Prevalence of Structural Central Nervous System Abnormalities in Early-Onset Type 1 Diabetes Mellitus

Ho, Margaret S.; Weller, Narelle J.; Ives, F. Jay; Carne, Christine L.; Murray, Katherine; vanden Driesen, Rohan I.; Nguyen, Thai P.; Robins, Peter D.; Bulsara, Max; Davis, Elizabeth A.; Jones, Timothy W.

doi:10.1016/j.jpeds.2008.03.005

« Previous Next »The Journal of Pediatrics
Volume 153, Issue 3 , Pages 385-390, September 2008

Prevalence of Structural Central Nervous System Abnormalities in Early-Onset Type 1 Diabetes Mellitus

Margaret S. Ho, BA (Hons)
- Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
Narelle J. Weller, BappSc
- Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
F. Jay Ives, MBChB, FRANZCR
- SKG Radiology, Perth, Australia
Christine L. Carne, BSc, PGDip (Paediatrics), GradCert (Diab Educ)
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
Katherine Murray, BSc, PGDip HSc, GradDip (Diet)
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
Rohan I. vanden Driesen, FRANZCR
- Department of Radiology, Sir Charles Gairdner Hospital, Perth, Australia
Thai P. Nguyen, MBBS, FRANZCR
- Department of Diagnostic Imaging, Princess Margaret Hospital, Perth, Australia
Peter D. Robins, MBBS
- SKG Radiology, Perth, Australia
- St John of God HealthCare Subiaco, Perth, Australia
Max Bulsara, MSc
- Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
- School of Population Health, University of Western Australia, Perth, Australia
Elizabeth A. Davis, FRACP
- Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
Timothy W. Jones, MD, FRACP
- Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
- Endocrinology and Diabetes Services, Princess Margaret Hospital, Perth, Australia
- Reprint requests: Timothy W. Jones, MD, Endocrinology and Diabetes Services, Department of Diabetes and Endocrinology, Princess Margaret Hospital, GPO Box D184, Perth, WA 6840, Australia

Received 16 November 2007; received in revised form 29 January 2008; accepted 7 March 2008. published online 28 April 2008.

Objective

To characterize the effects of severe hypoglycemia on the developing brain in children with early-onset type 1 diabetes mellitus (T1DM).

Study design

Children diagnosed with T1DM before age 6 years were studied. Those with prospectively monitored severe hypoglycemia (coma/seizure; n = 32) were compared with age-matched peers (n = 30) with no history of such events using magnetic resonance imaging. Glycemic control (evaluated based on glycated hemoglobin [HbA_lc] level), episodes of diabetic ketoacidosis (DKA), and clinical variables were monitored continuously since diagnosis in all subjects.

Results

Mean HbA_lc from diagnosis and the duration of T1DM were similar in those with and without a history of severe hypoglycemia (9.0% ± 0.9% vs 8.8% ± 0.9%; 7.2 ± 2.7 years vs 6.7 ± 2.3 years). A high prevalence of central nervous system (CNS) structural abnormalities was detected (29%), and mesial temporal sclerosis (MTS) was detected in 16% of the total sample (n = 62). The presence of MTS was not associated with a history of severe hypoglycemia or DKA. Analysis of brain matter volumes suggested relatively less gray matter density in those subjects with a history of severe hypoglycemia.

Conclusions

Early age of onset of T1DM per se is associated with a high incidence of CNS abnormalities, particularly MTS, suggesting hippocampal damage. Early-onset severe hypoglycemia may have an effect on gray matter volume.

Abbreviations: CNS, Central nervous system, DKA, Diabetic ketoacidosis, ES, Effect size, HbA_lc, Glycated hemoglobin, MRI, Magnetic resonance imaging, MTS, Mesial temporal sclerosis, T1DM, Type 1 diabetes mellitus, VBM, Voxel-based morphometry