We are Here to Help Type 2 Diabetes

Newsletter Archive

Article by Dr. Sheri Colberg, Phd, FACSM

 

E-Commerce Solutions

 

INFLAMMATION, INSULIN RESISTANCE AND TYPE 2 DIABETES


  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • : Function ereg() is deprecated in /home/diabins/public_html/includes/file.inc on line 895.
  • strict warning: Only variables should be passed by reference in /home/diabins/public_html/sites/all/modules/autosave/autosave.module on line 63.

The medical profession is still evaluating the role of inflammation in the onset on type 2 diabetes. But the latest signs are that it could be a crucial factor in the disease which is reaching epidemic proportions throughout the world.

Inflammation is part of the body's immune system, which triggers a defense response to harmful stimuli. The body reacts to injury by sending specialized blood cells to damaged areas where they attack "invaders" like the renegade molecules called "free radicals" and clean up dead and dying cells.

Blood Glucose Monitor.In the case of inflammation and diabetes, the "invader" is thought to be excess levels of insulin, which can be caused by the imbalance of blood glucose and insulin called Insulin Resistance.

Inflammation can take an external form like the reddened, tender skin which draws attention to a splinter in your finger. Or it can be an unseen, internal process in response to something harmful like high blood pressure.

To combat internal harm, inflammation produces C-reactive protein (CRP), which, unfortunately, can damage the arteries by helping to form plaque while attempting to tackle a long-term condition like high blood pressure.

Plaque is a substance that attaches itself to artery walls, damaging those walls and seriously impairing blood flow, which can leading to a heart attack or stroke. A blood test measures CRP levels and the higher that level is, the more at risk you are from cardiovascular disease. There's contradictory evidence about whether CRP levels and Insulin Resistance are closely linked.

Research about inflammation is often cutting edge material that still needs ample verification. But scientists are gathering data that inflammation precedes and predicts type 2 diabetes. Previous research had already linked inflammation to heart disease and obesity, which are both common in people with diabetes.

Type 2 diabetes is characterized by high blood-sugar concentrations that result from defects in the body's use or production of insulin. Normally, insulin guides sugar, the body's basic fuel, from the bloodstream into cells. Unbalanced insulin levels, which can be caused by Insulin Resistance, lead to unhealthily high concentrations of blood sugar can lead to heart disease, blindness, kidney disease and circulation problems that may require amputations.

Scientists on the frontier of diabetes research are testing people's blood samples not only for insulin and glucose levels but also for a variety of compounds associated with inflammation. Some of these, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), are cytokines-chemical signals that the immune system uses to marshal inflammatory activity.

Others, such as so-called acute-phase proteins made by the liver, rise in response to increased cytokine concentrations. These proteins don't contribute directly to inflammation but, because they remain detectable in blood longer than cytokines do, they are a convenient measure of it.

Microscopic view of fibers.The concentrations of cytokines and acute-phase proteins, such as C-reactive protein (CRP) rise at least a hundredfold when a person contracts an infection. By contrast, in most studies linking inflammation to diabetes and to heart disease, these inflammation markers reach only perhaps twice-normal amounts. So it's not clear whether at such low concentrations the cytokines trigger swelling or other inflammatory responses.

Although analyses of different indicators of inflammation sometimes produce conflicting findings, evidence is piling up that what the researchers call low-grade inflammation does indicate an increased risk for type 2 diabetes. It also seems to boost the likelihood of Insulin Resistance playing a key role in diabetes, which often precedes the latter disease.

Most of the evidence comes from analyses of blood samples and data collected in studies that have followed the health of large numbers of people over several years. All these investigations have used statistical techniques to take into account various factors, such as obesity, that might confound their results.

Recent support for the CRP-Diabetes link came from a study presented in the October 2001 edition of Diabetes journal. Researchers tracked 5,888 U.S. residents without diabetes, 65 or older, who got their health care from the Kaiser Permanente health maintenance organization. Among the quarter of people with the highest CRP blood concentrations at the beginning of the study, twice as many had been diagnosed with diabetes after 3 to 4 years, compared with the quarter of people with the lowest CRP concentrations.

Other researchers have looked at both CRP and cytokines. As part of a long-running national study, researchers at Brigham and Women's Hospital in Boston compared the medical histories of 188 middle-aged women who had diabetes with records on 362 women of similar age and weight who didn't. The quarter of women who had the highest CRP concentrations early in the study were four times as likely to develop diabetes as the 25 percent of women with the lowest CRP concentrations.

Grandmother and Granddaughter.Also, women with the highest IL-6 concentrations were more than twice as likely to develop diabetes as the women with the lowest IL-6 concentrations. Finally, those with the highest concentrations of both IL-6 and CRP were six times as likely to develop the disease over the course of the study as women with low concentrations of the two compounds.

An international study of originally non-Diabetic men and women has also suggested that "something is going on" between inflammation and type 2 diabetes.

During long-term tracking of 10,397 people in Brazil, 651 developed type 2 diabetes. Comparing that group with 643 age- and weight-matched people in the study who remained free of the disease, researchers found that high concentrations of CRP didn't predict diabetes risk. But people with the highest concentrations of sialic acid, a measure of CRP and several other acute-phase proteins, were 70% more likely to develop diabetes than those with the lowest concentrations.

None of these epidemiological studies can prove that inflammation causes diabetes, however, and it's possible that some unknown factor pre-disposes people to both conditions. One candidate is obesity. Fat cells are known to produce cytokines, with CRP typically elevated in people who are overweight.

Some studies suggest inflammation causes Insulin Resistance. Animals with infections and those with cancer naturally have high concentrations of cytokines, with scientists detecting increased Insulin Resistance in these animals.

Researchers are now examining whether animals without underlying disease but with altered amounts of inflammatory cytokines are vulnerable to diabetes. For instance, mice lacking the gene for the cytokine TNF-alpha are less likely to develop obesity-linked Insulin Resistance than are mice with that gene. Recently scientists have shown that TNF-alpha blocks insulin from getting into cells.

The medical jury is still out on all these matters. But the general picture is likely to become clearer in the not-too-distant future.

References:

Abdella, N.A., et al. 2002. Case control study of C-reactive protein with coronary heart disease in patients with type 2 diabetes mellitus (Abstract 669-P). 62nd Scientific Sessions of the American Diabetes Association. June 15. San Francisco.

Aljada, A. . . . and P. Dandona. 2002. Glucose intake induces an increase in AP-1 and Egr-1 in mononuclear cells and plasma matrix metalloproteinases and tissue factor concentrations (Abstract 987-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Barzilay, J. 2002. Inflammation: Cause or consequence of diabetes mellitus? American Diabetes Association. June 16.

Dandona, P., et al. 2002. Acute hyperglycemia increases the reactive oxygen species (ROS) generation by mononuclear cells (MNC) and impair the brain artery reactivity in healthy volunteers (Abstract 1283-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Duncan, B.B., et al. 2002. Acute phase reactants, interleukin-6 and the development of diabetes mellitus? The ARIC Study (Abstract 117-OR). 62nd Scientific Sessions of the American Diabetes Association. June 15. San Francisco.

Festa, A., et al. 2002. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: The insulin resistance atherosclerosis study. Diabetes 51(April):1131-1137. Abstract available at http://diabetes.diabetesjournals.org/cgi/content/abstract/51/4/1131.

Ghanim, H. . . . and P. Dandona. 2002. Troglitazone suppresses pro-inflammatory transcription factors, early growth response (Egr-1) and activator protein-1 (AP-1) in mononuclear cells: Further evidence of the anti-inflammatory effects of troglitazone (Abstract 396-P). 62nd Scientific Sessions of the American Diabetes Association. June 15. San Francisco.

Hundal, R.S. . . . S.E. Shoelson, et al. 2002. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. Journal of Clinical Investigation 109(May):1321-1326. Abstract available at http://www.jci.org/cgi/content/abstract/109/10/1321.

Kirwan, J.P., et al. 2002. TNF-a is a predictor of insulin resistance in human pregnancy. Diabetes 51(July):2207-2213. Abstract available at http://diabetes.diabetesjournals.org/cgi/content/abstract/51/7/2207.

Mohanty, P. . . . P. Dandona. 2002. Evidence for a potent anti-inflammatory effect of rosiglitazone in obese diabetes patients (Abstract 441-P). 62nd Scientific Sessions of the American Diabetes Association. June 15. San Francisco.

Möhlig, M. . . . H. Boeing, et al. 2002. Interleukin 1 beta (IL-1b) is a permissive factor for development of type 2 diabetes mellitus (T2DM) (Abstract 118-OR). 62nd Scientific Sessions of the American Diabetes Association. June 15. San Francisco.

Senn, J.J. . . . and R.A. Mooney. 2002. Suppressor of cytokine signaling-3 (SOCS-3) is a potential mediator of interleukin-6 dependent insulin resistance (Abstract 1323-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Senn, J.J. . . . and R.A. Mooney. 2002. Interleukin-6 inhibits insulin receptor signaling transduction in hepatocytes (Abstract 1235-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Tripathy, D. . . . and P. Dandona. 2002. Acute elevation of plasma free fatty acids increases reactive oxygen species (ROS) generation by polymorphonuclear cells, induces nuclear factor-kB (NF-kB) and impairs brachial artery reactivity in healthy subjects (Abstract 1299-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Yee, A. . . . and J.A. Johnson. 2002. Statins delay starting insulin in patients with type 2 diabetes mellitus (Abstract 982-P). 62nd Scientific Sessions of the American Diabetes Association. June 16. San Francisco.

Further Readings:

2002. International research links inflammation and type 2 diabetes. American Diabetes Association press release. June 16.

Barzilay, J.I., et al. 2001. The relation of markers of inflammation to the development of glucose disorders in the elderly. Diabetes 50(October):2384-2389. Abstract available at http://diabetes.diabetesjournals.org/cgi/content/abstract/50/10/2384.

Birnbaum, M.J. 2001. Turning down insulin signaling. Journal of Clinical Investigation 108(September):655-659.

Christensen, D. 2001. Inflammation linked to diabetes. Science News 160(Aug. 11):89.

Crook, M.A., P. Tutt, and J.C. Pickup. 1993. Elevated serum sialic acid concentration in NIDDM and its relationship to blood pressure and retinopathy. Diabetes Care 16(January):57-60. Abstract available at http://care.diabetesjournals.org/cgi/content/abstract/16/1/57.

Eckel, R.H., W.W. Barouch, and A.G. Ershow. 2002. Report of the National Heart, Lung, and Blood Institute--National Institute of Diabetes and Digestive and Kidney Diseases working group on the pathophysiology of obesity-associated cardiovascular disease. Circulation 105(June 18):2923-2928.

Fackelmann, K. 1997. Harbinger of a heart attack. Science News 151(June 14):374-375. Available at http://www.sciencenews.org/sn_arc97/6_14_97/bob1.htm.

Festa, A., et al. 2000. Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102(July 4):42-47. Abstract available at http://circ.ahajournals.org/cgi/content/abstract/102/1/42.

Freeman, D.J., et al. 2001. Pravastatin and the development of diabetes mellitus: Evidence for a protective treatment effect in the west of Scotland Coronary Prevention Study. Circulation 103(Jan. 23):357-362. Abstract available at http://circ.ahajournals.org/cgi/content/abstract/103/3/357.

Haffner, S.M. 2001. Do interventions to reduce coronary heart disease reduce the incidence of type 2 diabetes: A possible role for inflammatory factors. Circulation 103(Jan. 23):346-347.

Hotamisligil, G.S., et al. 1994. Tumor necrosis factor a inhibits signaling from the insulin receptor. Proceedings of the National Academy of Sciences 91(May 24):4854-4858. Abstract available at http://www.pnas.org/cgi/content/abstract/91/11/4854.

Mooney, R.A., et al. 2001. Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. Journal of Biological Chemistry 276(July 13):25889-25893. Abstract available at http://www.jbc.org/cgi/content/abstract/276/28/25889.

Pradhan, A.D. . . . and P.M. Ridker. 2001. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Journal of the American Medical Association 286(July 18):327-334. Abstract available at http://jama.ama-assn.org/issues/v286n3/abs/joc10096.html.

Seppa, N. 2002. Cardiac culprit: Autopsies implicate C-reactive protein in fatal heart attacks. Science News 161(April 20):244-245.

Travis, J. 2001. Insulin lowers more than blood sugar. Science News 160(Sept. 1):143.

Yuan, M., S.E. Shoelson, et al. 2001. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkb. Science 293(Aug. 31):1673-1677. Abstract available at http://www.sciencemag.org/cgi/content/abstract/293/5535/1673.

 

 

"I have been using the Insulite System for about 6 months. I have noticed that my eating habits seem to have transitioned very naturally.... no starvation or denial, I don't crave junk food or sweets anymore!! I have been able to lose about 20 pounds, slowly, safely, and permanently. This is a "for life" program and everyone that has a weight problem should try it!!"
Kat Healy
  Jamestown, VA
"Although I have never met any of your staff I feel that I get more positive response from you all than my doctors for the last five years.

I'm just so grateful for your organization. You have given me so much hope and something to look forward to. I feel as if I'm dealing with professionals who care about what happens to their patient."

Daniella McKnight
  England
 
 
"I cannot believe the difference the Insulite System has made in how I feel. My appetite has changed tremendously. I do not crave carbs and sugar and my appetite is somewhat diminished."
PR
  Bakersfield, CA

Insulin Resistance Articles

"I feel that the Insulite System has been helpful in pushing my daughter so much closer to normal. I've also seen less bottoming-out energy wise and more stable mood….."
A.E.
  Warren, NJ
"I think your site has the most helpful information of any of the diabetes-related sites. The information is very intriguing."
Dr. MJ Lewis
  Ewa Beach, HI

Insulin Resistance Articles

"I have been using the Insulite System for about 6 months. I have noticed that my eating habits seem to have transitioned very naturally.... no starvation or denial, I don't crave junk food or sweets anymore!! I have been able to lose about 20 pounds, slowly, safely, and permanently. This is a "for life" program..."
Kat Healy
  Jamestown, VA
"I have been on the Insulite System for approx 3 months. I have lost 33 lbs, my liver functions are normal and my A1C came back at 5.1, down from 8.03 months ago. I was taking 10 Glucovance pills daily, now I take only 2 pills in the AM. My blood sugar is normal, my energy is higher than it has been in years and I feel great. Insulite along with a change in my diet has changed my life.

I tell everyone that asks me what I have done to change my life, about the Insulite program. Your product is fantastic. I have cut out all sweets, flour, dairy and have no cravings."

Marta Garcia
  Santa Ana, CA
"In less than 3 weeks I've started losing weight again after being "stuck" on Weight Watchers for about a year. I've lost about 4 lbs since starting Insulite but more significantly my blood pressure is well within normal limits now and I can tell my metabolism is better. I am not getting that slump between meals and am able to control between-meal snacking, and I have a lot of energy throughout the day rather than periods where I need to nap. I just ordered the 6 months supply. Thank you!"
Teresa Ruth
  Boise, Idaho