Acquired Organ Dysfunction

These refer to nongenetic defects in glucose homeostasis that occur as diabetes develops. This concept was first identified in studies that intensively treated glycemia in persons with type 2 diabetes, with resultant improvement in B-cell function (33). Later studies showed some reversal of insulin resistance. This effect is unrelated to the type of treatment used to lower the glucose level (34), and is most effective early in the disease. Studies have shown long-term recovery of glucose tolerance in newly diagnosed patients with type 2 diabetes after a short-term insulin infusion or high dose sulfonylurea therapy (35,36).

A particularly interesting study was performed in subjects with an average duration of 8 years of type 2 diabetes who were placed on an insulin pump for 3 weeks, attaining excellent glucose control (37). The pump was stopped, and the subjects studied 2 days later, at which time large improvements in B-cell function along with normalization of hepatic glucose production and some improvement in insulin resistance were seen. These three problems make up the classic triad of type 2 diabetes. A question posed at the beginning of this review is why patients invariably have this triad, when the organs involved lack a known physiological link. One answer is that, irrespective of the genetic and environmental factors in any given patient, as glucose intolerance develops the acquired organ abnormalities result in the "common phenotype" of the disease.

A substantial amount of research has focused on these acquired abnormalities, in particular B-cell dysfunction. It was initially assumed the reversal of ^-cell dysfunction noted above stemmed from the improvement in blood glucose level, and the term "glucose toxicity" was coined (38,39). Supporting that idea were studies showing that experimental hyperglycemiain rodents invariably caused similar B-cell dysfunction to that occurring in diabetic humans (40), which was reversed by a glucose-lowering agent called phlorizin that restores normoglycemia by lowering the threshold for glucose clearance into urine, thus promoting glycosuria (41). Many mechanisms for hyperglycemia-associated B-cell dysfunction have been described from in vitro cell systems and animal models, and will be discussed later.

Also discussed later is a more recent suggestion that relates to another component of the diabetes phenotype, high circulating levels of triglycerides and fatty acids, as a cause of acquired organ abnormalities: so-called "lipotoxicity" (42). There has also been interest in the combined effects of both elements, termed "glucolipotoxicity" (43,44).

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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