Fighting Progression of Type 2 Diabetes: Beta Cell Is Key

Steven E. Kahn, MBChB


September 23, 2016

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It's great, as usual, to be at the European Association for the Study of Diabetes Annual Meeting. A great amount of discussion is going on about the role of the beta cell in the pathogenesis of type 2 diabetes and how we are going to work to prevent the progressive loss of beta-cell function and mass that characterizes the disease.

It's clear that everybody recognizes that the beta cell is the key feature of why we get hyperglycemia as well as why we see a progression of the disease. With the approaches we are currently using, this disease results in a progressive loss of the ability of the beta cell to secrete insulin, along with loss of the beta cells that are responsible for making this critical hormone.

We've used many, many different approaches until now to try to prevent this loss of beta-cell function. We have a variety of classes of agents that have addressed the beta cell directly as well as indirectly, perhaps by reducing the load of the beta cell so that the demand for it to produce and secrete insulin is decreased.

What we've learned through a lot of these interventions is that although we can maintain glycemic control for a period of time, inevitably there will be progression and we will need to add agents.

Every patient with type 2 diabetes has beta-cell dysfunction, and every patient with type 2 diabetes needs to be aggressively treated to slow progression.

The different agents that we've used seem to have variable degrees of ability to slow progression. For example, the sulfonylureas, while being capable of stimulating insulin secretion, seem to drive the beta cell towards that inevitable loss of function far more rapidly than other approaches such as metformin or the thiazolidinediones.

In fact, if an individual were to live long enough, every patient with type 2 diabetes will have ultimate beta-cell failure that requires insulin-replacement therapy. We are losing patients to cardiovascular disease even with the more aggressive control of blood pressure and lipids, many of them before they've progressed to beta-cell failure.

The challenge is to come up with new approaches that would allow us to slow this progression. The traditional thinking, where one provides agents that stimulate the cell to secrete insulin, may not be optimal. We may need to start thinking of new approaches that would allow the beta cell to rest some and, therefore, be able to live longer.

Studies looking at individuals with prediabetes have identified that the beta cell is already defective.[1] With interventions that improve insulin sensitivity, we can typically slow the progression to diabetes. Similarly, if we intervene in individuals with diabetes to reduce the demand on the beta cells with approaches as simple as aggressive lifestyle changes, we can slow progression.

We need to clearly focus on these areas to try to prevent our patients from getting progressive hyperglycemia due to progressive beta-cell loss and, ultimately, the diabetic complications that we traditionally see with the disease.

We've been seeing recently that a number of the agents that are used to treat type 2 diabetes, including GLP-1 receptor agonists and SGLT2 inhibitors, may offer hope in reducing diabetic complications in individuals with very advanced disease. Although this is very useful information, we have yet to fully understand how this is happening. The challenge for all of us is to find approaches that can be used earlier in the disease, perhaps with these classes of agents or others that would not allow us to worry about late-stage disease.

In my mind, the beta cell is the key. We're going to have to aggressively target it. We don't necessarily have to target it by stimulating it as much as resting it.

Every patient with type 2 diabetes has beta-cell dysfunction, and every patient with type 2 diabetes needs to be aggressively treated to slow progression. Failure to treat our patients aggressively is going to allow accelerated progression and ultimately result in failure and insulin therapy.

In association with the Endocrine Society


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