Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation Alone

Sa, J. R.; Alvarenga, Marcelo Alves; Rangel, Érika Bevilaqua; Melaragno, Cláudio S.; Gonzalez, A.M.; Linhares, Marcelo Moura; Salzedas, Alcides; Carmona, Adriana K.; Tonetto-Fernandes, Vânia F.; Gabbay, Merav; Medina-Pestana, J.O.; Dib, Sérgio Atala

doi:10.1111/j.1600-6143.2009.02881.x

Cited by 7 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most likely, these factors play a role in failure of engraftment and/or requirement of a larger mass to effectively control blood glucose. Although studies support these theories, pancreas transplant does not seem to be affected by the same limiting factors and one organ is enough in fully reestablishing glucose homeostasis in diabetic patients (49,54). When islet auto-transplantation is performed in patients undergoing a pancreatectomy, the number of IEq/Kg seems to be lower when compared to allo-transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Islet transplantation outcomes have improved over time with better success rates at one year post-transplant (3,50,51). Pancreas transplantation has been proven successful; and it is now confirmed that one pancreas is sufficient to treat diabetes regardless of insulin resistance, duration of diabetes, and other pre-existing conditions (49,54). On the contrary, most of the time, islets from at least two human pancreata are needed to reverse diabetes in a type-1 patient (6,9,50) evidencing that some major limitations to this procedure and its clinical applicability still exist.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome

et al. 2015

View full text Add to dashboard Cite

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation from 30 to 60% of the islets is lost. In our study, we have investigated: 1) the role of size as a factor affecting islet engraftment and, 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150–300 µm; small, ρ50 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEq), suboptimal (400 IEq), and marginal mass (200 IEq). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 post-transplantation. When the superiority of smaller islets was observed, strategies of over-digestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment as compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet sizes increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly over-digested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed reducing islet size with slight over-digestion and it can be safely adopted to improve clinical outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Outra possibilidade seria o aumento da degradação da insulina no tecido subcutâneo (2) pela ação de duas principais enzimas: insulinase e proteína dissulfide isomerase (3). No entanto, sua fisiopatologia permanece desconhecida e por isso inúmeros tratamentos propostos até o momento mostram-se ineficazes (4).…”

Section: Discussionunclassified

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

Pinheiro

Tácito

Pires

2011

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

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)

show abstract

“…IABs may result in insulin resistance and therefore cause hyperglycemia [105]. In a case study of SC insulin resistance in 7-yr old boy with type 1 DM, it did not prevent sufficient absorption of insulin from Exubera without deteriorating the patient pulmonary function [106].…”

Section: Immunogenicitymentioning

confidence: 99%

Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera

Al-Tabakha

2015

Journal of Controlled Release

View full text Add to dashboard Cite

Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation Alone

Cited by 7 publications

References 16 publications

Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome

Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome

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

Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera

Contact Info

Product

Resources

About