Key:
NZ    Nahida Zaman
JY    Dr Jack Yanovski

NZ    Good morning and welcome to Diabetes Radio.  I am your host Nahida Zaman.  I have with me on the line Dr Jack Yanovski.  Dr Yanovski, hello and a warm welcome to Diabetes Radio.

JY    Thank you.

NZ    Doctor, you are the Chief of the Section on Growth and Obesity at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.  Can you please give our listeners some information about your clinical background and research focus?

JY    I am a Paediatric Endocrinologist here at the NIH and I have been working on obesity related issues for a little over 20 years trying to understand the causes and consequences of paediatric obesity and also what we can do to treat that.

NZ    Doctor, your recent research culminated in the publication of an original paper in the ADA journal Diabetes Care.  The article was published in the November 2011 issue of Diabetes Care and was titled Longitudinal Study of Depressive Symptoms and Progression of Insulin Resistance in Youth at Risk for Adult Obesity.  Doctor, why did your group decide to conduct a study of depressive symptoms and progression of insulin resistance?

JY    The development of insulin resistance, as I am sure all of your listeners know, is a major precursor for the appearance of type II diabetes which has been an increasing problem even in adolescence so we were trying to understand some of the factors that might predispose to the development of that disorder.  Of course obesity is a major one but in addition to that the adult literature suggested that certain psychological factors such as depressive symptoms were important predictor factors for who went on to develop type II diabetes and in fact when depression was treated for improvement in the degree of insulin resistance in people independent of their body composition, that is how much fat and lean they had so we wondered if the same was true in paediatric populations, in particular in the adolescent group which is a time of particular insulin resistance due to puberty so we wanted to know if, having had depressive symptoms early on in childhood would predict the worsening of insulin resistance in adolescence.

NZ    What was your original hypothesis?

JY    Original hypotheses were that children who expressed particular depressive symptoms in childhood at ages of 6 to 12 would be showing greater degree of insulin resistance in adolescence about five years later.

NZ    And what were the objectives of your study?

JY    Our objectives were primarily to understand factors involved in the development of insulin resistance in adolescence and we thought that many factors might be important in the development of insulin resistance including body composition but also psychological factors like insulin resistance.

NZ    Doctor, how was your study designed?

JY    Our study was designed as a prospective longitudinal evaluation.  We studied almost 200 children at baseline between the ages of 6 and 12 intensively so they were brought in for fasting blood work and evaluations and then followed longitudinally for this study an average of about six years.  The intention was to re-draw blood samples five years after the visit but there is always a little bit of play between the visits and using the baseline characteristics which included psychological evaluations of depressive symptoms, we were able to examine the predictive power of depressive symptoms independent of their degree of adiposity of baseline.

NZ    And what were the results?

JY    We found that, looking at the child depression inventory scores at baseline predicted who was going to have worse insulin resistance over five years later.  In fact at baseline the group that increased depressive symptoms had elevated insulin resistance so they had a degree of insulin resistance that was higher on average and also if we defined it categorically in terms of what would be called elevated resistance measured by the Homer Index then about twice as many of the kids with high depressive symptoms had elevated Homer indices at baseline and then when examined almost six years later, if we compared the group with lower and elevated depressive symptoms, again the Homer Index was considerably elevated in those who had higher baseline depressive symptoms, even accounting for important variables including the sex and race of the child, family history of type II diabetes, baseline age, baseline BMI, change in BMI over time and the amount of years’ follow-up so on average the group with elevated baseline depressive symptoms had a markedly abnormal Homer insulin resistance index over four whereas the others with lower depressive symptoms had essentially a normal, on average anyway, a normal Homer insulin resistance index five years later adjusted for those other characteristics.  The insulin resistance was greater in those with baseline elevated depressive symptoms because of increases in both the glucose and the insulin levels in the group with elevated depressive symptoms.  The insulin levels were about 30% increased over those who had lower depressive symptoms at baseline but the glucose was also increased so that the average glucose in those with elevated depressive symptoms in adolescence was over 90 mg/dL versus a normal value of about 85 in the group with lower depressive baseline symptoms and that really lets us know that the group with elevated depressive symptoms was really moving in the direction of developing type II diabetes since we know that as glucose increases pretty much lineally the risk of diabetes increases later one.

NZ    Dr Yanovski, what conclusions can be drawn from these results?

JY    I think the conclusion that can be drawn is that adolescence is a particularly important period for the development of insulin resistance and depressive symptoms so this is a uniquely important time for understanding the role that these factors may have in ultimately causing type II diabetes but in addition these data suggest that there may be ways that we might help prevent type II diabetes by working not only on factors like body weight but also on psychological symptoms and signs so that it may well be that those who have elevated depressive symptoms, if they are appropriately treated, might suffer less risk of developing type II diabetes in the future and that has actually led us to begin a clinical trial here at the NIH examining this hypothesis, recruiting children with some degree of depression at baseline and also a family history of diabetes so that they are at increased risk for developing the disorder and observing what happens when we give them a programme intended to reduce those depressive symptoms and that study has just begun and we hope to have some results in a couple of years.

NZ    Doctor, your study results reveal that depressive symptomatology predicts the progression of insulin resistance during child and adolescent development.  Independent of changes in BMI, were you surprised by these results?

JY    We were a little bit surprised because we did not realise how powerful the role of these depressive symptoms would be dependent of body mass index.  We knew that other studies had suggested that depressive symptoms lead folks to gain more weight over time, including children so we thought that most of the effective depressive symptoms would be moderated, would be mediated really through the changes in body mass so it was a little bit of a surprise how strong the effect was.  Of course these were all predictors and they could just be not really causative but related so it is very important to test the opposite hypothesis that in fact the depressive symptoms are merely following along with the insulin resistance and not really causative of the changes and that is why treatment studies changing depressive symptoms and seeing what happens to insulin resistance are so important to understand this.

NZ    Doctor, how do you potentially see your results helping to shape routine clinical practice?

JY    Right now it is still in the experimental phase but if it does turn out in our clinical trial that improving depressive symptoms actually helps reduce insulin resistance then hopefully then could help prevent the onset of type II diabetes, that could be a very important clinical improvement for the lives of children at risk for this disorder.

NZ    Doctor, did your research help shed light into whether early intervention to decrease elevated depressive symptoms ameliorates later development of insulin resistance and lessens the risk of type II diabetes?

JY    I think our research highlights the importance of understanding the relationship between depressive symptoms and insulin resistance.  We have shown that they are associated or related but we still have to show whether decrease in depressive symptoms will improve insulin resistance later on.

NZ    Dr Jack Yanovski, thank you so much for taking the time to speak with us today.