Hyperglycemia and Hypoglycemia in Young Children with Type 1 Diabetes: Does it matter?
As all families with young children with type 1 diabetes know, it is a balancing act to try to keep blood glucose levels within a defined range. Our Diabetes team at Children's National Medical Center recommends different ranges based on the age of the child. Generally, for children up to age 5 years, the suggested goal range is between 100-200 mg/dl. For children from ages 5 until about 12 the suggested goal range is 70-180 mg/dl; And for adolescents and young adults the range is 70-150 mg/dl (or lower upper range based on preference). We have previously discussed that there are subtle changes in short term memory and cognitive skills in the presence of hyperglycemia and hypoglycemia and that it was (and is) important to try to avoid major fluctuations in blood sugar for additional reasons other than euglycemia and a good hb A1c. This is very tough for caregivers of young children.
Toddlers and young children are notorious for erratic eating patterns and thus it is very difficult to accurately determine the amount of insulin to inject prior to eating. We often recommend that in young children it might be wiser to give rapid acting insulin after eating to better determine the number of carbohydrates that were actually ingested and avoid low blood sugars! This method, however, contributes to a greater amount of blood glucose fluctuations, which is not ideal. As young children grow, there is a tremendous amount of remodeling in the brain where there are multiple changes in synaptic connections and new pathways are thus continually developed. The brain also physically grows during these phases of development.
In a very timely paper published in Diabetes Care, Volume 34, July 2011, pages 1458-1462, (The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children) my colleagues Darrell Wilson and Bruce Buckingham (et.al.) from Stanford University attempted to determine if frequent episodes of both hyperglycemia and hypoglycemia lead to neurocognitive deficits and structural (or functional) changes in the anatomy of the brain. The authors performed a feasibility and cross-sectional study in which children aged 3 to 10 years of age with type 1 diabetes for at least 6 months were evaluated. Much to my satisfaction (especially after my recent blog on research and informed consent) children older than 7 years of age were asked to sign informed consents as well. Information in regard to blood glucose control (downloaded meters, pumps, etc.) was obtained as well as hb A1c values. In regards to hypoglycemia, parents were queried about the occurrence and frequency of seizures secondary to severe neuroglycopenia (low blood sugars leading to unconsciousness or seizures). Significant hyperglycemic events were determined by admission and treatment for DKA. Age matched controls were compared to these participants. 28 children with type 1 diabetes and 17 matched children without diabetes were enrolled in the study
A. Neuropsychologic testing was performed by using:
1. Wechsler Preschool and Primary Scale of Intelligence (WPPSI, 3rd edition) to evaluate general intellectual functioning in children 3-5 years old
2. Wechsler Intelligence Scale for children (WISC, 4th edition) for children 5-10 years old
3. NEPSY: (Developmental NEuroloPSYcological Assessment) to evaluate "executive function, memory/attention, motor and visual-spatial domains"
4. Blood sugars were measured before testing to make certain that all levels were between 80-250 mg/dl prior to neuropsychological testing
5. Testing was stopped if the children developed symptoms and signs of low blood sugars
1. Children were given materials to teach them what to expect during the MRI scanning procedure
2. Blood sugars were in the range of 100-250 mg/dl prior to the MRI
3. Parents and technicians observed for symptoms and signs of hypoglycemia
What were the results and conclusions of this small study? (40/45 children completed all neuropsychologic testing and MRI scanning.)
1. There were no statistically significant differences were noted in general intellect, executive function, memory/attention, motor and visual spatial domains between those with type 1 diabetes and matched controls
2. The verbal comprehension score was lower in type 1 diabetes children with higher hb A1c values
3. Children with type 1 diabetes and history of seizures related to hypoglycemia had lower WISC processing speed, full-scale IQ score, working memory, and perceptual reasoning
4. MRI findings:
a. Similar brain volumes between the type 1 diabetes and control group
b. Children with type 1 diabetes showed a significantly altered pattern of white matter development related to control subjects as well as reduction in gray matter and white matter in those that experienced seizures
c. No differences of hippocampus (structure of brain involving memory) volume between those children with type 1 diabetes with history of seizures and control children
TAKE HOME MESSAGES
1. This is a small feasibility study and there were insufficient numbers of subjects to make broad generalizations. Further research with an increased number of participants will be necessary to make evidence-based and statistical conclusions.
2. There is accumulating evidence to indicate that significant hyperglycemic and hypoglycemic patterns do affect both brain structure and function and attention needs to be directed to avoiding both extremes.
3. Vigilance in monitoring blood sugars remains appropriate; thus increasing the need for increased testing of blood sugars and consideration of continuous glucose monitoring systems as well.
4. Redirection of efforts to approve the artificial pancreas ASAP to assist in keeping blood sugars in appropriate range, minimizing fluctuations.
5. Understanding why diabetes teams are anxious in regard to both extremes of hypoglycemia and hyperglycemia.