Risk Factors for Decline in IQ in Youth With Type 1 Diabetes Over the 12 Years From Diagnosis/Illness Onset

Ashleigh Lin; Elisabeth A. Northam; George A. Werther; and Fergus J. Cameron

Disclosures

Diabetes Care. 2015;38(2):236-242. 

In This Article

Abstract and Introduction

Abstract

Objective This study examined illness-related change in intelligence quotient (IQ) in a cohort of youth with type 1 diabetes studied prospectively from disease onset in childhood to follow-up 12 years later in late adolescence/early adulthood.

Research Design and Methods Participants included type 1 diabetes patients (n = 95; mean age at follow-up 21.3 years) and healthy control participants (HCs; n = 67; mean age at follow-up 21.0 years) from a cohort followed prospectively. Measures included Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children-Revised, and Wechsler Abbreviated Scale of Intelligence and prospective collection of data on metabolic control history.

Results Young people with type 1 diabetes showed greater decline in verbal IQ (VIQ) and full-scale IQ (FSIQ), but not performance IQ (PIQ), than HCs. Within the diabetes group, a younger age at diabetes onset was associated with a decline in PIQ and FSIQ (P ≤ 0.001). A history of hypoglycemic seizures was associated with a decline in VIQ (P = 0.002). Long-term metabolic control was not associated with changes in IQ. Interaction terms were not significant, suggesting no moderating effect of one diabetes-related variable over another.

Conclusions The presence of diabetes may negatively influence some aspects of IQ over time. Specific illness risk factors, such as an earlier age of disease onset and a history of hypoglycemic seizures, appear to put the young person at greater risk. Academic progress of children identified as at risk should be monitored and educational supports provided if necessary.

Introduction

A constant supply of glucose is critical for normal cerebral metabolism.[1,2] Thus the brain is one of the major organ systems affected in type 1 diabetes, as glucose homeostasis is frequently disrupted, even in well-controlled diabetes.[3] Developing brains have high cerebral energy needs associated with brain growth and neural pruning and may be more sensitive than adults to glucose fluctuations.[3] It is important to document specific illness-related risk factors for brain changes in young people with type 1 diabetes. Better understanding of the impact of childhood-onset disease on the central nervous system (CNS) will facilitate evidence-based pediatric management regimens and proactive interventions to minimize academic underachievement and functional impairment.

There is a growing literature documenting pathophysiological CNS changes[4–13] and neurocognitive deficits[14–23] in youth with type 1 diabetes. However, attempts to identify specific diabetes-related risk factors for CNS compromise have produced inconclusive findings. An association between cognitive deficits and an early age of disease onset is a robust finding,[14] but associations between glycemic perturbations and CNS effects are less consistent. Given the alteration in conscious state that accompanies severe episodes, the focus traditionally has been on hypoglycemia as the explanation for cognitive deficits in children with type 1 diabetes. However, neuroimaging findings are inconsistent, with some studies finding no association between hypoglycemia history and structural brain changes[4,12] while others report positive correlations, but with little consistency between the brain regions affected.[5,7,9–11] Meta-analytic cognitive studies also provide contrasting findings, with one reporting positive association between hypoglycemia history and cognitive deficit[23] and another finding no association.[14]

There is now increasing concern that chronic exposure to hyperglycemia may impact on the developing brain, although research findings to date are inconsistent and probably reflect, in part, difficulty in obtaining accurate reports of lifetime metabolic control, particularly when measured retrospectively. Volumetric reductions in both gray and white matter and altered diffusion tensor imaging (DTI) parameters have been associated with greater exposure to hyperglycemia in several studies,[4,6,10–13] but not in others.[5,7–9] Similarly, an association between long-term poor metabolic control and cognitive deficits was found in some[5,16–18,20,22] but not other[9,14] studies. There is now compelling evidence that type 1 diabetes impacts upon the developing brain, but our understanding of the causal mechanisms that underlie CNS changes is limited. This makes it difficult to weigh the relative neurotoxicity of glycemic extremes and to tailor management regimens accordingly.

Controlled, longitudinal studies are particularly informative in documenting illness-related changes in cognitive function. The only study to date that has examined within-subject change in intelligence quotient (IQ) from childhood to follow-up in early adulthood[24] is limited by the fact that initial assessment of IQ occurred years after diabetes onset. Thus participants had already been exposed to a period of glycemic dysregulation before baseline assessment. Our group has previously reported that youth with type 1 diabetes had lower full-scale IQ (FSIQ) and verbal IQ (VIQ) scores than healthy community control participants (HCs) when assessed cross-sectionally 12 years after disease onset.[9] In the current study, we used data from diabetes onset and from follow-up 12 years later to examine change in IQ scores in youth with type 1 diabetes and HCs. Within the diabetes group, we examined associations between changes in IQ and age of diabetes onset, history of serious hypoglycemia, and longer-term metabolic control.

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