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Type-2 diabetes linked to an autoimmune reaction: here’s what you need to know

As providers, we know that type-1 diabetes is due to an autoimmune reaction where the body attacks the beta cells of the pancreas, but here’s something diabetes-related that most of us haven’t heard much about: Ongoing research suggests that the pathogenesis of type-2 diabetes may actually have its roots in an autoimmune reaction. In this article, I’ll share the details of this developing hypothesis, and I’ll share some ideas on how I believe this should influence our approach to treating type-2 diabetes.

Is type-2 diabetes actually an autoimmune disease? What does the research say?

Here’s the scoop on the research: We know that hyperglycemia, which is the most well-known symptom of diabetes, arises as a result of the body’s resistance to insulin. In the pre-clinical trial I’m referencing, researchers demonstrated that the insulin resistance may actually be a result of B cells and other immune cells attacking the body’s own tissues.[1] In other words, it may be due to an autoimmune reaction.

Here’s how the study authors’ research supported their hypothesis: The researchers fed two groups of mice a high-fat, high-calorie diet—one group consisted of regular mice (group 1) and the other group consisted of mice lacking B cells (group 2). They noted that B cells accumulated in the visceral adipose tissue of the mice in group 1 in response to the high-fat, high calorie diet. These obese mice subsequently developed insulin resistance and glucose intolerance. As the mice in group 2 lacked B cells, there was no influx of B cells in response to their dietary changes. Although the mice in group 2 gained weight, they did not develop insulin resistance or glucose intolerance.

The researchers then treated the mice in group 1 with an antibody that targets and eliminates mature B cells called anti-CD20. When treated with this antibody, the insulin resistance and glucose intolerance observed in the mice in group 1 normalized, suggesting that the influx of B cells contributed to the development of their symptoms.

Now, what exactly is anti-CD20? Interestingly, the human counterpart of the antibody anti-CD20 is sold as the drug rituximab (trade names: Rituxan and Mabthera). You may recognize this drug as a common treatment for various autoimmune disorders.

Why would an autoimmune drug lead to resolution of type-2 diabetes symptoms?

Based on this study and their previous research, the study authors explained that mice who are fed a high-fat, high-calorie diet begin to store the extra calories in their visceral adipose tissue. As the adipocytes begin to grow rapidly and as they outgrow their blood supply, they begin to die. This phenomenon is also seen in individuals diagnosed with type-2 diabetes. As the contents of the dying cells are released, macrophages are drawn to the area in order to phagocytose and clean up the remnants. This results in a massive immune reaction involving macrophages, B cells, and T cells, and a significant increase in inflammation. This immune reaction also leads to a decrease in insulin sensitivity as the hormone is less able to access and bind to receptors on the remaining adipocytes. Fatty acids are also released into the circulation, contributing to hyperlipidemia, hypertension, fatty liver disease, and increased insulin resistance.

How does this change how we should approach the treatment of type-2 diabetes?

This discovery opens the door to novel potential therapies for the treatment of type-2 diabetes. In fact, the researchers who conducted this study predicted that physicians will be switching their focus from hypoglycemic medication toward immune-modulating therapies for the treatment of type-2 diabetes in years to come. I agree with this assessment, as I’ve always incorporated immune-modulating therapies in my treatment plans for my patients who’ve been diagnosed with diabetes, and I’ve seen great results doing so in combination with insulin-sensitizing and hypoglycemic therapies. Although it typically takes over 10 years for a practice to progress from research to the standard of care, I’m hopeful that this change will occur much more rapidly.

In my practice, I take an integrative approach to addressing chronic disease, and I frequently incorporate botanical medicine as a treatment modality. Two of the immune-modulating botanicals that I’ve found to be beneficial with my diabetic patients are Reishi (Ganoderma lucidum) and Cordyceps (Cordyceps sinensis and C. militaris). [2] [3] I like to use these medicinal mushrooms when addressing diabetes because they’ve been demonstrated to have immune-modulating properties, but research demonstrates that they have hypoglycemic and adaptogenic properties as well, both of which are beneficial in the treatment of type-2 diabetes.

You can seek additional training and choose to incorporate botanical medicine into your practice, or you can begin doing something as simple as helping patients adopt an anti-inflammatory diet or helping them increase their consumption of omega-3 fatty acids relative to their omega-6 consumption. Regardless of how you choose to incorporate immune modulation and inflammation reduction into your diabetic patients’ treatment protocols, I believe it’s something that should be done, in light of emerging research.



[1] Winer, D. A., Winer, S., Shen, L., Wadia, P. P., Yantha, J., Paltser, G., Tsui, H., Wu, P., Davidson, M. G., Alonso, M. N., Leong, H. X., Glassford, A., Caimol, M., Kenkel, J. A., Tedder, T. F., McLaughlin, T., Miklos, D. B., Dosch, H. M., & Engleman, E. G. (2011). B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature medicine, 17(5), 610–617.

[2] Liu, Q., & Tie, L. (2019). Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Diabetes. Advances in experimental medicine and biology, 1182, 201–215.

[3] Cao, C., Yang, S., & Zhou, Z. (2020). The potential application of Cordyceps in metabolic-related disorders. Phytotherapy research : PTR, 34(2), 295–305.


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