A NUANCED PICTURE
Exposing the Underlying Mechanisms of Type 2 Diabetes
Don ’ t eat for a while and your blood sugar level goes down . Eat a candy bar and it ticks up . That ’ s the basic principle of testing insulin and glucose physiology : either measure fasting blood glucose levels or administer glucose to see how the body reacts .
“ But if I drink a glucose solution , my blood sugar might go to 95 , while in prediabetic kids it might go to 145 ,” says Kristen Nadeau , MD , MS , Director of Research for Pediatric Endocrinology at Children ’ s Hospital Colorado . “ There are limitations to oral testing .”
Those limits make it difficult for diabetes researchers to get an accurate read on insulin secretion in response to a stimulus , due to the many variables at play . Working with Phil Zeitler , MD , PhD , Chief of Pediatric Endocrinology and Medical Director of the Children ’ s Colorado Clinical and Translational Research Center , Dr . Nadeau has developed a way to leapfrog those variables .
Infusing children intravenously , sometimes overnight , Dr . Nadeau uses established “ clamp ” techniques to set a glucose or insulin level and maintain it at a constant over time . This method creates a highly accurate , individualized overview of insulin secretion and response – and one
Dr . Nadeau can also measure against oral tests to examine the variables themselves .
“ When you drink a glucose solution , part of what happens is dependent on secretion of gut hormones ,” says Dr . Nadeau . “ By combining oral studies with IV studies , we can also see what the gut hormones are doing .”
The action of gut hormones is one of many mechanisms of the disease Dr . Nadeau and her team are studying . Other study targets include insulin resistance in type 1 diabetes and the potentially preventative effect of early , aggressive treatment of prediabetes , among several others .
“ It ’ s not that the clamp technique is new ,” says Dr . Nadeau . “ The novelty is adapting it to studying kids with abnormal blood sugar . That ’ s quite unique .”
It won ’ t be for long . Dr . Nadeau is training researchers from pediatric centers around the country to use this approach . Beyond her own endeavors , these methods will help pediatric researchers develop a more nuanced picture than ever before of the underlying mechanisms of type 2 diabetes , how the disease develops in kids , and how it might be treated in the future .
Restoring Insulin Secretion study
Dr . Nadeau serves as national principal investigator of the Restoring Insulin Secretion ( RISE ) study , which has employed intravenous clamping methods to explore the effect of treating kids with prediabetes and abnormal blood glucose levels with diabetes drugs early on .
“ It ’ s one of the most intensive studies of its kind that ’ s ever been done in youth ,” says Dr . Nadeau .
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DIABETES & ENDOCRINOLOGY
Now in its fifth year , the study hypothesizes that early , aggressive treatment may help return some durable function to overtaxed pancreatic beta cells , potentially allowing kids to undergo a period of intensive treatment and then discontinue medication – perhaps permanently . RISE concluded at the end of 2016 , and Dr . Nadeau expects to publish preliminary data soon .