Is Type 2 Diabetes an Autoimmune Disease?Friday, April 22, 2011
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.
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