Long-term effect of diabetes and its treatment on cognitive function

New England Journal of Medicine (Impact Factor: 54.42). 05/2007; 356(18):1842-52. DOI: 10.1056/NEJMoa066397
Source: PubMed

ABSTRACT 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.)

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Available from: Gail Musen, Oct 09, 2014
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    • "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. "
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    • "Perhaps most importantly in the present context, the peripheral lack of insulin seen in T1DM may not be reflected in lowered brain insulin ((Stranahan, Arumugam et al. 2008); as might be expected if the brain is a source of insulin not reliant on pancreatic synthesis) and experimental induction of T1DM does not produce cognitive effects until several months after peripheral insulin production is impaired (Biessels, Kamal et al. 1996; Kamal, Biessels et al. 2000), suggesting that other factors (such as vascular effects, reduced brain glucose supply, altered glucocorticoid levels or many other possible effector mechanisms) may underlie cognitive changes in T1DM while brain insulin signalling may be at least relatively spared. Finally, the impact of T1DM on cognitive function in humans, as opposed to animal models, is small or absent in several studies (Group 1991; Group 1993; Jacobson, Musen et al. 2007; Kodl and Seaquist 2008; Wrighten, Piroli et al. 2009); even where present, the decline seen in T1DM is much slower than the effects of T2DM (Brands, Biessels et al. 2007), and may be due to nonspecific vascular and/or neurodegenerative effects, further arguing for separate evaluation of the two disease states. Hence, we shall focus here on brain insulin signaling and on T2DM, with the aim of determining whether alterations in brain insulin signaling may provide an explanation for the cognitive and neural effects of the disease. "
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    • "However, while the T1DM patients exhibited cognitive decline over the course of the 12 year study, the authors also noted that cognitive performance of their patient population was within the normal range, an observation consistent with reports from other investigators (Brands et al., 2006). Indeed, a recent report from the Diabetes Control and Complications Trial (DCCT) that provided an 18 year evaluation of T1DM patients failed to identify significant cognitive impairments in this patient population, even when taking into account such factors as the degree of glycemic control and severity of hypoglycemia episodes (Jacobson et al., 2007). Unlike the studies in T1DM patients, most studies suggest that T2DM patients experience cognitive decline [For reviews, see (Strachan et al., 1997; Starr and Convit, 2007; Reijmer et al., 2010; Wrighten et al., 2008)]. "
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