Reduction in carotid intima-media thickness after pancreatic islet transplantation in patients with type 1 diabetes

Abstract

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 DESIGNAND METHODS-Consecutive case series of 15adults (mean age [SD], 49 years [10 years]; 87% female) with type 1 diabetes for ≥5 years (mean duration [SD], 30 years [12 years]; mean HbA1c [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 12months (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 HbA1c, 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.© 2013 by the American Diabetes Association.