Cardiovascular Disease
- AMI, acute myocardial infarction
- AMPK, AMP-activated protein kinase
- CABG, coronary artery bypass graft
- CHD, coronary heart disease
- CHF, congestive heart failure
- CVD, cardiovascular disease
- DIGAMI, Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction
- FFA, free fatty acid
- GIK, glucose-insulin-potassium
- ICU, intensive care unit
- KATP channel, ATP-sensitive K+ channel
- NMR, nuclear magnetic resonance
- SUR, sulfonylurea receptor
- UGDP, University Group Diabetes Program
- UKPDS, U.K. Prospective Diabetes Study
This is the sixth in a series of articles on presentations at the American Diabetes Association Annual Meeting, San Diego, California, 10–14 June 2005.
Glycemia, insulin treatment, and cardiovascular disease
Animal models.
Many presentations at the ADA meeting addressed aspects of the relationship between diabetes and cardiovascular disease (CVD). Karin Bornfeldt (Seattle, WA) described evidence from mouse models, suggesting that dyslipidemia accounts for most of lesion formation and progression, while hyperglycemia appears to accelerate additional phases of plaque formation. A number of studies have utilized models of hyperglycemia without dyslipidemia, with inconsistent evidence of adverse effect. In contrast, animal models with both hyperglycemia and hyperlipidemia show consistent increase in atherosclerosis. In the LDL receptor–deficient mouse with autoimmune type 1 diabetes and fairly severe hyperglycemia compared with an intensively insulin-treated group, VLDL triglyceride and cholesterol levels were similar to control on a low-fat diet but elevated to levels above those in nondiabetic controls on a high-fat diet. Atherosclerotic lesion initiation was approximately twice that in both the nondiabetic and insulin-treated groups, in both the high-fat and low-fat diet groups, but the nondiabetic baseline atherosclerosis level was considerably greater on the high-fat diet. The lesions in the nonhyperlipidemic animals are macrophage-containing fatty streaks, reflecting increased recruitment of macrophages into the arterial wall, while in the high-fat diet group, there was also increased macrophage proliferation in the arterial wall, as well as increased hyaluronan deposition, with the lipid abnormality appearing to drive lesion formation. In a subsequent study, animals were fed a high-fat diet for 4 months and then changed to a low-fat diet with or without induction of diabetes, with diabetes not in itself associated with major lipid abnormality. Plaque progression was actually reduced in the diabetic model, and lesion morphology was similar to that in the nondiabetic group.
Ross Gerrity (Augusta, GA) described evidence from porcine models with hypercholesterolemia …
