title: Subcutaneous insulin resistance successfully circumvented on long term by peritoneal insulin delivery from an implantable pump in four diabetic patients.
abstract: Extreme subcutaneous insulin resistance is a rare syndrome characterized by a severe resistance to subcutaneous (S/C) insulin together with persistence of normal or near normal intravenous (IV) insulin sensitivity. Its pathophysiology is unknown, although increased insulin degrading activity has been reported in the S/C adipose tissue fraction in some cases. Until now, proposed treatments have been disappointing. We report 4 cases who were successfully treated by intraperitoneal (IP) route.
  
  
  METHODS
  The diagnosis of subcutaneous insulin resistance was based upon following combined conditions: resistance to hypoglycaemic action of subcutaneous insulin but normal or near normal sensitivity to IV or IP insulin.
  
  
  RESULTS
  4 patients among those followed by EVADIAC group met these criteria: 3 with type 1 diabetes (C peptide=0), the last one with unexplained non insulin-deficient diabetes (no anti-GAD antibodies, C peptide=5 ng/ml). All of them had been treated with subcutaneous insulin therapy without success despite huge doses (up to 4000 IU/day in two patients). The 3 type 1 diabetic patients presented with a history of repeated ketoacidosis episodes. A treatment of insulin mixed with aprotinin had been proposed to 2 patients without success. The IV insulin sensitivity was proved to be normal in two patients by euglycaemic clamp data. A skin biopsy was performed in 1 patient. An accumulation of insulin in the derma was revealed with no increase of degradation products of insulin. In these 4 patients, a dramatic improvement of diabetes control was obtained by IP insulin delivery from an implantable pump (HbA1c decrease by at least 3%).
  
  
  CONCLUSIONS
  Although pathophysiology of the subcutaneous insulin resistance syndrome remains unexplained, our data show that intra-peritoneal insulin therapy from an implantable pump allows diabetes control in patients affected by this uncommon but severely disabling condition.
authors.affiliation: Service de diabétologie et endocrinologie, Hôpital Sud-Francilien, Corbeil-Essonnes, France. jeanpierre.riveline@ch-sud-francilien.fr
authors.forename: J P
authors.initials: JP
authors.lastname: Riveline
authors.forename: M C
authors.initials: MC
authors.lastname: Vantyghem
authors.forename: C
authors.initials: C
authors.lastname: Fermon
authors.forename: C
authors.initials: C
authors.lastname: Brunet
authors.forename: J F
authors.initials: JF
authors.lastname: Gautier
authors.forename: E
authors.initials: E
authors.lastname: Renard
authors.forename: G
authors.initials: G
authors.lastname: Charpentier
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin