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

Abstract

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.

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

“…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.…”

“…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.…”

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

“…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).…”

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

“…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].…”