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OBJECTIVE -The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation.RESEARCH DESIGN AND METHODS -CBF was examined in 26 diabetic (aged 61.6 Ϯ 6.6 years) and 25 control (aged 60.4 Ϯ 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO 2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla.RESULTS -The diabetic group had smaller global white (P ϭ 0.006) and gray (P ϭ 0.001) matter and larger CSF (36.3%, P Ͻ 0.0001) volumes than the control group. Regional differences were observed for white matter (Ϫ13.1%, P ϭ 0.0008) and CSF (36.3%, P Ͻ 0.0001) in the frontal region, for CSF (20.9%, P ϭ 0.0002) in the temporal region, and for gray matter (Ϫ3.0%, P ϭ 0.04) and CSF (17.6%, P ϭ 0.01) in the parieto-occipital region. Baseline regional CBF (P ϭ 0.006) and CO 2 reactivity (P ϭ 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P Ͻ 0.0001). Higher A1C was associated with lower CBF (P Ͻ 0.0001) and greater CSF (P ϭ 0.002) within the temporal region.CONCLUSIONS -Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes. Diabetes Care 30:1193-1199, 2007D iabetes is a prevalent condition associated with substantial morbidity attributed to vascular complications (1). Diabetes alters endothelial function (2) and permeability of the bloodbrain barrier, thus affecting microcirculation and regional metabolism (3).Studies in type 1 diabetes have shown that the fronto-temporal cortex and periventricular white matter (3) are more affected by diabetic metabolic disturbance. Single proton emission computed tomography (SPECT) studies suggest that chronic hyperglycemia alters cerebral blood flow (CBF) in the frontal, temporal, parietal, occipital, and cerebellar regions of interest (ROIs) (4,5). Vasoreactivity to acetazolamide is not homogeneous, with a majority of hypoperfused and some hyperperfused ROIs (6). White matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI) (7) have been associated with arteriolosclerosis, arising as consequences of aging, diabetes, and other cardiovascular risk factors (8,9). Vascular and neurodegenerative changes in these structures have consequences for regional perfusion, cognitive impairment, and balance in elderly people with type 2 diabetes (10,...

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OBJECTIVETo assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors.RESEARCH DESIGN AND METHODSCross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup.RESULTSA high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter.CONCLUSIONSThe Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.

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