The Diabetes Control and Complications Trial Research Group Long-term effect of diabetes and its treatment on cognitive function

New England Journal of Medicine (Impact Factor: 55.87). 05/2007; 356(18):1842-52. DOI: 10.1056/NEJMoa066397
Source: PubMed


Long-standing concern about the effects of type 1 diabetes on cognitive ability has increased with the use of therapies designed to bring glucose levels close to the nondiabetic range and the attendant increased risk of severe hypoglycemia.
A total of 1144 patients with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study were examined on entry to the DCCT (at mean age 27 years) and a mean of 18 years later with the same comprehensive battery of cognitive tests. Glycated hemoglobin levels were measured and the frequency of severe hypoglycemic events leading to coma or seizures was recorded during the follow-up period. We assessed the effects of original DCCT treatment-group assignment, mean glycated hemoglobin values, and frequency of hypoglycemic events on measures of cognitive ability, with adjustment for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss due to peripheral neuropathy, and (to control for the effects of practice) the number of cognitive tests taken in the interval since the start of the DCCT.
Forty percent of the cohort reported having had at least one hypoglycemic coma or seizure. Neither frequency of severe hypoglycemia nor previous treatment-group assignment was associated with decline in any cognitive domain. Higher glycated hemoglobin values were associated with moderate declines in motor speed (P=0.001) and psychomotor efficiency (P<0.001), but no other cognitive domain was affected.
No evidence of substantial long-term declines in cognitive function was found in a large group of patients with type 1 diabetes who were carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia. ( number, NCT00360893.)

Download full-text


Available from: Gail Musen, Oct 09, 2014
  • Source
    • "Furthermore, mild to moderate speed-related cognitive decrements are consistently found (Brands et al., 2005; Jacobson et al., 2007; Wessels et al., 2008). Cumulative hyperglycaemia is hypothesised to be related to T1DM-related cerebral compromise (Jacobson et al., 2007; Wessels et al., 2008). As the retina shares NeuroImage: Clinical 5 (2014) 69–76 ⁎ Corresponding author at: VU University Medical Centre, Diabetes Centre/Department of Internal Medicine, Department of Medical Psychology, De Boelelaan 1117 — Room MF- D342, 1081 HV Amsterdam, The Netherlands. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Integrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network.
    Clinical neuroimaging 06/2014; 5. DOI:10.1016/j.nicl.2014.06.001 · 2.53 Impact Factor
  • Source
    • "In patients with DM, the effect of tighter glycemic control on cognitive function is inconsistent. Some studies have reported a benefit of improved control on cognitive decline [42, 43] while others have shown no difference [44]. In the ADDITION study, cognitive decline in patients with screening-detected type 2 DM did not differ between intensive multifactorial treatment and routine care after 6 years [45]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus (DM) is associated with an increased risk of mild cognitive impairment, dementia and stroke. The association between DM and dementia appears to be stronger for vascular cognitive impairment than for Alzheimer's disease, suggesting cerebrovascular disease may be an important factor in cognitive impairment in DM. Although the exact mechanisms by which DM affects the brain remain unclear, changes to brain vasculature, disturbances of cerebral insulin signaling, insulin resistance, glucose toxicity, oxidative stress, accumulation of advanced glycation end products, hypoglycemic episodes, and alterations in amyloid metabolism may all be involved. Cognitive impairment and dementia associated with DM may also be mediated via vascular risk factors, in particular brain ischemia, the occurrence of which can have an additive or synergistic effect with concomitant neurodegenerative processes. To date, no drug has been approved for the treatment of vascular dementia and there are no specific pharmacological treatments for preventing or reducing cognitive decline in patients with DM. Most focus has been on tighter management of vascular risk factors, although evidence of reduced cognitive decline through reducing blood pressure, lipid-lowering or tighter glycemic control is inconclusive. Tailored, multimodal therapies may be required to reduce the risk of cognitive dysfunction and decline in patients with DM. The use of pleiotropic drugs with multimodal mechanisms of action (e.g., cerebrolysin, Actovegin) may have a role in the treatment of cognitive dysfunction and their use may warrant further investigation in diabetic populations.
    Neurological Sciences 04/2014; 35(7). DOI:10.1007/s10072-014-1797-2 · 1.45 Impact Factor
  • Source
    • "During hypoglycemia, lack of glucose supply to neurons can lead to confusion, brain damage (12), seizures (13,14), and even death. Indeed, 6–10% of deaths in young people with type 1 diabetes are directly attributable to hypoglycemia (15–17). It has been hypothesized that abrupt cardiac arrhythmias contribute to severe hypoglycemia–induced sudden death. "
    [Show abstract] [Hide abstract]
    ABSTRACT: For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10-15mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia-induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia-induced arrhythmias and overall mortality. α-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response.
    Diabetes 07/2013; 62(10). DOI:10.2337/db13-0216 · 8.10 Impact Factor
Show more