Hatipoglu, Betul, Uy, Arleen, Naing, Soe, Martellotto, Joan, Barbaro, Barbara, Salehi, Payam, Gangemi, Antonio, Kuechle, Joseph, Benedetti, Enrico, Kaplan, Bruce, and Oberholzer, Jose
Cardiovascular disease is highly prevalent in diabetic patients. Inflammation and dyslipidemia play an important role in diabetic atherogenesis, likely related to chronic hyperglycemia. We examined the effect of islet transplantation and immunsuppression on inflammation and lipid profiles, as well on the progression of carotid artery intima-media thickness (CIMT). Ten type 1 diabetic patients with hypoglycemic unawareness underwent islet transplantation between 2005 and 2006. The duration of DM was 28±10 years and the mean age 47±11 years. Pretransplant HbA1c was 6.9±0.8% and fructosamine 297±44 umol/L. We compared body weight, blood pressure, lipids and inflammatory markers before and 6 months after the last islet transplant. CIMT was measured by ultrasound before and 64 weeks after islet transplantation (n=7). Insulin independence was achieved in all patients, and maintained in 8 patients for more than 64 weeks. Weight decreased from 138±10 lb to 127±12 (p=0.0007), BMI from 22.5±1.2 to 21.6±1.5 p=0.05. The HbA1C and fructosamine decreased to 5.8±0.3% (p=0.01) and 245±37 umol/L (p=0.01). Systolic blood pressure increased from 122±13 mm Hg to 133±18 p=-0.1, diastolic from 70±12 mmHg to 73±7 p=0.5. Lipids tented to increase non-significantly, LDL from 88±25 mg/dL to 99±38 mg/dL p=0.3, HDL from 60.9±17 mg/dL to 57±22 mg/dL p= 0.3, TG from 91±86 mg/dL to 124±46 mg/dL p=0.1. The following inflammatory markers showed a significant decrease: MMP-9 decreased from 358±173 to 155±55 ng/mL (p=0.0066), MCP-1 127±44 pg/mL to 80±29 (p=0.0056). No significant changes were found in the concentrations of FFA, PAI-1 antigen, fibrinogen, CRP, tPA, ICAM-1, VCAM-1 and PAI-activity, as well as microalbuminuria. The CIMT decreased significantly from 0.825 ± 0.139 mm to 0.732±0.077 mm (p=0.03) after 16 months of follow up. In conclusion, we observed a significantly improved glycemic control, associated with significant reduction in some inflammatory markers (MMP-9 and MCP), while other cardiometabolic risk factors (lipids, blood pressure) worsened likely as a consequence of tacrolimus and sirolimus. However, we observed a significant reduction in CIMT, which is a strong indicator of an overall benefit of islet transplantation on cardiovascular disease progression. [ABSTRACT FROM AUTHOR]