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Is Type 2 Diabetes an Autoimmune Disease?



Insulin resistance is commonly observed in individuals with excess weight and has been considered a key mechanism underlying the rather strong association between obesity and increased risk for type 2 diabetes.

However, the etiology of insulin resistance associated with weight gain or why this develops in some people and not in others remains unclear.

As study by Daniel Winer and colleagues from the University of Toronto and Stanford University, just published in NATURE MEDICINE, now suggests a novel role of B-lymphocytes and autoantibodies in this relationship.

B lymphocytes are immune cells that recognise antigens and ultimately lead to the production of anti-bodies.

In this paper, the researchers show that B cells accumulate in the visceral fat of obese mice and that mice, lacking B cells appear protected against the development of insulin resistance with weight gain.

The paper further shows that the B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies.

Treatment of these insulin-resistant obese mice with a B cell-depleting CD20 antibody attenuates disease, whereas transfer of IgG from obese mice rapidly induces insulin resistance and glucose intolerance.

Most importantly perhaps, the researchers also show that insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies.

Not only do these studies suggest a novel role for B cells and autoantibodies in the development of insulin resistance associated with weight gain, but if confirmed, these findings could lead to novel diagnostic tools (early detection of antibodies) and perhaps new treatments for type 2 diabetes (anti-CD20 antibodies are already used to treat some autoimmune diseases and cancers in humans).

Differences (genetic or otherwise) in immune response may also explain why weight gain leads to insulin resistance and diabetes in some people but not in others (see previous post on insulin-sensitive obesity).

Certainly, if anything, this study can only remind us of the biological complexity of obesity – anyone who still believes obesity and its complications are simply a matter of calories in and calories out probably also believes that health can be easily measured in pounds or kilograms.

AMS
Edmonton, Alberta

Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, & Engleman EG (2011). B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature medicine PMID: 21499269

4 Comments

  1. Dr. Sharma, I have been reading about a possible autoimmune cause for type 2 diabetes. My brother has rheumatoid arthritis and is a type 2, with peak blood sugar at diagnosis in the mid 300s. He had peripheral neuropathy and has since resolved that through exercise and Metformin (I am sorry to say his diet is still kind of crappy). I tested free of detectable autoimmune issues (I had iritis and they couldn’t figure out why; it has not recurred) but I am insulin resistant, with a peak blood sugar at diagnosis in the 170s. I now keep my fasting blood sugar around 100-110 with Metformin. My brother and I have long suspected that we have different causes for our sugar issues. He believes his is related to his autoimmune disorder. I found a study on insulin resistance (http://www.ncbi.nlm.nih.gov/pubmed/21196154) that argues that it is caused by or associated with damage to the hypothalamus. It’s probably not inconceivable that autoimmune disorders damage the hypothalamus, but the hypothalamus is the main source of the response to stress. I’ve had enormous stress throughout my life and I have had significant anxiety for years. What do you think about the idea that metabolic syndrome, insulin resistance, type 2 diabetes, and other things of that type might have more than one unrelated cause? All I see online is people barking up this tree or that, without considering that they might in fact be chasing things up more than one tree! 🙂

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  2. I believe that T2DM is autoimmune and genetic. The media however as much as dances around this issue, there’s nothing definitive, just a few theories here & there. Mostly it’s a blame game; T2D patients are blamed for eating themselves to it an so forth. The fact that both athletic and skinny people can get it, too, is largely ignored. This sounds almost politically correct if you ask me.

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  3. Interesting article. The commonly held understanding suggests that Type 1 diabetes is caused by autoimmune reasons whereas Type 2 is not, and is a result of insulin resistance. Autoimmune disease mechanism is complex for most people to understand. Would like to share link to an infographic that makes it easier to understand for just about anyone.

    Autoimmune Diseases

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  4. Type 2 diabetes is in the process of being redefined as an autoimmune disease rather than just a metabolic disorder, said an author of a new study published in Nature Medicine this week, the findings of which may lead to new diabetes treatments that target the immune system instead of trying to control blood sugar.

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