posted on 2013-12-03, 00:00authored byKirstie K. Danielson, Betul Hatipoglu, Katie Kinzer, Bruce Kaplan, Joan Martellotto
OBJECTIVE Determine the impact of islet transplantation on carotid intima-media thickness (CIMT), a marker for atherosclerosis, in type 1 diabetes without kidney disease. RESEARCH DESIGN AND METHODS Consecutive case series of 15 adults (mean age [SD], 49 years [10 years]; 87% female) with type 1 diabetes for ≥5 years (mean duration [SD], 30 years [12 years]; mean HbA(1c) [SD], 7.2% [0.9%]), without kidney disease, presenting with severe hypoglycemic unawareness to undergo allogeneic pancreatic islet transplant(s) (one to three each) in a phase 1/2 and 3 clinical trial. Current follow-up ranges from 1 to 5 years (2005-2011). CIMT of the common and internal carotid arteries was measured before and every 12-16 months after the first transplant (two to six CIMTs each) by one ultrasonographer and one blinded reader. CIMT was analyzed as change from baseline to 12- and 50-month follow-up; a combined CIMT score was calculated as the sum of the standardized IMT scores (SD units [SDs]) of both arteries. RESULTS All patients achieved insulin independence after one to three transplants. CIMT decreased at 12 months (n = 15) for the common carotid (-0.058 mm; P = 0.006) and combined score (-1.28 SDs; P = 0.004). In those with 50-month follow-up (n = 7), the decrease in the combined score continued from 12 (-1.59 SDs; P = 0.04) to 50 months (-0.77 SDs; P = 0.04). During follow-up, the decreasing slope of change in CIMT was associated with decreasing slopes of change in HbA(1c), lipoproteins, and cardiovascular/inflammatory markers. CONCLUSIONS Islet transplantation may ameliorate diabetes-related atherosclerosis through improved glycemic control consequent to restoring endogenous insulin secretion, and optimal lipid management posttransplant also contributes.
Funding
NCRR (NIH islet cell resource grant U42 RR023245).
History
Publisher Statement
This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version in print and online at http://diabetes.diabetesjournals.org.