Study: Children with Type 2 Diabetes Benefitting from Bariatric Surgery

Study: Children with Type 2 Diabetes Benefitting from Bariatric Surgery


– Hi, I’m Dr. Thomas Inge,
Chief of Pediatric Surgery and Surgical Director
of the Bariatric Center here at Children’s Colorado. We’re here today to talk about a study that was recently completed, that examined diabetic
kidney disease outcomes in teenagers with Type 2 diabetes, that were treated either
surgically or medically. I’m here today with Petter Bjornstad, one of our endocrinologists, to tell us more about the study. – Thanks Tom, I really
appreciate the opportunity to discuss our research
here with you today. First, I wanted to just give
a little bit of background about the study and why it’s
important, if that’s okay? – [Dr. Inge] Sure. – Type 2 diabetes in youth, as you know, is rapidly increasing in parallel
with the obesity epidemic. And youth with diabetes have earlier onset of complications, including diabetic kidney disease, but also higher rates of complications than adult-onset Type 2 diabetes and also their peers with Type 1 diabetes. And also I think it’s
important that we remember that diabetic kidney disease, remains the leading cause
of end-stage kidney disease and dialysis in the U.S. – Sure, so certainly something that we would like to reverse– – [Petter] Right. – Or to provide an
excellent treatment for. – Right, and that’s exactly the problem ’cause the medical options to treat or impede the development
of diabetic kidney disease in youth-onset Type 2 are so limited. And that’s why I think the
data we will discuss here today are so exciting, because we are looking at a different type of therapy, bariatric surgery, and how that affects diabetic kidney disease. – Sure, maybe it would
be good for the listeners to kind of walk us through what happens with traditional best medical therapy for diabetes and then the renal
complications of it as well. – Right, so in youth-onset Type 2, the only real FDA approved
medications are insulin, metformin and more recently
a GLP-1 receptor agonist which was approved in June of this year. The more novel therapies
like SGLT2 inhibitor are not yet approved for
the pediatric age group. And really the only
medications we can consider to impede the development
of diabetic kidney disease would be an ACE inhibitor. So, it’s quite limited. – And so these drugs that are for diabetes are typically very good I understand that, at managing
either the insulin resistance or a hyperglycemia. – [Petter] Right. – But then there is this other issue of all the comorbidities
that go along with diabetes. How do they respond usually to therapy? – So the SGLT2 inhibitor that I mentioned, has shown in large
cardiovascular outcome trials to actually impede the development of diabetic kidney
disease and heart outcomes like, for instance, the CREDENCE Trial. But again, as I mentioned
these are unfortunately not approved for use in pediatrics. So we also don’t know whether the findings that we are seeing in
adult trials will translate to the pediatric population. – Sure, and as a surgeon, I have certainly been impressed
with some of the research work that has gone on
looking at the effects of surgery for adult Type 2 diabetes. – [Patter] Right. – And I think that for this age group, we are really sort of in
the dark historically on, are the results of surgery
for Type 2 diabetes similar or different than what
can be expected in adults? What’s irrelevant to that
issue and how surgery appears to affect Type 2
diabetes in adolescents, what were your interesting
observations in this study? – Right, first, I just wanna
give a little background of the study design.
– [Dr. Inge] Sure. – So people understand how we did this. So this was a secondary analysis as you know, or a post hoc
analysis where we looked at the rates of diabetic kidney disease over five years in two groups. So one group of adolescents
with Type 2 diabetes underwent bariatric surgery, and then
one group of adolescents with Type 2 that received
standard medical therapy. And we drew these participants
from two large cohorts. One of them being Teen-LABS,
obviously you know that one well being the PI of Teen-LABS, which is a group of severely obese youth both with or without Type 2 diabetes who all underwent bariatric surgery. – Either gastric bypass or
sleeve gastrectomy, correct. – Right, and then the
other group, we drew from was the TODAY study, which included only
adolescents with Type 2 that were randomly assigned
to metformin therapy alone or rosiglitazone in
combination with metformin, or in combination with
lifestyle interventions and then insulin added on as
indicated for glycemic failure. And then we obviously
needed to make sure that these two groups were fairly similar, so we used frequency matching and what we did was
identified 30 participants in Teen-LABS that had Type 2 diabetes, and then we used frequency matching to create a similar
cohort in the TODAY study. And we used age between 13 to 18, BMI equal to or greater than 35, in addition to sex and ethnicity. And our frequency matching
yielded 63 participants in TODAY, in addition to the 30 in Teen-LABS. – Sure, so let’s get right into it then. What do you think were the
most highlighted findings or what do you think the
most important findings were? – The most important findings
is in terms of the diabetic kidney disease outcomes, and what we saw over five
years is in Teen-LABS, which are the adolescents that
underwent bariatric surgery, for instance with elevated
albumin excretion, which is previously known
as microalbuminuria, one of the more traditional markers of early diabetic kidney disease, the prevalence in Teen-LABS
went from a baseline of 27% to 5% at five-year follow-ups. That’s a drop of 22%. In contrast, in TODAY, which are the group receiving standard medical
therapy, it went from 21% at baseline to 43% at
five-year follow-ups. So, it actually increased
by the same amount as the decrease was in
Teen-LABS was at 22%. And we saw exactly the same trajectories also with another marker of
early diabetic kidney disease called hyperfiltration, which
is an abnormally elevated glomerular filtration rate or GFR. And what we saw is that
that significantly decreased over time in Teen-LABS and then it increased over time in TODAY. – Now this hyperfiltration, it’s sort of the kidney overworking–
[Petter] Right. – And I get that you’re
worried about that, but why? – It’s a great question. So it’s thought to be one
of the earliest phenotypes of diabetic kidney disease, and why it’s problematic,
the data behind that is really just from animal models and from mechanistic studies. But it seems like the
energy demand of the kidney to sustain such a high function at a super physiological rate, leads to an excessive oxygen consumption. And this excessive oxygen consumption, when you have diabetes
and you have an impaired ability to generate energy or ATP because of insulin resistance, mitochondrial dysfunction
leads to a metabolic imbalance between energy need and energy delivery. And this can lead to hypoxia and then loss of the
smallest functional units of the kidneys, called nephrons. And this can drive the progression of
diabetic kidney disease. – So that’s interesting. And now back to the first finding– – [Petter] Right. – Having to do with the
kidney, the proteinuria– – [Petter] Right.
– Why do we worry about that? – So again, that’s a really
important risk factor and marker of early diabetic kidney disease. But perhaps equally important is it’s a really strong risk factor for cardiovascular disease, and it has also been linked to mortality. – Got it. And now, what are the other findings that you may have been
surprised by in this study? – Right, so we also,
rather than just looking at the different trajectories and prevalence, we also wanted to look at what is the group difference between the Teen-LABS and TODAY? So we performed a multi-variable
logistic regression models and our results were really surprising. – Looking for predictors
of how these findings might have evolved? – Right, and also looking
at the difference. And what we found is that in a fully adjusted model, where we adjusted for baseline age, sex, BMI, A1C, insulin sensitivity, use of
anti-hypertensive medications – the odds of having
elevated albumin excretion at five-year follow-up,
in Teen-LAB participants, were 27-fold lower than the participants receiving standard medical therapy in TODAY. And we saw the same significant difference with hyperfiltration, where
the Teen-LAB participants had a 17-fold lower odds
of having hyperfiltration at five-year follow-ups, and that was definitely surprising. Although, we did expect bariatric surgery to have nephroprotective effects, we were surprised by the
magnitude of the effects. – Sure, I think you also
looked at some mediators– – [Petter] We did.
– The possible mediators of this effect on the kidneys. – We did. So we were curious to figure out why was bariatric surgery
associated with such huge kidney protection and what were
the median age behind this? And one of the things we looked
at was improvement in A1C. ‘Cause in Teen-LABS, we saw that A1C significantly
improved in this cohort. So it went from a baseline of 6.8%, so that’s preoperatively, to 5.2% one year post-op. And then it increased modestly to 5.9, but it did remain in
the non-diabetic range. – Sure, on average. – Right, in contrast, in TODAY it went from a baseline of 6.2 all the way to 8.8% at five-year. – And this is while escalating
medical therapy as well. – Exactly, so, we obviously were curious if improvement in A1C could
explain the group affect we saw with surgery versus medical therapy. And it was a strong mediator, but it didn’t account for everything. So we also looked at other
important risk factors like insulin sensitivity,
improvement in triglycerides, body mass index and to a lesser degree than glycemic control, they
were also important mediators, but even collectively none of them completely accounted for
the group effect we saw with bariatric surgery versus
standard medical therapy. – So do you think we
might be able to call this some special effective surgery or just something we didn’t
measure in the study perhaps? – So maybe something we
didn’t measure in the study. Obviously we don’t know
what we don’t know, obviously right?
– [Dr. Inge] Right. – But I do think there are
other important factors at play. – Physiologic changes
– [Petter] Exactly. – that happen with surgery, it’s not just a plumbing rearrangement. – Exactly, I think there are
important metabolic factors. – Sure, so what do you think the clinical implications then are? What should the person seeing
these patients with diabetes in adolescents take away from this? – Right, so I think the take-home message of this important study is that in severely obese youth
with Type 2 diabetes, bariatric surgery was associated with a several-fold lower odds
of diabetic kidney disease, which is a really important
complication of Type 2 diabetes compared to standard medical therapy. And I think those data
support an indication for bariatric surgery for severely obese youth
with Type 2 diabetes. And obviously, as you know
better than me, bariatric surgery incurs significant costs,
comorbidities and risk, but I do think in carefully
selected candidates that the benefits may outweigh the risk at specialized centers like
Children’s Hospital Colorado. But I also think we need to determine whether less invasive surgical methods like vertical sleeve
gastrectomy can provide the same kidney benefits as we saw with gastric bypass, since the majority of the participants in this study underwent gastric bypass. – Sure, that makes sense. We really did a secondary analysis– – [Petter] Right.
– In this study. It certainly does beg
for what is the next, the next approach here from a
research standpoint as well. – Right, and I do think
that since we discovered that the traditional risk factors didn’t completely account
for the group effect we saw with surgery versus
standard medical therapy. I think we have to look closer and we have to use more
sophisticated methods. – [Dr. Inge] True. – So one of the studies
we have going on locally, we are using state-of-the-art imaging, we are using clams, et cetera to get a better resolution
of what’s going on in terms of kidney metabolism, but also whole body metabolism. – So Petter, I really wanna
thank you for your time today, very interesting study. And for those of you who
might wanna learn more about what we’re doing here
at Children’s Colorado, please visit us on our website.

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