Impact of diabetes and its treatment on cognitive function among adolescents who participated in the Diabetes Control and Complications Trial

Gail Musen, Alan M Jacobson, Christopher M Ryan, Patricia A Cleary, Barbara H Waberski, Katie Weinger, William Dahms, Meg Bayless, Nancy Silvers, Judith Harth, Neil White, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, Gail Musen, Alan M Jacobson, Christopher M Ryan, Patricia A Cleary, Barbara H Waberski, Katie Weinger, William Dahms, Meg Bayless, Nancy Silvers, Judith Harth, Neil White, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group

Abstract

Objective: The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13-19 years at entry in the Diabetes Control and Complications Trial (DCCT).

Research design and methods: This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, approximately 18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition.

Results: There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis.

Conclusions: Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT00360893.

Figures

Figure 1
Figure 1
Changes in cognitive domains between DCCT baseline cognitive testing and follow-up testing (mean of 18 years after baseline) based on change in Z scores for intensive (□) vs. conventional (▪) treatment groups (A), frequency of severe hypoglycemia (coma or seizure) episodes (no episodes □, 1–5 espisodes ▒, or >5 episodes ▪) (B), and tertiles of mean A1C (

References

    1. DCCT Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986, 1993
    1. The Diabetes Control and Complications Trial Research Group: Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial. Ann Intern Med 124:379–388, 1996
    1. Austin EJ, Deary IJ: Effects of repeated hypoglycemia on cognitive function: a psychometrically validated reanalysis of the Diabetes Control and Complications Trial data. Diabetes Care 22:1273–1277, 1999
    1. Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, Burwood A, Weinger K, Bayless M, Dahms W, Harth J: Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356:1842–1852, 2007
    1. Huttenlocher PR, Dabholkar AS: Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 387:167–178, 1997
    1. Chugani HT: A critical period of brain development: studies of cerebral glucose utilization with PET. Prev Med 27:184–188, 1998
    1. Giorgio A, Watkins KE, Douaud G, James AC, James S, De Stefano N, Matthews PM, Smith SM, Johansen-Berg H: Changes in white matter microstructure during adolescence. Neuroimage 39:52–61, 2008
    1. Ferguson SC, Blane A, Wardlaw J, Frier BM, Perros P, McCrimmon RJ, Deary IJ: Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function. Diabetes Care 28:1431–1437, 2005
    1. Rovet JF, Ehrlich RM: The effect of hypoglycemic seizures on cognitive function in children with diabetes: a 7-year prospective study. J Pediatr 134:503–506, 1999
    1. Ryan C, Vega A, Drash A: Cognitive deficits in adolescents who developed diabetes early in life. Pediatrics 75:921–927, 1985
    1. Rovet J, Alvarez M: Attentional functioning in children and adolescents with IDDM. Diabetes Care 20:803–810, 1997
    1. Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA: Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset. Diabetes Care 24:1541–1546, 2001
    1. Gold AE, Deary IJ, Frier BM: Recurrent severe hypoglycaemia and cognitive function in type 1 diabetes. Diabet Med 10:503–508, 1993
    1. Malone JI, Hanna SK, Saporta S: Hyperglycemic brain injury in the rat. Brain Res 1076:9–15, 2006
    1. Diabetes Control and Complications Trial Research Group: Effects of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes: Diabetes Control and Complications Trial. J Pediatr 125:177–188, 1994
    1. White NH, Cleary PA, Dahms W, Goldstein D, Malone J, Tamborlane WV: Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). J Pediatr 139:804–812, 2001
    1. Steffes M, Cleary P, Goldstein D, Little R, Wiedmeyer HM, Rohlfing C, England J, Bucksa J, Nowicki M: Hemoglobin A1c measurements over nearly two decades: sustaining comparable values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications study. Clin Chem 51:753–758, 2005
    1. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group: Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 22:99–111, 1999
    1. DCCT Research Group, Jacobson A, Cleary P, Baker L: The influence of intensive treatment on quality of life outcomes in the Diabetes Control and Complications Trial. Diabetes Care 19:195–203, 1996
    1. Derogatis L: SCL-90 Administration, Scoring and Procedures Manual-I. Baltimore, John Hopkins Univ. Press, 1983
    1. Snedecor G, Cochran WG: Statistical Methods. 8th ed. Ames, Iowa State University Press, 1989
    1. Perantie DC, Wu J, Koller JM, Lim A, Warren SL, Black KJ, Sadler M, White NH, Hershey T: Regional brain volume differences associated with hyperglycemia and severe hypoglycemia in youth with type 1 diabetes. Diabetes Care 30:2331–2337, 2007
    1. Ryan CM, Becker DJ: Hypoglycemia in children with type 1 diabetes. Risk factors, cognitive function, and management. Endocrinol Metab Clin North Am 28:883–900, 1999
    1. Hyllienmark L, Maltez J, Dandenell A, Ludvigsson J, Brismar T: EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes. Diabetologia 48:412–419, 2005
    1. Musen G, Lyoo IK, Sparks CR, Weinger K, Hwang J, Ryan CM, Jimerson DC, Hennen J, Renshaw PF, Jacobson AM: Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry. Diabetes 55:326–333, 2006

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться