprotinin and insulin are reported to improve metabolic control and reduce insulin requirements in some diabetic patients who are resistant to high doses of insulin administered subcutaneously [4,5], it is ineffective in other such patients [7,8] as was the case for two of the brittle diabetic patients in this study. In one patient with persistent hyperglycaemia and ketonaemia despite several thousand units of insulin administered subcutaneously per day, aprotinin was ineffective both subcutaneously and intravenously, and also caused anaphylaxis [6].…”

Section: Discussionmentioning

confidence: 99%

“…Brittle diabetic patients have an unpredictable response to subcutaneous insulin with wide swings in metabolic control and often show variable resistance to subcutaneous insulin [3]. Significant improvement in glycaemic control by intravenous [4,5] or intramuscular [3] insulin delivery in these patients suggests that they may have a barrier to the absorption of subcutaneous insulin. This barrier has been attributed to subcutaneous insulin degradation following the observation that aprotinin lowers glycaemic levels and insulin requirements in some but not all brittle diabetic patients [5][6][7][8].…”

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confidence: 99%

Subcutaneous aprotinin causes local hyperaemia

et al. 1983

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Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.

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High protection of animals lethally infected with influenza virus by aprotinin‐rimantadine combination

Жирнов

1987

Journal of Medical Virology

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The successful therapeutic synergism of aprotinin and rimantadine, which are known to attack different viral targets, was demonstrated in influenza-virus-infected animals. Combined treatment with these drugs of mice infected with a highly lethal dose of mouse-adapted influenza virus prevented the development of fatal haemorrhagic pneumonia and protected about 75% of animals; whereas the separate administration of aprotinin and rimantadine induced 35% and 15% protection, respectively.

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Resistance Against Subcutaneous Insulin Successfully Managed With Aprotinin

Cited by 22 publications

References 7 publications

Extrema resistência à insulina subcutânea e intramuscular em diabetes melito tipo 1

Extrema resistência à insulina subcutânea e intramuscular em diabetes melito tipo 1

Subcutaneous aprotinin causes local hyperaemia

High protection of animals lethally infected with influenza virus by aprotinin‐rimantadine combination

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