Objective: Our objective was to investigate whether type 2 diabetes mellitus (T2DM) influences neurodegeneration in a manner similar to Alzheimer disease (AD), by promoting brain β-amyloid (Aβ) or tau. Methods: We studied the cross-sectional associations of T2DM with cortical thickness, brain Aβ load, and CSF levels of Aβ and tau in a sample of people from the Alzheimer9s Disease Neuroimaging Initiative with diagnoses of AD dementia, mild cognitive impairment, and normal cognition. All (n = 816) received MRI, and a subsample underwent brain amyloid imaging (n = 102) and CSF Aβ and tau measurements (n = 415). Analyses were performed across and within cognitive diagnostic strata. Results: There were 124 people with T2DM (mean age 75.5 years) and 692 without T2DM (mean age 74.1 years). After adjusting for age, sex, total intracranial volume, APO ε4 status, and cognitive diagnosis, T2DM was associated with lower bilateral frontal and parietal cortical thickness (mL) (β = −0.03, p = 0.01). T2DM was not associated with ¹¹C Pittsburgh compound B standardized uptake value ratio (AU) in any brain region or with CSF Aβ₄₂ levels (pg/mL). T2DM was associated with greater CSF total tau (pg/mL) (β = 16.06, p = 0.04) and phosphorylated tau (β = 5.84, p = 0.02). The association between T2DM and cortical thickness was attenuated by 15% by the inclusion of phosphorylated tau. Conclusions: T2DM may promote neurodegeneration independent of AD dementia diagnosis, and its effect may be driven by tau phosphorylation. The mechanisms through which T2DM may promote tau phosphorylation deserve further study.

OBJECTIVE—The purpose of this study was to examine the natural history of peripheral arterial disease (PAD) complicating type 2 diabetes, in particular the influence of PAD on the risk of cardiac death and the adequacy of PAD risk factor management. RESEARCH DESIGN AND METHODS—The Fremantle Diabetes Study (FDS) was a prospective community-based observational study of diabetic patients recruited between 1993 and 1996. The present sample comprised the 1,294 FDS type 2 diabetic patients and a subgroup of 531 of these who had valid data at baseline and five or more subsequent consecutive annual reviews. Assessments consisted of a range of clinical and biochemical variables including the ankle/brachial index (ABI). PAD was defined as an ABI ≤0.90 at two consecutive reviews or any PAD-related lower-extremity amputation. RESULTS—The prevalence of PAD at study entry was 13.6% and the incidence of new PAD was 3.7 per 100 patient-years. Both prevalent and incident PAD was strongly and independently associated with increasing age, systolic blood pressure, total serum cholesterol, and especially smoking. Risk factor management improved but remained suboptimal during follow-up. An ABI of ≤0.90 was independently associated with an increased risk of cardiac death of 67%. CONCLUSIONS—Measurement of the ABI is a simple means of identifying PAD in diabetic patients. PAD is common in diabetic patients and predicts cardiac death. These data further support the role of regular screening for PAD in diabetes so that intensive management of vascular risk factors can be pursued.