BOD L7 Diabetes in CVD Flashcards
Have an awareness of epidemiological studies linking type 2 diabetes and CVD. Understand the molecular mechanisms that increase the risk of CVD in type 2 diabetics
What is the major cause of death or type 2 diabetics?
Coronary artery disease.
Higher risk of developing cerebrovascular disease and peripheral vascular disease.
What risk factors are of CVD in diabetic patients? How can these be treated?
Increased [LDL] - treated with statins
Decreased [HDL]
High blood pressure - treated with ACE inhibitors or diuretics)
Smoking
Hyperglycaemia (sulphonylureas, biguanides)
How can insulin resistance occur via obesity?
Adipocytes (Fat cells) release pro-inflammatory adipocytokines, which decrease insulin sensitivity by disrupting glucose uptake.
This is insulin resistance - major trigger.
Happens due to excess abdominal fat (large waistline). Known as central/abdominal obesity, particularly high-risk form of obesity.
What occurs in obesity that could promote endothelial dysfunction?
Role of some adipocytokines
- Leptin
- TNFalpha
- IL-6
- Adiponectin
Lipoprotein profile in obesity
- LDL increase
What paradox is seen regarding leptin in obesity?
Leptin is responsible for decreaase in appetite. Produced by adipocytes to let body know that enough energy in fat stores to prevent overeating.
Paradoxically obese people have high serum leptin. This is explained by mutations in leptin receptors, and leptin resistance.
Leptin receptors in brain are a member of what signalling molecule receptor?
Class I cytokine receptors.
Where in brain does leptin bind?
What does this cause?
Binds to arcuate nucleus.
Stimulates production of catabolic neuropeptides (such as POMC).
Suppresses release of anabolic neuropeptides, leading to reduction in appetite.
What role does TNFalpha play in obesity?
Levels are found increased in the adipose tissue with obesity. It inhibits adipocyte differentiation, and stimulates lipid metabolism.
Reduces bioavailability of NO.
What role does IL-6 play in obesity?
Produced in many cells, but 1/3 of circulating IL-6 derived from adipose tissue.
IL-6 increases in blood causes:
expression of adh. molecules and secretion of cytokines by endo. cells.
Secretion of MCP-1 from macrophages.
Smooth muscle cell proliferation and migration.
Tissue factor expression.
Platelet production and aggregation.
High levels found in atherosclerotic lesions.
What role does adiponectin play in obesity?
Its level is reduced in obesity.
Metabolic effect is increases fatty acid oxidation,
Increases GLUT4. A glucose transporter in skeletal muscle, responsible for removal of glucose from blood.
Adiponectin secretion is decreased by TNF and IL-6.
What is GLUT4?
Glucose transporter in skeletal muscle. Translocates to cell surface on muscle cells in response to insulin to absorb glucose from blood.
What effect does diabetes have on lipoprotein profile?
Evevated triglycerol, increased LDL, lowered HDL.
This is because
Insulin decreases VLDL secertion,
Increases LDL.
Increases HDL synthesis
What effect does dietary saturated fatty acids have on plasma cholesterol?
Increases
What should SFA be replaced with in the diet to reduce [LDL]
Polyunsaturated fatty acids.
What happens to plasma cholesterol by action of omega 3?
VLDL reduction
HDL cholesterol increase
amongst other things, ApoB, Stearoyl CoA desturase, LDL receptor gene expression
