We continue our articles on cardiovascular disease with this article on another aspect of the problem that has great significance for diabetics. Arteriosclerosis is the general term for thickening and hardening of the arteries. This occurs normally as we age. Atherosclerosis is a type of arteriosclerosis, and is characterized by deposits of fatty substances, cholesterol, cellular waste products, calcium, and fibrin in the inner lining of the arteries.
This buildup is called plaque. Plaque can partially or totally block the flow of blood through an artery. When plaque occurs two things can happen: hemorrhaging into the plaque and/or formation of a clot or thrombus on the plaque’s surface. If either of these occurs and blocks the entire artery, a heart attack or stroke may result.
Atherosclerosis is a slow, progressive disease, and if you have been reading research on the subject, you know that the process has been found to begin in children and adolescents. It affects large and medium sized arteries, but the type of artery and the progressive time table appear to vary with the individual.
The development of atherosclerosis is complex and the exact causes are not completely understood, but most scientists believe that it begins because the inner lining of the artery, the endothelium, becomes injured to the point that it can no longer do its job. When this occurs, over time, fats, cholesterol, and other substances may pass through the damaged lining and become deposited in the artery wall.
These other substances are oxidized forms of cholesterol-carrying fats, called oxidized lipoproteins which cause the artery walls to make more cell buildup in the endothelium where the atherosclerotic lesions form. These cells, which are often white cells normally found in the blood, and cells found in the artery wall, accumulate, and many of them divide.
At the same time fat cells continue to build up in and around these cells. They form connective tissue and thus the endothelium becomes thicker and thicker. As this occurs, the deposit can reduce the blood flow through the artery, and oxygen supply to the heart, brain, or limbs causing heart attack, stroke, or gangrene.
There are three postulated causes for damage to the arterial walls in the general public: elevated levels of cholesterol and triglycerides, high blood pressure, and cigarette smoking. Both type 1 and type 2 diabetes carry an increased risk for the development of atherosclerosis above and beyond these other risk factors.
Cholesterol is a soft, fat-like substance found in the body’s cells. It forms cell membranes, certain hormones and other necessary substances. The body produces about 1000 mg a day. In addition, what you eat can add to this in the form of fats from animals, especially egg yolks, meat, fish, poultry, and whole milk dairy products.
Typically, the body makes all the cholesterol it needs to maintain health. Beside being found in the body’s cells, cholesterol is also present in the blood stream where it is transported to various parts of the body. Hypercholesteremia is the medical term used when high levels of cholesterol are found in the blood.
Cholesterol and triglycerides cannot dissolve in the blood stream, and must be transported by carriers called lipoproteins, which are created in the liver. The process starts when cholesterol and fats in foods are digested in the intestine, Chylomicrons (fatty particles containing mainly triglycerides, but also cholesterol, phospholipids, and protein) are produced in the intestinal wall.
When the chylomicrons enter the blood stream, they connect to binding sites on capillaries. Many of the triglycerides break down and are released into the blood stream. The remainder, now richer in cholesterol, continues circulating until it reaches the liver and is absorbed.
The liver then produces very low density lipoprotein (VLDL), the largest lipoprotein which carries triglycerides made in the liver from fatty acids, carbohydrates, alcohol, and some cholesterol into the blood stream. Like chylomicrons, is the VLDL transported to the capillaries where the triglycerides are broken down and either used for energy or stored by muscle or fat cells.
After VLDL releases triglycerides, what remains is called intermediate density ipoprotein (IDL), some of which is removed from circulation by the liver. The rest is transformed into low density lipoprotein (LDL). LDL is the major cholesterol carrier in the blood carrying 60 to 80 % of the body’s cholesterol.
Some of this circulating cholesterol is used to build cells, some is returned to the liver, and if there is too much circulating in the blood stream, it may also be deposited in artery walls. This tendency of LDL to produce arterial deposits has given rise to its name of “bad” cholesterol, and why lower levels of LDL reflect a reduced risk of heart disease.
Another type of lipoprotein is high density lipoprotein (HDL), which is a flat, disc-like particle produced primarily in the liver and intestines and then released into the blood-stream. As VLDL and chylomicron particles release their triglycerides into the body cells, fragments containing proteins, fats, and cholesterol break away.
It is thought that HDL picks up cholesterol and transports it back to the liver for reprocessing or excretion. It is also thought that HDL removes excess cholesterol from fat-sated cells, possibly even those in artery walls. Because it clears cholesterol from the system, and high levels are associated with decreased risk of heart disease, HDL is often called “good” cholesterol. The levels of HDL and LDL in the blood are measured to evaluate the risk for atherosclerosis.
As we age our levels of triglycerides and cholesterol tend to rise. Some studies suggest that raised triglycerides are present in people with coronary heart disease, while there are also people with hypertriglyiceridemia (raised triglycerides) who are free from atherosclerosis. Elevated triglycerides are thought, at the least, to accompany other abnormalities that speed the development of coronary heart disease which is why it is most often measured with LDL and HDL.
The importance of treating dyslipidemia in type 2 diabetics is linked to an associated two to fourfold excess risk of coronary heart disease. There are also findings that the increased cardiovascular risk factors exist before the onset of type 2 diabetes. The most common pattern of dyslipidemia in type 2 diabetes is elevated triglycerides and decreased HDL levels.
Diabetics may also have elevated levels of LDL and VLDL; however, type 2 diabetic patients typically have more smaller, denser LDL particles, which possibly increases atherogenicity, even if the absolute concentration of LDL is not significantly increased. There are few studies of lipids and lipoproteins as predictors of CHD in type 2 diabetics with somewhat contradictory results, but in observational studies HDL may be the best predictor of CHD in type 2 diabetes followed by triglycerides and total cholesterol.
Furthermore, the results from clinical trials and observational studies in diabetic subjects are somewhat inconsistent in that LDL lowering has been beneficial in clinical trials but not a significant predictor in observational studies. But since the former provide stronger data, the emphasis is placed on lowering LDL but should include interventions to also lower triglyceride levels and raise HDL levels.
The ADA recommends medical, nutritional therapy and exercise for treating dyslipidemia. Weight loss and increased physical activity leads to decreased triglycerides and increased HDL cholesterol levels and to modest lowering of LDL They suggest a lowering of the percentage of saturated fat in the diet and an increase of carbohydrates or monounsaturated fats to compensate for the reduction of saturated fat.
Recommendations of the American Heart Association for patients with CHD suggest that the maximum change from a medical nutritional plan is 15 to 25 mg/dl, so they may decide on a dual approach including pharmacological therapy at the same time as behavioral therapy for high risk groups. Because of the frequent changes in glycemic control in diabetic patents and the effects of those changes on levels of lipoprotein, levels of LDL, HDL, total cholesterol, and triglycerides, the problem of control risk factors for CHD are compounded.
For this reason these should be tested at least once a year until glycemic control is obtained and maintained. Optimal LDL cholesterol levels for adults with diabetes are <100mg/dl, optimal HDL cholesterol levels are >45 mg/dl, and desirable triglyceride levels are <200 mg/dl.
The results of research indicates that aggressive therapy of diabetic dyslipidemia in type 2 diabetics will most probably reduce the risk of CHD. Primary therapy should be directed at lowering LDL levels. Because there is limited data available from clinical trial in diabetic patients, the high incidence of mortality for diabetic patients with first myocardial infarction, it is necessary to treat dyslipidemia aggressively with pharmacological intervention.
In persons with multiple risk factors, intervention trying to return to normal level is suggested when LDL levels are between 100 and 130 mg/dl. The initial therapy for hypertriglyceridemia is improved glycemic control, but pharmacological intervention may be necessary for additional lowering of triglyceride levels.
Type 1 diabetics in good control tend to have normal, and sometimes better than normal levels of lipoprotein. Their composition of lipoproteins may be abnormal but the effects of these abnormalities on CHD are unknown.
Again, as in type 2 diabetes, there is relatively little observational data on lipoproteins and CHD and there are no clinical trials relating lipoproteins and CHD. Experts agree that it is reasonable that if type 1 diabetics have LDL levels that are above the goals recommended for type 2 diabetics, they should be aggressively treated. Improved glycemic control may be even more important in type 2 diabetics than in type 2 for reduction of CHD, as has been proved by research