Anti-inflammatories- a new cure for Type II Diabetes?

Type II Diabetes, a disease which has been increasing in prevalence throughout the modern world, is generally linked to obesity and an unhealthy diet. People with type II diabetes are able to produce insulin, unlike those who have type I diabetes, however, the insulin secreted by those with type II diabetes is either not enough to work properly, or their body is unable to recognize the insulin produced.  According to the review article assigned to this weeks class, type II diabetes is an autoinflammatory disease, in which the body is in a chronic state of inflammation in which interleukin-1 beta is produced and kills the beta islet cells in the pancreas (Dinarello). High levels of glucose can stimulate interleukin-1 beta production by the beta islet itself, and it can also be produced by fat cells (Dinarello). Therefore, anti-inflammatories such as interleukin-1 beta receptor antagonists can be beneficial in the treatment of type II diabetes by reducing interleukin-1 beta mediated inflammation. This is emphasized in the article "Anakinra Provides Sustainable Benefits for Diabetes," in which a study done by Dr. Thomas Mandrup-Poulsen from the Hagedorn Research Institute and Steno Diabetes Center in Gentofte, Denmark, is highlighted. Anakinra is an interleukin-1 receptor antagonist.

In Dr. Mandrup-Poulsen's study, over 70 patients were randomized to obtain Anikinra or placebo treatment for 13 weeks, adding on to their current diabetic therapy. He states that those who received 13 weeks of Anikinra treatment showed improvements in beta cell function, hemoglobin A1c levels (reflects blood glucose level), and systemic inflammation. Out of the 70 randomized patients, over 64 remained in the study to participate in the 39 week follow-up period. However, the author does not state what the criteria was to remain involved in the study, nor the reason as to why not all 70 of the patients were included in the follow up period. The authors state that at the end of the 13 week lead in period, there had not been a difference between anakinra treated patients and placebo treatment patients in A1c reduction, insulin sensitivity, or increase in insulin or metformin dose. However, during the 39 week follow up period of which none of the patients were administered Anakinra, the proinsulin/insulin ration remained significantly lower in the former Anakinra treated patients as opposed to then former placebo-treated patients. Similar results were expressed of the C-reactive protein and IL-6 levels, another cytokine which is involved in inflammation. Also, "previous responders had maintained their improved beta cell function and had achieved their target hemoglobic A1c levels with significantly lower increases in thier insulin doses, compared to the anakinra-unresponsive patients" (Diabetes Care).

Dr. Mandrup-Poulsen believes that the results of this study prove that type II diabetes is due to interluekin-1 beta mediated inflammation, and  that a  "short course of IL-1 blockade could be envisaged as add on to existing antidiabetic therapy to break the vicous cycle of glucose unduced IL-1 and IL-1 autoinduction in beta-cells" (Mandrup-Poulsen). 

However, there is another anti-inflammatory that is believed to have a positive effect on type II diabetes. Salsalate is an anti-inflammatory drug derived from salicylate and is primarily used to treat arthritis.  In the article, "Salsalate May Help Treat Type II Diabetes," it is stated that salsalate helps reduce blood sugar levels and helped with glycemic control within a variety of doses in people with type II diabetes. "In a study, published in the Annals of Internal Medicine, researchers randomly assigned 108 people with type 2 diabetes to receive 3, 3.5, or 4 grams per day of salsalate or a placebo in addition to their current diabetes therapy for 14 weeks" (Warner). The results showed that those who underwent salsalate therapy showed improvements of their blood sugar A1c levels, as well as other markers of glycemic control and heart disease risk (Warner). However, there were elevated levels of protein in the urine of some patients, which may indicate negative effects on the kidney. The author states that due to these negative effects and the small study sample, salsalate cannot yet be recommended as a treatment for type II diabetes.

In both articles, it is claimed that the pathogenesis of inflammation is involved in the onset of type II diabetes. Therefore, it is positively suggested by both studies that anti-inflammatories can potentially be used as treatment of type II diabetes once further research is enacted. What I disliked about the first article about the interleukin-1 beta blocker is that not a single negative side effect of the study was mentioned, nor was an explanation given as to why only 64 out of the 70 patients were allowed to continue to the follow up period. However, the fact that the study has moved onto a phase II trial is promising. 

What do you guys think about the pathogenesis of inflammation in type II diabetes and anti-inflammatory treatment for the disease?

Sources:

"Diabetes Care." Diabetes Care. 32. (2009): 1663-1668. Web. 25 Nov. 2012. <http://www.diabetesincontrol.com/studies/8400-&action=1>.

Dinarello, Charles A. "Leading Edge Review." Leading Edge Review. (2010): 939. Web. 25 Nov. 2012.

Warner, Jennifer. "WebMD HealthNews." WebMD HealthNews. (2010): n. page. Web. 25 Nov. 2012. <http://diabetes.webmd.com/news/20100315/salsalate-may-help-treat-type-2-diabetes>.