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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, 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, 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.
Using a clamp to maintain and measure insulin levels
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."
Gut check: studying hormones, insulin resistance and early treatment
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 a range of 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.
Dr. Nadeau also leads the Restoring Insulin Secretion study
Dr. Nadeau serves as national pediatric 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.
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 pediatric enrollment concluded at the end of 2016, and Dr. Nadeau expects to publish preliminary data.