Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients.

Diabetes mellitus is associated with end-organ complications in the peripheral and central nervous system. It is unknown if these complications share a common aetiology, and if they co-occur in the same patient. The aim of the present study was to relate different measures of peripheral neuropathy in patients with type 2 diabetes mellitus (DM2) to cognition and brain MRI. A standardized neurological examination and questionnaire, neuropsychological examination and brain MRI were performed in 122 patients with DM2 and 56 matched controls. Measures of peripheral neuropathy were vibration threshold, a sensory examination sum score and the Toronto Clinical Neuropathy Scoring System. Neuropsychological test scores were expressed in standardized z-values across five predetermined cognitive domains. White matter lesions and cortical and subcortical atrophy were rated on MRI. Overall 38% of the patients with DM2 and 12% of the controls were classified as having any neuropathy (p<0.001). Patients with DM2 had a lower performance on the neuropsychological tests, more white matter lesions (p<0.01) and more atrophy (p<0.01) than controls. Within the DM2 group none of the measures of peripheral neuropathy was related to MRI abnormalities or cognitive dysfunction (linear regression analyses, adjusted for age, education, sex). We conclude that peripheral neuropathy in patients with DM2 is not related to cognitive dysfunction and brain abnormalities. This indicates that central and peripheral neurological complications of DM2 might have different etiologies.

Three families with polyneuropathy associated with monoclonal gammopathy.

OBJECTIVE: To report familial occurrence of polyneuropathy associated with monoclonal gammopathy. DESIGN: Case reports. PATIENTS: We describe 6 patients (3 pairs) with a polyneuropathy associated with IgM monoclonal gammopathy. Four of the 6 patients had a demyelinating polyneuropathy on neurophysiological examination. Three patients had elevated antibodies against myelin-associated glycoprotein. No duplication on chromosome 17 or a mutation on chromosome 1 was found in any family. CONCLUSION: Familial occurrence of polyneuropathy without the presence of hereditary motor and sensory neuropathy type I is a reason to search for the presence of monoclonal gammopathy.

Cerebral perfusion in relation to cognitive function and type 2 diabetes.

AIM/HYPOTHESIS: Underlying mechanisms for decreased cognitive functioning in patients with type 2 diabetes are unclear. In the general population, cerebral hypoperfusion is a risk factor for cognitive dysfunction and dementia. Reduced cerebral perfusion may account for cognitive impairments in diabetic patients relative to controls. METHODS: A total of 98 patients with type 2 diabetes and 47 control participants underwent neuropsychological evaluation. Total cerebral blood flow (CBF) was assessed non-invasively by measuring the volume flow in the internal carotid arteries and basilar artery with two-dimensional phase-contrast magnetic resonance angiography. Relative total CBF, a measure of mean total cerebral perfusion, was obtained by expressing total CBF per 100 ml brain parenchyma volume. RESULTS: Patients with type 2 diabetes performed worse on neuropsychological tests (p < 0.05). Total CBF per 100 ml brain parenchyma volume did not differ between participants with and without diabetes (difference -2.3 ml min(-1) 100 ml(-1); 95% CI -6.0, 1.3). In the entire group, total CBF per 100 ml brain parenchyma volume was positively associated with cognitive functioning (0.09 SD increase in composite z score per 10 ml min(-1) 100 ml(-1) increase in relative total CBF). This association was not affected by type 2 diabetes. CONCLUSIONS/INTERPRETATION: Although total CBF per 100 ml brain parenchyma volume was associated with cognitive functioning, it did not explain cognitive impairments in patients with type 2 diabetes relative to controls.

Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The determinants of cerebral complications of type 2 diabetes are unclear. The present study aimed to identify metabolic and vascular factors that are associated with impaired cognitive performance and abnormalities on brain MRI in patients with type 2 diabetes. METHODS: The study included 122 patients and 56 controls. Neuropsychological test scores were divided into five cognitive domains and expressed as standardised z values. Brain MRI scans were rated for white matter lesions (WML), cortical and subcortical atrophy, and infarcts. Data on glucose metabolism, vascular risk factors and micro- and macrovascular disease were collected. RESULTS: Patients with type 2 diabetes had more cortical (p < 0.001) and subcortical (p < 0.01) atrophy and deep WML (p = 0.02) than the control group and their cognitive performance was worse. In multivariate regression analyses within the type 2 diabetes group, hypertension (p < 0.05) and a history of vascular events (p < 0.01) were associated with worse cognitive performance, while statin use was associated (p < 0.05) with better performance. Retinopathy and brain infarcts on MRI were associated with more severe cortical atrophy (both p < 0.01) and statin use with less atrophy (p < 0.05). Insulin level and brain infarcts were associated with more severe WML and statin use with less severe WML (all p < 0.05). CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with modest impairments in cognition, as well as atrophy and vascular lesions on MRI. This 'diabetic encephalopathy' is a multifactorial condition, for which atherosclerotic (macroangiopathic) vascular disease is an important determinant. Chronic hyperglycaemia, hyperinsulinaemia and hypertension may play additional roles.

Cerebrovascular reserve capacity is preserved in a population-based sample of patients with type 2 diabetes mellitus.

BACKGROUND AND PURPOSE: Type 2 diabetes mellitus (DM2) is associated with an increased risk of stroke. DM2 is also associated with cognitive impairments. Vascular dysfunction, such as impaired cerebrovascular reserve capacity (CVR), may be a determinant of these changes, but previous studies on CVR in DM2 have provided variable results in selected populations of patients. We aimed to examine CVR in a population-based sample of DM2 patients. METHODS: The CO(2) reactivity of the middle cerebral artery was examined using transcranial Doppler ultrasonography in 81 DM2 patients and 38 controls. In DM2 patients CVR was correlated with diabetic parameters, vascular risk factors and cognitive functioning. RESULTS: CVR was similar in patients and controls (51 vs. 49%). Within the DM2 group, there was no statistically significant relationship between CVR and DM duration, HbA(1c), albuminuria, blood pressure, intima-media thickness and cognition. CVR tended to be lower in diabetic patients with retinopathy [46 vs. 55%, mean difference: -7.9 (confidence interval -18.0, 2.2)]. CONCLUSION: We conclude that CVR is not impaired in unselected patients with DM2 and probably does not, therefore, play a major role in the aetiology of cognitive impairment.