Recently a large amount of evidence has linked type 2 diabetes with obesity. However, type 2 diabetes has also been closely associated with chronic systemic inflammation. As the review article by Kolb and Mandrup-Poulsen entitled "An Immune Origin of Type 2 Diabetes?" suggests, obesity (or a high calorie diet) is not enough to induce the insulin resistance that is characteristic of type 2 diabetes. In contrast, the research appears to indicate that several proinflammatory genes and infiltration of adipocytes by macrophages in response to inflammatory cytokines ultimately cause insulin resistance that results in type 2 diabetes. This evidence suggests that if an individual has obesity as well as a genetic predisposition (activated proinflammatory genes) then the infiltration of adipocytes by macrophages, insulin resistance, and type 2 diabetes would be likely to result.
In particular, cytokines such as TNF-α and IL-6 have been implicated in this process as they are produced by the activated macrophages. As the article states, disruption of genes for several TNF- α receptors can actually prevent insulin resistance in animal models. However, such drastic measures are obviously not desirable in humans. Moreover, the result of creating such a gene defect is likely to differ given different genetic backgrounds (i.e. humans and mice). There is also indication that IL-6 may also be beneficial in lowering blood glucose levels as a result of muscle-derived IL-6 released during exercise. This conflicting evidence for the role of IL-6 as a component of inflammation connected with type 2 diabetes helps to illustrate just how complicated this disorder is. Ultimately, the question becomes what method is best to treat this low-level inflammation in order to reduce the risk of developing insulin resistance. Is it really beneficial to treat patients with NSAIDS and other anti-inflammatory drugs? What are the long-term risks of suppressing or, at least, decreasing levels of inflammation within the body?
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ReplyDeleteI would think that long term use of anti-inflammatory drugs would hinder wound healing, cause gastrointestinal damage and may become a problem if the patient were ever to stop taking anti-inflammatories. The body would have adapted to the constant onslaught of anti-inflammatory drugs that it may overproduce inflammatory factors once that suppression is gone. Now that the age of people with diabetes is dropping, we might start to see people who take anti-inflammatory drugs for 40 years or more, which may turn out to be more harmful in the long run.
ReplyDeleteI think a short-term use of anti-inflammatory drugs are beneficial in treating patients' pain. However, a long-term suppressing of inflammation could lead to more complications in the body. The mechanism of inflammation is necessary for body to heal, protect, repair, and detoxify its tissues. Therefore, by suppressing inflammation the body would not be able to repair itself. In addition,in a long run anti-inflammatory drugs damage the liver. Despite all the negativities of anti-inflammatory drugs, if inflammation is left untreated, it would lead to cardiovascular diseases and cancer. Now the question is, is it worth to use anti-inflammatory drugs or use an alternative safer treatment if there is one?
ReplyDeleteI think for the most part over the counter NSAIDS (Ibuprofen) don't seem to cause significant immunosuppression. In fact, Ibuprofen is used to speed healing in athletes by decreasing muscle and joint inflammation. But if inhibiting COX-2 really does help prevent diabetes the benefits should outweigh the risks. Even better, a drug that inhibits the inappropriate up-regulation of COX-2 in systemic inflammation might be preferable. Indeed, the most concerning side effect of the NSAID family is the nasty stomach issues caused by inhibiting COX-1.
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