Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes

Brett Rydzon, Rebecca S. Monson, Jose Oberholzer, Krista A. Varady, Melena D Bellin, Kirstie K. Danielson

Research output: Contribution to journalArticle

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Abstract

Background: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. Methods: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis; 95 observations). Results: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P =.02), then stabilized (P =.39); HOMA-IR remained stable posttransplant (P =.92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (P =.03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both P ≤.04) and also with higher exenatide dose (both P ≤.01). More islets transplanted were associated with higher SIis (P <.0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤.01). Conclusions: Insulin sensitivity measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

Original languageEnglish (US)
Article numbere2972
JournalDiabetes/Metabolism Research and Reviews
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2018

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Type 1 Diabetes Mellitus
Islets of Langerhans
Insulin Resistance
Transplants
RANK Ligand
Leptin Receptors
Phase III Clinical Trials
Clinical Trials, Phase I
C-Peptide
Leptin
Fasting
Homeostasis
Biomarkers
Exercise
Diet
Bone and Bones

Keywords

  • exenatide
  • insulin sensitivity
  • islet cell transplantation
  • leptin
  • receptor activator of nuclear factor kappa-B ligand (RANKL)
  • type 1 diabetes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes. / Rydzon, Brett; Monson, Rebecca S.; Oberholzer, Jose; Varady, Krista A.; Bellin, Melena D; Danielson, Kirstie K.

In: Diabetes/Metabolism Research and Reviews, Vol. 34, No. 3, e2972, 01.03.2018.

Research output: Contribution to journalArticle

Rydzon, Brett ; Monson, Rebecca S. ; Oberholzer, Jose ; Varady, Krista A. ; Bellin, Melena D ; Danielson, Kirstie K. / Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes. In: Diabetes/Metabolism Research and Reviews. 2018 ; Vol. 34, No. 3.
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T1 - Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes

AU - Rydzon, Brett

AU - Monson, Rebecca S.

AU - Oberholzer, Jose

AU - Varady, Krista A.

AU - Bellin, Melena D

AU - Danielson, Kirstie K.

PY - 2018/3/1

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N2 - Background: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. Methods: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis; 95 observations). Results: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P =.02), then stabilized (P =.39); HOMA-IR remained stable posttransplant (P =.92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (P =.03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both P ≤.04) and also with higher exenatide dose (both P ≤.01). More islets transplanted were associated with higher SIis (P <.0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤.01). Conclusions: Insulin sensitivity measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

AB - Background: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. Methods: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis; 95 observations). Results: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P =.02), then stabilized (P =.39); HOMA-IR remained stable posttransplant (P =.92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (P =.03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both P ≤.04) and also with higher exenatide dose (both P ≤.01). More islets transplanted were associated with higher SIis (P <.0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤.01). Conclusions: Insulin sensitivity measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

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KW - receptor activator of nuclear factor kappa-B ligand (RANKL)

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