WHAT’S HOT IN DIABETES: TYPE 2 DIABETESA critical issue in type 2 diabetes is the steady increase in prevalence over the past decade, particularly in developed countries. There has been an alarming increase in numbers of obese individuals and the choice of a sedentary lifestyle. It is now clear that type 2 diabetes is caused by a combination of insulin resistance and progressive insulin deficiency, and therapy must be directed at both defects. Exciting studies have now demonstrated that intensive lifestyle changes, including a regular exercise conditioning program and modest weight reduction (5-10%), will delay the onset of type 2 diabetes in those with impaired glucose tolerance. Specific methods to accomplish this, as was done in the research trials, are now widely promoted. Translation to the real world will be difficult.One of the most exciting developments in diabetes is the general acceptance by the medical community that a metabolic syndrome (previously called Syndrome X or the Insulin Resistance Syndrome) usually precedes and accompanies clinical diabetes. This syndrome has the essential components of impaired glucose tolerance (or frank diabetes), centripetal obesity, hypertension, elevated plasma triglyceride, and low plasma HDL cholesterol levels in variable combinations. Other vascular risk factors may be present, such as microalbuminuria and decreased fibrinolytic activity. A focus on prevention of future cardiovascular events in these people who often have “mild” diabetes has dramatically changed our therapeutic strategies, very early in the course of diabetes mellitus.*4\357\8*
CONTROLLING RISKS FOR CARDIOVASCULAR DISEASES: MONITOR YOUR CHOLESTEROL LEVELS If a blood test reveals that you have a high level of total cholesterol (more than 240 mg/dl), the first thing you should do is to have the test retaken to make sure that the reading is accurate. (Remember that prior to having your blood drawn, you must not eat or drink anything for 12 hours.) If your total cholesterol level still high, you should request that a lipoprotein analysis be done to determine the level of LDLs and HDLs in your blood. Lipoprotein analysis, which also requires that you fast for 12 hours, measures the level of three substances: total cholesterol, HDL, and triglycerides. The level of LDL is derived using a standard formula: LDL = Total cholesterol – HDL – (Triglycerides:5). For example, if the level of total cholesterol is 200, the level of HDL 45, and the level of triglycerides 150, the LDL level would be 125 (200 – 45 – 30).In general, LDL is more closely associated with cardiovascular risks than is total cholesterol. However, most authorities agree that by looking only at LDL, we ignore the positive effects of HDL. Perhaps the best method of evaluating risk is to examine the ratio of HDL to total cholesterol or the percentage of HDL in total cholesterol. If the percentage of HDL is less than 35, the risk increases dramatically.The ratio of HDL to total cholesterol can be controlled either by lowering LDL levels or by raising HDL levels. The best way to lower LDL levels is to reduce dietary intake of the major sources of saturated fat. However, in extreme cases medications can also be used.*12/277/5*
TUMOR RECURRENCE AND TAMOXIFEN RESISTANCE: IS TAMOXIFEN RESISTANCE THE SAME PROBLEM?Typically, most patients with breast tumors that are estrogen and progesterone receptor positive will respond to tamoxifen. When they develop resistance to tamoxifen after six months to a year of therapy, the tumor will begin to recur. Fortunately, for many patients who no longer respond to tamoxifen therapy another effective hormonal agent can be found. These alternative agents usually work for a period of time not exceeding a year, after which the patient again develops resistance. Tamoxifen tends to be given as a “first-line” therapy because it has significantly fewer side effects than other hormonal agents, so the development of resistance to this drug is a significant clinical problem.At one time it was thought that a patient who no longer responded to tamoxifen probably was not taking the drug as directed (thus not enough drug was getting into the breast tumor cells) or perhaps was eating a diet high in “phytoestrogens.” These are estrogenic compounds found in many plant products that were believed to stimulate the growth of breast cancer cells just as estrogen does. The phytoestrogens are known to be capable of diminishing the effects of the antiestrogen tamoxifen. Weight gain over a prolonged period was also suspected to contribute to the loss of tamoxifen effectiveness. Because tamoxifen is a drug that is taken up by the fat cells and often retained in fatty tissue, an increase in weight without an increase in tamoxifen dose was believed to decrease the amount of drug available to the breast tumor. Even though all these explanations are plausible, their overall contribution to tamoxifen resistance is now considered minimal. Tamoxifen resistance apparently is associated with resistant mechanisms at the level of the breast cancer cell itself.*42\320\2*