University of Illinois at Chicago
Improvements in multiple cardiovascular biomarkers following islet cell transplantation in patients with type 1 diabetes
Kirstie K. Danielson1,2, Safa Farid1, Rebecca S. Monson1, Jose Oberholzer1, Wesley Schrock1.
1Division of Transplant Surgery, University of Illinois at Chicago, Chicago, IL, United States; 2Division of Epidemiology & Biostatistics, University of Illinois at Chicago, Chicago, IL, United States
Background: Ischemic heart disease is the principal cause of mortality in type 1 diabetes (T1D), with the burden being substantially greater for women than for men with T1D. Long-term improvements in T1D complications following islet cell transplantation, including risk factors for cardiovascular disease, are not completely understood. Our previous research demonstrated significant decreases in carotid intima-media thickness following islet transplantation, potentially indicating an improvement in cardiovascular health, even with the known negative effects of immunosuppression on lipid levels and blood pressure. To further investigate the impact of islet transplant on cardiovascular health, we evaluated changes in several cardiovascular biomarkers after islet transplantation in men and women with T1D.
Methods: The analysis includes 27 patients with T1D who were enrolled in the University of Illinois at Chicago’s phase 1/2 (n=10) and phase 3 (n=17) islet transplantation clinical trials. Each patient received 1-3 islet transplants to achieve glucose control. Data were available both pre- and post-transplant (from 1 week to 10 years) resulting in a total of 155 longitudinal time points across all patients. Blood pressure and cardiovascular biomarkers (e.g., lipids, inflammatory markers, and coagulation factors) were serially collected. Changes following transplant were determined using multivariable linear regression of repeated measures, adjusting for recipient age, sex, body mass index (BMI), clinical trial phase, number of transplants, immunosuppressive regimen, and use of statins and antihypertensive medications. Effect modification by patient sex on any biomarker changes following transplant was investigated.
Results: Recipients included 6 males and 21 females with a mean age=47.3 years and BMI=22.4. In the total sample, following transplant high-density lipoprotein (HDL; p=0.005), apolipoprotein A-1 (apo A-1; p=0.002), and plasminogen activator inhibitor-1 (PAI-1) antigen (p=0.02) increased, while triglycerides (p=0.04), fibrinogen (p<0.0001), and PAI-1 activity (p<0.0001) decreased. The increases in HDL and apo A-1 were significantly greater for females than males (interaction p≤0.05), whereas the decrease in total cholesterol was significantly greater for males than females (interaction p=0.03). Blood pressure and other factors such as free fatty acids, C-reactive protein (CRP), and vascular cell adhesion modelcule-1 (VCAM-1) did not change. Importantly, none of the cardiovascular biomarkers worsened after islet transplant.
Conclusion: Our findings suggest that islet transplantation may have beneficial cardiovascular effects, by improving the lipid and coagulation profiles for patients with T1D, despite the long-term use of immunosuppressive medications. Interestingly, the improvements in lipids differed by patient sex where HDL increased for females and total cholesterol decreased for males. The changes in PAI-1 antigen and activity are also consistent with improved cardiovascular health. Further research is needed to determine if these biomarker changes translate into better clinical cardiovascular outcomes for both men and women after islet transplant.
11:00 - 12:30
|Trends and progress in clinical islet transplantation||Improvements in multiple cardiovascular biomarkers following islet cell transplantation in patients with type 1 diabetes||Plenary Room 1|
11:00 - 12:30
|Pancreas and Islet Transplantation: Imaging, Biopsies, and Biomarkers||Higher baseline levels of the bone hormone undercarboxylated osteocalcin independently predict improved islet cell transplantation outcomes||Room 110|