title: Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation: preliminary results.
abstract: OBJECTIVE
  Pancreatic islet transplantation (PIT) represents a potential curative treatment for patients with type 1 diabetes, but only 10-15% of patients remain insulin independent 5 years post-transplant. It is not known whether intrinsic insulin resistance exacerbated by immunosuppression plays a pivotal role in low graft survival. The study objective was to understand the changes in insulin resistance, glucose effectiveness (S(g)) and free fatty acid dynamics (FFAd) before and after PIT.
  
  
  METHODS
  Insulin sensitivity index (S(i)), S(g) and FFAd were measured before and after PIT in 10 lean patients, 8 of whom reached insulin independence. Modified Bergman minimal model of frequently sampled intravenous glucose tolerance tests were performed pretransplant and at 12 months post-transplant. Nine non-diabetic control (NDC) subjects matched by age, gender and BMI were used.
  
  
  RESULTS
  Pretransplant S(i) and S(g) were 3.5 ± 0.8 × 10(-5)/min/(pmol/l) and 0.74 ± 0.24 × 10(-2)/min, respectively. S(i) was significantly lower than matched NDCs [10.8 ± 0.6 × 10(-5)/min/(pmol/l), p < 0.004]; S(g) did not reach statistical significance (1.27 ± 0.22 × 10(-2)/min, p = 0.25). Compared to pretransplant values, mean post-transplant S(i) and S(g) were 9.6 ± 1.3 × 10(-5)/min/(pmol/l)and 1.28 ± 0.22 ×10(-2)/min, respectively, indicating significant improvement for S(i) but not S(g) (p = 0.008 and p = 0.06). Twelve-month post-PIT compared to NDC values were not significantly different (p = 0.58 and 0.97, respectively). In addition, fractional disposal rate for FFA which directly depends on the endogenous insulin release (10-20 min) nearly normalized after PIT (p = 0.06).
  
  
  CONCLUSIONS
  These preliminary findings demonstrate that PIT can restore glucose disposal and insulin sensitivity and partially correct glucose effectiveness and FFAd.
authors.affiliation: Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, WI 53792-7375, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hirsch
authors.forename: J
authors.initials: J
authors.lastname: Odorico
authors.forename: N
authors.initials: N
authors.lastname: Radke
authors.forename: M
authors.initials: M
authors.lastname: Hanson
authors.forename: J S
authors.initials: JS
authors.lastname: Danobeitia
authors.forename: D
authors.initials: D
authors.lastname: Hullett
authors.forename: R
authors.initials: R
authors.lastname: Alejandro
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: L A
authors.initials: LA
authors.lastname: Fernandez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000601:surgery; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose