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Hyperglycemia associated with slowed brain matter growth in young children with type 1 diabetes
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Continued exposure to hyperglycemia could be detrimental to brain development in young children with type 1 diabetes, with slower brain matter growth over time compared with children without the condition, according to research published in Diabetes.
Nelly Mauras, MD, of Nemours Children’s Clinic, Jacksonville, Florida, and colleagues from the multicenter Diabetes Research in Children Network (DirecNet), detected differences in total and regional growth in brain areas involved in complex sensorimotor processing and cognition.
Nelly Mauras
“We have been keenly interested in the role of abnormal glucose levels on diabetes complications; the younger the children are when they get diabetes, the more we worry about their complications,” Mauras told Endocrine Today. “Hyperglycemia is potentially damaging to the developing brain.”
Changes in matter, not cognition
The researchers longitudinally assessed gray and white matter volume in children aged 4 to 9 years with type 1 diabetes (n=144; average duration, 2.5 years) and without (n=72); one-fourth of the control group were siblings of the patient group.
All children underwent unsedated high-resolution structural brain MRIs at baseline and 18 months, Mauras said. “Using state-of-the-art software, the imaging coordinating center at Stanford was able to compartmentalize the brain images into different gray and white matter regions..”
Comprehensive age-specific neurocognitive testing was done at the same time points, Mauras explained. “We performed tests on their IQ, memory, cognition and mental processing skill — basically their ability to reason.”
For patients with type 1 diabetes, continuous glucose monitoring (6 days, adding up to 1,440 blood glucose readings per patient per day) and HbA1C measurements were performed every 3 months over the course of the study, she said.
“We found the rate of brain growth, both for gray and white matter, was slower in children with diabetes than that of healthy age-matched controls,” Mauras said.
Gray matter areas, including left precuneus, right temporal, frontal and parietal lobes, and right medial-frontal cortex, showed less growth in patients with diabetes. White matter areas, including splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps and inferior-frontal fasciculus, also showed slower growth in children with diabetes.
No between-group differences were observed in cognitive and executive functions scores at 18 months.
“These differences in the brain that affect a multiplicity of processing functions were not accompanied by changes in cognition, which is good news,” Mauras said. “But the fact that marked differences were seen gives us some concern.”
Unanticipated findings
The observed changes in brain matter were associated with higher cumulative hyperglycemia and glucose variability; they were not linked with hypoglycemia, which Mauras said could be due to the paucity of hypoglycemic events during the study.
Based on previous knowledge that brain development problems are more likely when children are diagnosed at younger ages and exposed to more hypoglycemia, a main concern until now has been avoiding low blood glucose.
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“We often let the blood sugars run on the high end by decreasing the amount of insulin we give these youngsters or feeding them more, so we avoid hypoglycemia altogether,” Mauras said.
“We anticipated the greatest association was going to be with hypoglycemia incidence, but we found it was actually hyperglycemia that showed the greatest association with these brain findings.”
The DirecNet investigators called the findings “remarkable” because the patient age group was so young and the period with diabetes so short; Mauras said providers have generally believed, and told parents, it takes at least 10 years to develop diabetes complications.
“The study participants were just diagnosed within a 3-year timeframe, which is a relatively short duration for the disease to show structural brain changes,” Karen Winer, MD, of the National Institute of Child Health and Human Development (NICHD), an investigator on the study, told Endocrine Today.
Karen Winer
With four papers published earlier in 2014 demonstrating detailed differences in brain structure between the cohorts with diabetes and controls, the DirecNet investigators have received an NIH grant, through NICHD, to continue following the children longitudinally over the next 5 years.
“Is the brain ‘plastic?’ Does it recover? Does it get worse?” Mauras asked. “How do these cognitive tests change over time, now that these kids are getting older and progressing through puberty?” — by Allegra Tiver
For more information:
Nelly Mauras, MD, can be reached at Nemours Children’s Clinic, 807 Children’s Way, Jacksonville, FL 32207; email: nmauras@nemours.org.
Karen Winer, MD, can be reached at 6100 Executive Blvd, Room 4B11, MSC 7510, Bethesda, MD, 20892-7510; email: winerk@mail.nih.gov.
DirecNet includes investigators at Nemours Children’s Clinic (Jacksonville, Florida), Stanford University (Stanford, California), Washington University (St. Louis, Missouri), University of Iowa (Iowa City, Iowa), Yale University (New Haven, Connecticut) and the Jaeb Center for Health Research (Tampa, Florida).
Disclosure: Please see study for full list of disclosures.
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