BADERC Welcome

Mark Creager, M.D.

Atherosclerosis in Diabetes

Atherosclerosis is a major cause of death and disability in patients with diabetes mellitus. Endothelial dysfunction is an important factor in atherogenesis. Basic research has increased our understanding of the mechanisms that impair vascular function in patients with diabetes. Dr. Creager’s laboratory is engaged in translational studies to extend these observations to humans. Using techniques that examine vascular function in humans, he and his colleagues found that hyperglycemia, per se, induces abnormal endothelium-dependent vasodilation via oxidative stress and abnormalities in intracellular signaling mediated by PKCβ. His research group is currently evaluating the effect of insulin resistance on vascular function in patients with diabetes mellitus. Specifically, the laboratory is looking at the contribution of inflammation and free-fatty acids to insulin-nitric oxide signaling. Dr. Creager and colleagues are also conducting studies to determine whether insulin resistance contributes to the pathophysiology of claudication in patients with peripheral arterial disease. Findings from these studies will have important implications regarding the pathogenesis of vascular disease in diabetes and may lead to treatment strategies to reduce vascular complications in this population. Co-investigators and collaborators who are participating in these studies include Dr. Joshua Beckman and Dr. Allison Goldfine.

References:

Beckman JA, Goldfine AB, Gordon MB, Creager MA. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001;103:1618-1623.
Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA. Inhibition of protein kinase Cß prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res. 2002;90:107-111.
Nohria A, Garrett L, Johnson W, Kinlay S, Ganz P, Creager MA.Endothelin-1 and vascular tone in subjects with atherogenic risk factors. Hypertension. 2003;42:43-8.
Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF Jr, Creager MA. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2003 ;285:H2392-8.5.
Beckman JA, Goldfine A, Dunaif A, Gerhard-Herman M, Creager MA. Endothelial function varies according to insulin resistance type. Diabetes Care 2007;30:1226-1232.
Pande RL, Perlstein TS, Beckman JA, Creager MA. Association of insulin resistance and inflammation with peripheral arterial disease: the National Health and Nutrition Examination Survey, 1999-2004. Circulation. 2008;118:33-41.






			Mark Creager, M.D. Atherosclerosis in Diabetes Atherosclerosis is a major cause of death and disability in patients with diabetes mellitus. Endothelial dysfunction is an important factor in atherogenesis. Basic research has increased our understanding of the mechanisms that impair vascular function in patients with diabetes. Dr. Creager’s laboratory is engaged in translational studies to extend these observations to humans. Using techniques that examine vascular function in humans, he and his colleagues found that hyperglycemia, per se, induces abnormal endothelium-dependent vasodilation via oxidative stress and abnormalities in intracellular signaling mediated by PKCβ. His research group is currently evaluating the effect of insulin resistance on vascular function in patients with diabetes mellitus. Specifically, the laboratory is looking at the contribution of inflammation and free-fatty acids to insulin-nitric oxide signaling. Dr. Creager and colleagues are also conducting studies to determine whether insulin resistance contributes to the pathophysiology of claudication in patients with peripheral arterial disease. Findings from these studies will have important implications regarding the pathogenesis of vascular disease in diabetes and may lead to treatment strategies to reduce vascular complications in this population. Co-investigators and collaborators who are participating in these studies include Dr. Joshua Beckman and Dr. Allison Goldfine. References: Beckman JA, Goldfine AB, Gordon MB, Creager MA. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001;103:1618-1623. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA. Inhibition of protein kinase Cß prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res. 2002;90:107-111. Nohria A, Garrett L, Johnson W, Kinlay S, Ganz P, Creager MA.Endothelin-1 and vascular tone in subjects with atherogenic risk factors. Hypertension. 2003;42:43-8. Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Keaney JF Jr, Creager MA. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2003 ;285:H2392-8.5. Beckman JA, Goldfine A, Dunaif A, Gerhard-Herman M, Creager MA. Endothelial function varies according to insulin resistance type. Diabetes Care 2007;30:1226-1232. Pande RL, Perlstein TS, Beckman JA, Creager MA. Association of insulin resistance and inflammation with peripheral arterial disease: the National Health and Nutrition Examination Survey, 1999-2004. Circulation. 2008;118:33-41.