Neurophysiological Evidence for Altered Higher Brain Functions in NIDDM

Abstract

OBJECTIVE To investigate neurophysiological alterations of higher brain function in patients with NIDDM. RESEARCH DESIGN AND METHODS Auditory P300 event-related potentials were recorded in 60 NIDDM patients who had no evidence of stroke, dementia, or any other neurological illnesses. The P300 wave latencies in diabetic patients were compared with those in neurologically healthy control subjects, with consideration of clinical parameters and diabetic complications. RESULTS Diabetic patients had significantly longer P300 latencies than control subjects. Seven diabetic patients had pathologically prolonged P300 values. There was a trend toward longer P300 latencies in diabetic patients with retinopathy and in those with HbA1 of ≥10%; the differences between these diabetic subgroups and control subjects were both statistically significant. However, three of seven diabetic patients with abnormal P300 latencies had no retinal lesions, and no significant correlation was observed among diabetic patients between P300 latencies and HbA1 levels. Peripheral neuropathy, nephropathy, blood glucose levels, and disease duration appeared not to correlate with P300 alterations. CONCLUSIONS These findings suggest the presence of central nervous pathological processes in NIDDM that affect higher brain functions, as assessed by P300 latencies. Our findings also suggest that microangiopathy and metabolic derangement during the preceding 4- to 8-week period may contribute in small part to the pathophysiology of this central nervous involvement.

Circumscribed cognitive dysfunction in middle-aged adults with type 2 diabetes.

“…Consistent with that prediction are reports indicating that young or middleaged adults with a history of poor metabolic control or diabetes-associated biomedical complications are more likely to show longer brainstem auditory-evoked potential or P300 latencies (17,48) as well as white matter abnormalities on magnetic resonance imaging (49)(50)(51)(52). Children with type 1 diabetes duration of at least 2 years also show longer brainstem auditoryevoked potential latencies, which are correlated with disease duration, long-term HbA 1 , and hypoglycemic events (53).…”

“…Data on the relationship between type 2 diabetes and cognitive function in middle-aged adults are far more controversial. Neurophysiological measures of brain activity during the performance of cognitive tasks have demonstrated consistently that middle-aged adults with type 2 diabetes have longer P300 latencies, which are indicative of abnormal brain function (17,18). On the other hand, the relatively few studies of cognitive function in adults Ͻ65 years of age have, with few exceptions (4,18), failed to find evidence of diabetes-associated cognitive dysfunction (19)(20)(21).…”

Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications

“…We found that the incidence of complications-particularly retinopathy, predicted poorer performance on measures of psychomotor efficiency that are known to be adversely affected by cerebral white matter diseases like multiple sclerosis, Binswanger's disease, and alcoholism [58]. Although we did not use either neurophysiological or neuroimaging techniques to assess CNS integrity, others have reported relationships between diabetes-related biomedical complications and both slower BAEP conduction velocities [59,60] and increased incidence of white matter hyperintensities on MRI [39]. A more definitive test of the white matter hypothesis will require the pairing of traditional neuropsychological and electrophysiological measures of CNS function with newer imaging modalities, like diffusion tensor imaging [61], to map the integrity of white matter tracts in diabetic adults.…”

Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy

“…Reduced cognitive function, particularly with respect to memory and attention, has been identified in patients with poorly controlled diabetes [1][2][3], and epidemiological studies demonstrate a link between dementia and a diagnosis of diabetes [4,5]. Investigators have identified specific abnormalities in central nerve conduction that are more common in diabetes [6][7][8], but it is unclear if these abnormalities are linked to metabolic changes that occur as a result of chronic hyperglycemia or are caused by the vascular disease so common in patients with diabetes.…”