What is inflammation?

Everyone is familiar with inflammation when it occurs at the skin: the skin becomes red, warm, swollen, and tender. But inflammation occurs internally also, and is a complex biologic response to harmful stimuli. This response involves the immune system as well as cells and other constituents within the blood, and causes different diseases depending on which organs of the body are attacked by the harmful stimulus. Inflammation is part of arthritis and other autoimmune disorders, inflammatory bowel disease, nephritis (inflammatory kidney disorders), atherosclerosis (hardening of the arteries), and diabetes.

The defining characteristic of type 1 diabetes is the chronic inflammation and destruction of the pancreatic beta cells due to autoimmune activation. It is also thought that the development of type 2 diabetes may be due to low-grade systemic inflammation and subsequent activation of immune processes in response to harmful stimuli.

Diabetes is a pro-inflammatory state

It is said that diabetes is a "pro-inflammatory state." That is, people with diabetes frequently have elevated levels of lab tests that are associated with inflammation ("inflammatory markers"). Reducing glucose levels with some diabetes medications (but not all) is associated with decreasing levels of these inflammatory markers. Metformin and insulin were found to have little effect (1), but rosiglitazone reduces inflammatory markers.

What are inflammatory markers?

Blood tests have been developed that indicate the presence of inflammation. Many such inflammatory markers have been identified, including WBC count, fibrinogen, C-reactive protein (CRP), and cytokines, chemokines, adhesion molecules, and others. Only some of these blood tests (such as fibrinogen, CRP, and WBC count) are currently available in medical laboratories, while other markers are useful in research settings only.

In addition to diabetes, many other medical and lifestyle conditions including rheumatoid arthritis, smoking, sedentary lifestyle, excessive alcohol consumption, and abdominal obesity are associated with high levels of inflammatory markers.

As mentioned above, reducing glucose levels with some diabetes medications (but not all) is associated with decreasing levels of these markers.

Can inflammatory markers be helpful in prediction of medical disorders?

Probably the most promising of the predictive inflammatory markers is hs-CRP (high-sensitivity C-reactive protein) (2), which seems to be a marker that may predict cardiac events in patients with coronary heart disease (3).

Can drugs that decrease inflammation help control diabetes?

It is well known that hyperglycemia contributes to vascular complications of diabetes. There has been considerable research into the interactions of inflammation and blood glucose levels, and high glucose has been shown to induce the release of markers of inflammation, both in experimental systems and in patients.

High-dose aspirin results in improvement of insulin sensitivity in people with type 2 diabetes (4). Treatment of type 2 diabetes with a drug for rheumatoid arthritis (anakinra) was shown to improve A1c (5). Studies of other anti-inflammatory drugs such as salsalate (6) are underway to see if they have a positive effect on glucose control and inflammation in people with diabetes.

To date, no drug that targets inflammation has been approved for use in control of hyperglycemia.

Also see

(1) Effects of Initiating Insulin and Metformin on Glycemic Control and Inflammatory Biomarkers Among Patients With Type 2 Diabetes, The LANCET Randomized Trial. JAMA. 2009;302(11):1186-1194.
http://jama.ama-assn.org/cgi/content/abstract/302/11/1186

(2) hs-CRP at Lab Tests Online
http://www.labtestsonline.org/understanding/analytes/hscrp/test.html

(3) Markers of Inflammation and Cardiovascular Disease. Circulation. 2003;107:499-511.
http://circ.ahajournals.org/cgi/content/full/107/3/499

(4) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest. 2002 May;109(10):1321-6.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150979/

(5) Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007 Apr 12;356(15):1517-26.
http://www.ncbi.nlm.nih.gov/pubmed/17429083

(6) Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D)
http://clinicaltrials.gov/ct2/show/NCT00392678