Diabetes isn't a blood sugar disease, but rather a beta cell dysfunction disease.
That's what a new collaborative report from top diabetes scientists and medical officers says. By couching it that way, we may no longer talk about just "having diabetes" or not, but rather being able to identify which development stage of diabetes one is in.
Experts believe that focusing on early stages will allow them to fine tune both treatments and cure research, with interventions before people develop full-blown type 1 or type 2 -- or even a host of subset types of diabetes that still need to be classified.
The new 39-page report, published in mid-December in tandem with the new 2017 Standards of Care released by the American Diabetes Association, represents years of research and collaboration by the ADA and JDRF, along with the American Association of Clinical Endocrinologists (AACE) and the European Association for the Study of Diabetes (EASD).
"I personally think this is a truly profound change," says Dr. Robert Ratner, who served as the ADA's Chief Scientific and Medical Officer up until his recent retirement at the end of the year. "We were able to bring old-school international groups together for a research consensus, and we were able to incorporate it into our ADA Standards of Care that are used internationally for guidance. In essence, what we’ve done is to define diabetes by something other than glucose, and it’s the first time that is the case."
In essence, the report details how various pathophysiological pathways lead to various subtypes of diabetes, above and beyond just abnormally high glucose.
Key Findings for Type 1
Significantly, the report highlights research on beta cell dysfunction in people developing type 1 diabetes, indicating that someone with two or more autoantibodies will develop hyperglycemia (high blood sugar) and that may represent full-blown T1D. By defining type 1 at this earlier-than-traditional point, researchers believe there's more potential to reduce DKA (diabetic ketoacidosis) instead of waiting for those dangerous symptoms to occur.
T1D early stages are defined as:
- Stage 1: Autoimmunity plus normal glucose tolerance
- Stage 2: Autoimmunity plus abnormal glucose tolerance (fasting BGs >100 mg/dL; random BG over 140; an elevated A1C of 5.7%+, or generally increasing A1C values)
- Stage 3: Classic symptomatic T1D requiring insulin therapy
A big goal here is to eliminate the "surprise factor" in a D-diagnosis that often leaves families -- especially kids and their parents -- reeling from sky-high glucose levels and dangerous DKA experiences. The same goes for adults, who are still often misdiagnosed by both general practitioners and endocrinologists who too-quickly toss out a type 2 diagnosis when it should have been T1D. With childhood obesity and insulin sensitivity rates rising, the JDRF sees this as the time for re-defining these early stages to help make it more clear what kind of diabetes someone may have or be on the path toward.
You may remember that JDRF was already hot on this topic a couple of years back, leading an effort under the heading of "Early Stages of Type 1." But now the conversation has broadened to include not only type 1, but also type 2 and how to address "prediabetes" in new and better ways. Apparently, the paths to beta cell dysfunction in type 2 are less known than in T1D at this time, and the report says "more classification schemes will be needed" to clarify that.
Nevertheless, this whole effort is an important milestone for the groups and researchers involved, who are taking a collective stand to make this new approach a reality.
Putting Prediabetes on the Map
Ratner tells us that in this report, type 2 and prediabetes are still pretty much lumped together. But there is a separate push within the research community -- and among Pharma itself -- to change the conversation on prediabetes.
Right now, the FDA doesn't even define prediabetes. As a result, there is no clearly defined way for researchers to study it or for manufacturers to develop medications that could treat it. Ratner and others hope that can change.
A coalition of the ADA, AACE, and the Endrocrine Society has approached FDA with a petition to get the baseline T2 oral drug metformin approved for the treatment of prediabetes, Ratner says. That is an uphill battle, he says, but the group is working hard to make this happen, and plans to have data available in early 2017 to go back to the agency for more detailed discussion.
The big goal of course is prevention of type 2.
As to what's next, Ratner hopes that on the T1D side both investigators and industry will start going to the FDA with clinical trial designs that identify individuals "at-risk for type 1 diabetes." If the agency accepts that pathway to approve drugs, it could lead to a new age of diabetes treatments and understanding. Simultaneously, Ratner hopes the FDA approves the petition for metformin in certain cases of prediabetes.
But despite all the focus on various types and subtypes, "we've come to the important conclusion that types of diabetes are more alike than they are different," Ratner says. "The natural history is different, but we've come out and said that with rare exceptions, all forms of diabetes are due to either the destruction or dysfunction of beta cells. That's why it is now in the Standards of Care, we're putting a stake in the ground, saying it's a beta cell disease and we need to preserve the function and mass."
From our POV, a new approach can never hurt -- given that the status quo in diabetes care leaves a lot to be desired. Bravo, scientists!