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

D. Hirsch, J. Odorico, N. Radke, M. Hanson, J. S. Danobeitia, D. Hullett, Rodolfo Alejandro, Camillo Ricordi, L. A. Fernandez

Research output: Contribution to journalArticle

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Abstract

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 × 10-5/min/(pmol/l) and 0.74 ± 0.24 × 10-2/min, respectively. Si was significantly lower than matched NDCs [10.8 ± 0.6 × 10-5/min/(pmol/l), p < 0.004]; Sg did not reach statistical significance (1.27 ± 0.22 × 10-2/min, p = 0.25). Compared to pretransplant values, mean post-transplant Si and Sg were 9.6 ± 1.3 × 10-5/min/(pmol/l)and 1.28 ± 0.22 ×10-2/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.

Original languageEnglish
Pages (from-to)994-1003
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2010

Fingerprint

Islets of Langerhans Transplantation
Insulin Resistance
Glucose
Nonesterified Fatty Acids
Insulin
Transplants
Graft Survival
Glucose Tolerance Test
Type 1 Diabetes Mellitus
Immunosuppression

Keywords

  • Glucose metabolism
  • Insulin resistance
  • Insulin secretion
  • PIT

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hirsch, D., Odorico, J., Radke, N., Hanson, M., Danobeitia, J. S., Hullett, D., ... Fernandez, L. A. (2010). Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation: Preliminary results. Diabetes, Obesity and Metabolism, 12(11), 994-1003. https://doi.org/10.1111/j.1463-1326.2010.01290.x

Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation : Preliminary results. / Hirsch, D.; Odorico, J.; Radke, N.; Hanson, M.; Danobeitia, J. S.; Hullett, D.; Alejandro, Rodolfo; Ricordi, Camillo; Fernandez, L. A.

In: Diabetes, Obesity and Metabolism, Vol. 12, No. 11, 01.11.2010, p. 994-1003.

Research output: Contribution to journalArticle

Hirsch, D. ; Odorico, J. ; Radke, N. ; Hanson, M. ; Danobeitia, J. S. ; Hullett, D. ; Alejandro, Rodolfo ; Ricordi, Camillo ; Fernandez, L. A. / Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation : Preliminary results. In: Diabetes, Obesity and Metabolism. 2010 ; Vol. 12, No. 11. pp. 994-1003.
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AU - Odorico, J.

AU - Radke, N.

AU - Hanson, M.

AU - Danobeitia, J. S.

AU - Hullett, D.

AU - Alejandro, Rodolfo

AU - Ricordi, Camillo

AU - Fernandez, L. A.

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N2 - 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 × 10-5/min/(pmol/l) and 0.74 ± 0.24 × 10-2/min, respectively. Si was significantly lower than matched NDCs [10.8 ± 0.6 × 10-5/min/(pmol/l), p < 0.004]; Sg did not reach statistical significance (1.27 ± 0.22 × 10-2/min, p = 0.25). Compared to pretransplant values, mean post-transplant Si and Sg were 9.6 ± 1.3 × 10-5/min/(pmol/l)and 1.28 ± 0.22 ×10-2/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.

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