Is There a Fourth Type of Diabetes?

by Shannon Dubois

We all know about diabetes: the infamous enemy of our bodies’ blood glucose homeostasis; the delicate balancing act between insulin and glucagon to keep our blood sugar stable. Type 1 and type 2 diabetes are the most well-known and talked about, type 3 was brought to the table a few years ago, and type 4 has just been “discovered.” So, what is this newest type of diabetes, and should we be worried?

As a reminder, type 1 diabetes is the insulin-dependent form of diabetes mellitus where pancreatic beta cells (typically destroyed by an autoimmune response) do not supply insulin to the body to signal cellular glucose uptake, resulting in high blood sugar.

Type 2 diabetes mellitus is primarily caused by insulin resistance (cells becoming desensitized to insulin’s action due to overuse), and decreased insulin production over time as the pancreas gets “worn out” from overproduction. This type of diabetes is often associated with obesity, inactivity, and aging.

The less talked about, newly termed (by some) type 3 diabetes is discussed in a 2008 literature review and is proposed to be linked to insulin deficiency and insulin resistance in the brain as contributors to Alzheimer’s Disease neurodegeneration, thus a sort of combination of type 1 and 2 that can lead to cognitive decline.

Now to the latest discovery: a fourth type of diabetes to keep on our radar. An article published around mid-November in Nature detailed the results of a study led by Salk Institute researchers who were investigating age-associated insulin resistance. They discuss how obesity-associated insulin resistance (driven by inflammation due to macrophages), which is deemed to be a large contributor to type 2 diabetes, is different from age-associated insulin resistance, which occurs independent of obesity.

The authors explain that “fat-resident regulatory T cells, termed fTreg cells, accumulate in adipose tissue as a function of age, but not obesity.” These cells lead to the age-associated insulin resistance that the article discusses. Thus, it seems that no one is safe from this disease—even the lean and physically active healthy eaters can fall prey to type 4 diabetes as a simple consequence of aging.

The article concludes that fTreg cells are implicated as potential therapeutic targets for treating age-associated insulin resistance, suggesting that fTreg cells could be depleted to increase insulin sensitivity and, therefore, ameliorate diabetes symptoms.

Overall, it doesn’t seem that this is a newly discovered type of diabetes per se, because it has long been known that even lean people are sometimes diagnosed with diabetes. Whether it was believed to be due to a genetic predisposition, or just attributed to the process of aging, it seems that this article is more the discovery of a mechanism that may be at play than of the condition itself.

The authors suggest “type 4 diabetes as a designation for non-obese-dependent fTreg-driven metabolic disease of the elderly,” and this may be an appropriate designation for the mice they have studied, but maybe not to classify humans just yet. This study did only include mice, so their findings would have to be proven in humans as a next step. Keep an eye out for future research on this topic, as it is hopefully coming soon.

Shannon Dubois is a second-year Master’s student studying Biochemical and Molecular Nutrition.

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