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 language | English |
|---|---|
| Pages (from-to) | 994-1003 |
| Number of pages | 10 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2010 |
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Keywords
- Glucose metabolism
- Insulin resistance
- Insulin secretion
- PIT
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
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 journal › Article
}
TY - JOUR
T1 - Correction of insulin sensitivity and glucose disposal after pancreatic islet transplantation
T2 - Preliminary results
AU - Hirsch, D.
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.
PY - 2010/11/1
Y1 - 2010/11/1
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.
AB - 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.
KW - Glucose metabolism
KW - Insulin resistance
KW - Insulin secretion
KW - PIT
UR - http://www.scopus.com/inward/record.url?scp=77957280701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957280701&partnerID=8YFLogxK
U2 - 10.1111/j.1463-1326.2010.01290.x
DO - 10.1111/j.1463-1326.2010.01290.x
M3 - Article
C2 - 20880346
AN - SCOPUS:77957280701
VL - 12
SP - 994
EP - 1003
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 11
ER -