Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation: Preliminary results

Aims: 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 = 0.008and 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).Conclusion: These preliminary findings demonstrate that PIT can restore glucose disposal and insulin sensitivity and partially correct glucose effectiveness and FFAd.