4) DIABETES AND HEART DISEASE
g) Blood Proteins, Diabetes and Heart Disease
A person with diabetes has an increased sensitivity to the normal risk factors for heart disease, even if the person with diabetes controls his blood sugar levels very well. It turns out that this increased sensitivity may be due to a common causal factor for both diabetes and heart disease. This common causal factor appears to be a blood protein involved in the blood clotting mechanism. This protein is vital to the functioning of one of the two pathways by which blood clots. Take it away and clotting occurs very slowly. Give too much of it, and clotting occurs too easily. Research by De Taeye B, Smith LH, Vaughn DE, of Vanderbilt University Medical Center and others has established that excess amounts of this "PAI-1" protein appears to be a factor in both heart disease and type 2 diabetes. PAl-1 levels appear to be at least partially genetically determined but it is also related to the amount of exercise one gets, obesity and the diet one consumes. There also appears that increased levels of PAl-1 are directly related to mid-section fat and to increased insulin insensitivity.
PAl1 impacts many different bodily functions, almost always in a negative fashion. Increased PAI-1 levels are associated with increased risk of:
1, First Heart Attacks (Circulation 1998;98:2241-7)
2, Death in patients with stable angina pectoris (Circulation 1997 ;95:2380-6)
3, Continued progression of heart disease and death after a heart attack (Eur Heart J 1998;19)(Lancet 1987;2:) (CABG; J Cardiovasc Surg [Torino] 2001;42) (Circulation 2003;108)
4, Early mortality following stroke (Thromb Haemost 1997 77:730-4)
5, Development of type 2 diabetes (Diabetes 2002;51:1131-7)High PAl-1 levels increase the tendency of blood to clot, appear to increase blood lipids and appear to cause diabetes, which causes proteins to be poisoned (glycation). Put it all together and high PAl-1 levels are a really bad actor. The only thing PAl-1 seems to prevent is the type of stroke which bleeds into the brain (hemorrhagic stroke), which only constitutes 12% of all strokes. Most strokes are ischemic strokes caused by blood clots, many of which are produced by bad blood chemistry, namely excess levels of PAl-1, cholesterol and triglycerides. It appears that PAl-1 was designed by evolution for a time when serious cuts and bleeding were an everyday part of life (i.e. Paleolithic times) and clotting served a much more important function than it does in the modern world.
It appears to be beneficial for any individual to reduce this PAI-1 blood protein. PAI-1 levels are reduced by a wide range of interventions including lifestyle modification (proper exercise, weight loss and diet) and pharmacological therapy with oral antihyperglycaemic agents (e.g. thiazolidinediones used to treat diabetes, Avandia™ and Actos™), fibrates, statins (such a Lipitor, used to treat high cholesterol), ACE inhibitors (used for high blood pressure), angiotensin II type-1 receptor-blockers (also used for high blood pressure) and hormone replacement therapy (HRT). These interventions can reduce PAI-1 by 30 to 60%. Note that control of blood sugar is NOT on the list of things which control PAl-1; this may be why simply controlling blood sugar is not very effective in improving life expectancy for a person with diabetes. The excess PAl-1 will give the person with diabetes heart disease even if they control their blood sugar. Blood sugar levels alone appear to account for only 20% to 30% of large blood vessel disease complications seen with type 2 diabetes.
There are also other blood proteins which seem to be involved in both type 2 diabetes and heart disease. These abnormal "inflammatory" blood proteins are invariable present in both diabetes and heart conditions. Many researchers think these proteins cause both diabetes and heart disease while other researchers feel the proteins are the result of both diseases. What is clear is the strong link between the process that creates type 2 diabetes and the process that creates heart disease, whatever the role of the proteins.
Current Chapter: 4) DIABETES AND HEART DISEASE
a) Introduction
b) Small Blood Vessel versus Large Blood Vessel Disease
c) Large Blood Vessel Mechanisms
d) Blood Lipid Chemistry
e) Diabetes and "Heart Failure"
f) Peripheral Arterial Disease (PAD)
g) Blood Proteins, Diabetes and Heart Disease
h) Genetic Risk Factors for Diabetes and Heart Disease
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