Results of the seven-year-long TODAY study (Treatment Options for Type 2 Diabetes in Adolescents and Youth) are out and as expected, they aren't pretty.
Bottom line of this study, which is the largest of its kind to ever be done: No matter what medication's being used, kids and teens have a harder time managing their type 2 diabetes and keeping blood sugars down. Lifestyle interventions and medications aren't working even when they're taken as prescribed, and racial differences are more important than we may have thought.
And the number of people joining this part of the D-community keeps on rising... Yikes!
For the last few years, we've been reading a lot about the increase in type 2 diabetes in adolescents. Prior to the mid-1990s, seeing type 2 diabetes in anyone younger than 18 was virtually unheard of. But with obesity levels rising, so is the rise of T2 diabetes, first in adults and now in kids. But it's not the same in both age brackets.
If you're reading this and you have type 2 diabetes, you'll want to pay special attention. More than 80% of the children in the study had at least one family member with type 2 diabetes. Yes, T2 is highly genetic and those who are predisposed are more likely to see this surfacing at a younger age.
The TODAY Study - Why and How
The TODAY study set out to compare treatment options for newly diagnosed youths aged 10 to 17 in twelve clinics around the country. When the study kicked off in 2004, there were only two drugs available to treat type 2 diabetes in the 18-and-under crowd: metformin and insulin. Turns out, the study shows neither of them are really that great.
"You need to realize that children are not small adults," Dr. Kenneth Copeland, an investigator from Oklahoma University, explained in an interview at the ADA's Scientific Sessions in Philly. "They actually have different physiological responses to drugs."
There are actually two problems going on in teens with type 2 diabetes, Copeland explained. First, puberty brings on a whole host of hormones and metabolic changes, causes all teens — even the so-called "normal" non-diabetic ones — to have insulin resistance. These hormones slow down once we reach adulthood, so in very real terms, the body of a teen and the body of an adult are not the same and won't react the same way to the same drugs.
The effect of growth hormones can be seen clearly in teens with type 1 who have persistent spikes in fasting blood sugar readings. All adolescents have this problem, but the pancreases of non-diabetics compensate for insulin resistance by pumping out more insulin.
The second problem is that a severely overweight or obese teenager whose body cannot compensate for insulin resistance often has family genetics and lifestyle contributing to good old fashioned type 2 diabetes. So some teenagers are essentially dealt a double-whammy: type 2 diabetes and puberty at the same time. Not only do teens have to work against the fast food and video game industry, but they also have their own bodies fighting against them (all those diagnosed with type 1 when young are likely nodding in empathy).
In the TODAY study, investigators looked at 699 adolescents in three randomly divided groups, given:
- Metformin only
- Metformin + Avandia (more on that in a sec...)
- Metformin + Lifestyle intervention
The most success came was observed in the Metformin + Avandia group, with only 38% of the group failing the treatment. What does failure mean? In the context of this study, failure meant the teen had to go on insulin to manage their blood sugars because their A1c remained too elevated.
Right now many of you are probably thinking: isn't Avandia banned? Well, it isn't banned in the U.S., despite controversy over possible heart health risks. And those warnings hadn't even surfaced yet when the study began in 2004. But Avandia is so heavily restricted now that there's almost no point in even mentioning it as a treatment possibility — especially for youths.
While Metformin is usually the number one go-to drug for adults with type 2 diabetes, the drug actually failed in half the teens in that sub-section within a year. It wasn't much better for Metformin + intensive lifestyle change, which had a 46% failure rate.
There are no clear reasons why Metformin failed so severely in teens with diabetes. Adherance (read: "noncompliance") wasn't a factor, Copeland clarified. "In terms of pill taking, we followed that closely and the pill taking was really quite good. All three groups took more than 80% of their pills, which is as good as we would expect in clinical practice."
A look into genetics is also needed to understand why Metformin failed, Copeland said. "There were biological difference because of the racial analysis. The African-Americans in the Metformin only groups, not only did they fail, but they failed dramatically more than Hispanics or whites, and they failed earlier. There are genetic reasons that we don't understand just yet."
We've known for a while that racial differences play a role in who gets type 2 diabetes, but now it appears that those differences also play a role in which medications work best.
Even though Metformin failed in half of teens, it remains the first recommendation for treating type 2 diabetes in adolescents.
(So, half are put on a path to failure, with docs knowing it probably won't work? Now that's sad.)
"What We Learned"
"What we learned was that Metformin alone is associated with a fairly rapid and frequent failure of control with in the first year," Copeland said. "It necessitated another agent. What other agent is open for discussion. The FDA and Pharma desperately need to test new oral drugs in children." Copeland also suggests that this means teens with type 2 need the "aggressive" treatment of insulin injections, rather than remaining on just Metformin.
Researchers believe that if teens can manage their type 2 diabetes successfully while getting over the "hump" of puberty's insulin resistance, many of them will be able to come off drugs entirely once they are in their early twenties. Of course, some of them remain type 2, but others are able to "reverse" their diabetes. In the TODAY trial, some participants who have been in the trial for all six years now have a normal, non-diabetic A1c and fasting blood glucose.
"Does that mean they're cured?" I asked Dr. Copeland.
He explained that it depends on how you define "cured." A similar debate rages on for people with type 2 diabetes who go off pills by managing with diet and exercise. Copeland suggests the way to think about it is that they are "in remission," and if they gain the weight back, they are almost guaranteed to have type 2 diabetes again. Although they might not have the pubescent insulin resistance, they still have the markers for type 2 diabetes.
Social Circumstances, Yo!
It wasn't just T2 and obesity that these kids had in common. The vast majority were from low-income families and a minority, with 41% Hispanic and 32% African-American. The teen participants frequently dealt with family dysfunction, often in contact with authorities or child services, often missed school, had poor communication and relationships with their parents, and less than 50% were living with both biological parents. So their socioeconomic and family circumstances undoubtedly played a role in their health status. But at least it was a pretty level playing field here, since almost every participant had some "outside struggles" to deal with alongside their diabetes.
With this research having been freshly completed, and even more analysis of the data currently underway, researchers are discovering even more questions to ask. The main question that remains: if teens are taking their type 2 medications the way they are supposed to, why aren't they working and what can we do about it?
The TODAY study set out to shed some light on what has been mostly a guessing game to date: what meds work best for treating T2 in kids? What it seems to have uncovered so far is more evidence that meds alone are not the answer, and that even "lifestyle interventions" only work if they are tailored to patient's individual struggles... But you probably knew that.