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Therapeutic Implications Potentially Effective

As an adjunct to manipulating macronutrient ratios, potential benefits have been associated with the following non-pharmaceutical interventions as part of an overall, sound dietary approach to improve diabetes and endothelial dysfunction. These include but are not limited to: anti-oxidants200 such as vitamins E 97, 305-308 , and C, 112, 309-311 and alpha lipoic acid 312, 313 , coenzyme Q10 314, 315 , L-arginine 212-214 187, 316, 317 , magnesium 318-321 , folic acid 322-326 , 327 , gamma linolenic acid (GLA) 170, 172-174, 176, 328 , the omega 3 fatty acids, DHA and EPA, 104, 329-332 chromium picolinate, 333 334-336 vanadyl sulfate,235-239 and soluble fiber. 50, 51, 337-339

Is medical practice being unduly influenced?

Using a concentrated omega-3 preparation, Harris et al 340 recently demonstrated safety and efficacy in patients with marked hypertriglyceridemia. Plasma TG levels and LDL cholesterol were reduced by approximately 45 percent over a four-month period while HDL increased by 13 percent. Others have found similar results with fish oil supplements without deleterious effects in diabetics. A review of 26 trials of omega-3 rich fish oil and diabetes confirms fish oil has no adverse effects on blood glucose and effectively lowers triglycerides by almost 30 percent 104 .

The results of omega 3 studies are at least as good as, if not superior to, the best clinical drug trials, yet these and other highly effective non-drug therapies are underused primarily because they are unpatentable. Unlike new beta-blocker and statin agents, there is no economic incentive on the part of major drug companies (or governments) to bankroll physicians and support research, education, and marketing campaigns aimed at physicians and consumers. According to Scott-Levin, a Pennsylvania consulting firm, during the first eleven months of 1998 alone the pharmaceutical companies spent $5.3 billion sending representatives into U.S. doctors’ offices and hospitals, and an additional $1 billion holding marketing events for doctors. That translates into nearly one drug salesperson and almost $100,000 for every dozen practicing physicians in the United States 341 . This does not include the billions spent on research and development which helps subsidize physicians’ incomes. Let’s not pretend this is not influencing medical practices, policies, and focus. These have already led to an obsession with lowering cholesterol and blood glucose without enough attention paid to other important issues. These include the other components of lipid profiles (e.g. triglycerides, HDL, and LDL size) and the consequences of “improving” glycemia without improving (and possibly worsening) macrovascular disease and longevity. There already may be available more effective, less expensive treatments with fewer adverse effects.

Dietary approaches can modulate insulin production and eicosanoid balance thereby improving endothelial dysfunction, insulin resistance, and the most important clinical outcomes, CHD events and longevity. Considering intensive treatment of glycemia with insulin-raising therapies should be reserved until after implementation of the following modalities: lowering glycemic load to reduce insulin levels (or exogenous insulin requirements) by eating moderate amounts of carbohydrates from mostly low glycemic fruits and vegetables. Consuming adequate amounts of protein from mostly low-fat sources, and consuming adequate amounts of fat mostly from monounsaturated sources. Trans fats or partially hydrogenated oils must be avoided and attention must be paid to lowering the omega-6 to 3 PUFA ratio by encouraging the consumption of fish oil (the best source of DHA and EPA) and decreasing the consumption of vegetable oils. Olive oil is best for cooking. Flaxseed oil and other sources of ALA must be converted in the body to the essential fatty acids, EPA and DHA. This is an extremely inefficient process and some individuals totally lack this ability 342, 343 . Some commercial enterprises are offering DHA and EPA harvested from the algae and plankton sources that become incorporated into the flesh of the deep coldwater fish that ingest them. Unfortunately many of these fish today are raised in aquaculture farms without access to plankton and algae. These fish lack the essential omega 3 fatty acids, which is why supplements are necessary.

Conclusions
Clearly it is desirable to lower blood glucose but intensive control at the expense of raising insulin levels is not the answer and may be counterproductive. Perhaps the light should focus on improving the underlying problem of endothelial dysfunction and glycemic control through improved nutritional interventions rooted in sound science. The literature supports a number of lifestyle interventions including exercise, stress reduction, and diet. Reducing or controlling glycemic load is critical, supplying adequate protein, avoiding partially hydrogenated oils or trans fats, adding omega 3 fatty acids may also be beneficial, and providing meals in a convenient fashion may further add to the success of a dietary intervention program. A model has been presented re the pathophysiology of the insulin resistance syndrome and type 2 diabetes with nutrition and endothelial cell dysfunction at the core. Building on this model emerges a paradigm for improving insulin resistance and diabetes through the manipulation of macronutrients. Micronutrients such as antioxidants, magnesium, l-arginine, GLA, omega 3 fatty acids, and vanadyl sulfate can and may be incorporated into this model.

Diabetes (greater than 16 million) and metabolic syndrome (47 million) 344 together affect almost one in four Americans including children. Over two-thirds of all morbidity, mortality, and health care costs resulting from these epidemics are caused by macrovascular pathology—strokes, cardiovascular, and peripheral vascular disease. We have no intervention trial data clearly showing improvement in macrovascular outcomes with using drugs for glucose control, 345-347 and no drug can be considered completely without potential adverse effects. While I am not advocating the abrupt abandonment of all drugs, I am suggesting the consideration of lifestyle changes as a first line intervention.

The data suggest that the wrong diet can increase the risk of diabetes while the right diet and lifestyle can prevent and reverse it. Providing food has been shown to reduce CHD risk 200-202 and may be a useful strategy for promoting weight loss. 203 Eating smaller, more frequent meals spreads out the “nutrient load,” slows absorption of carbohydrates, helps stabilize insulin and glucose levels, 188 may prevent overproduction of free radicals, 112, 115, 189 and can lower total and LDL cholesterol and CHD risk. 190-192

Perhaps a solution to type 2 diabetes, CHD, and obesity is to conveniently provide patients with all of their meals—food that tastes great, satisfies, controls hunger, and is scientifically sound, i.e., devoid of trans fats, balanced and low or moderate in glycemic load, adequate in lean protein, featuring monounsaturated and omega 3 fatty acids, all combined in the form of calorie restricted meals (three meals and two snacks) to be eaten throughout the day. Consider diet before drugs. In seeking the best approach to diabetes and other diseases, maintain an open mind and consider all aspects not only the ones upon which the light shines brightest.

Eric S. Freedland, MD graduated from University of Rochester School of Medicine in 1982, trained in internal medicine at Mt. Auburn Hospital in Cambridge, MA, and emergency medicine at Harbor-UCLA Medical Center in Torrance, CA, and has held faculty positions at Harvard Medical School (1990-1991) and Boston University School of Medicine (1992-1997). Dr. Freedland has developed a nutrition-centered model of disease with a special emphasis on diabetes. A staunch advocate for prescribing lifestyle changes before drugs, Dr. Freedland has written and lectured extensively on this subject.

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