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

• Published in: Diabetes, obesity & metabolism Vol. 12; no. 11; pp. 994 - 1003
• Main Authors: Hirsch, D, Odorico, J, Radke, N, Hanson, M, Danobeitia, J.S, Hullett, D, Alejandro, R, Ricordi, C, Fernandez, L.A
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2010; Blackwell Publishing Ltd; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - surgery; Fatty Acids, Nonesterified; Fatty Acids, Nonesterified - physiology; Female; Glucose; Glucose - metabolism; Glucose tolerance; Glucose Tolerance Test; Humans; Immunological tolerance; Immunosuppression; Insulin; Insulin - metabolism; Insulin - physiology; Insulin resistance; Insulin Resistance - physiology; Insulin Secretion; Islet cells; Islets of Langerhans Transplantation; Islets of Langerhans Transplantation - methods; Male; metabolism; methods; Middle Aged; Pancreas transplantation; Pancreatic islet transplantation; physiology; physiopathology; PIT; secretion; surgery; Transplants & implants; Treatment Outcome; Young Adult
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01290.x

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 (Sg) and free fatty acid dynamics (FFAd) before and after PIT. Methods: Insulin sensitivity index (Si), Sg 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 Si and Sg were 3.5 ± 0.8 x 10⁻⁵/min/(pmol/l) and 0.74 ± 0.24 x 10⁻²/min, respectively. Si was significantly lower than matched NDCs [10.8 ± 0.6 x 10⁻⁵/min/(pmol/l), p < 0.004]; Sg did not reach statistical significance (1.27 ± 0.22 x 10⁻²/min, p = 0.25). Compared to pretransplant values, mean post-transplant Si and Sg were 9.6 ± 1.3 x 10⁻⁵/min/(pmol/l)and 1.28 ± 0.22 x10⁻²/min, respectively, indicating significant improvement for Si but not Sg (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.