OBJECTIVE: The purpose of this study was to determine the prevalence of and risk factors for diabetic neuropathy in a Canadian First Nation population. RESEARCH DESIGN AND METHODS: This was a community-based screening study of 483 adults. Measures included glucose, A1C, cholesterol, triglycerides, homocysteine, hypertension, waist circumference, height, weight, and foot examinations. Neuropathy was defined as loss of protective sensation determined through application of a 10-g monofilament. RESULTS: Twenty-two percent of participants had a previous diagnosis of diabetes, and 14% had new diabetes or impaired fasting glucose (IFG). The prevalence of neuropathy increased by glucose level: 5% among those with normal glucose levels, 8% among those with new IFG and diabetes, and 15% among those with established diabetes (P < 0.01). Those with neuropathy were more likely to have foot deformities (P < 0.01) and callus (P < 0.001) than those without neuropathy. Among those with dysglycemia (>or=6.1 mmol/l), the mean number of foot problems for those with insensate feet was 3 compared with 0.3 among those with sensation (P < 0.001). In multivariate logistic regression female sex, low education, A1C, smoking, and homocysteine were independently associated with neuropathy, after controls for age. CONCLUSIONS: Neuropathy prevalence is high, given the young age of our participants (mean 40 years) and was present among those with undiagnosed diabetes. The high number and type of foot problems places this population at increased risk for ulceration; the low level of foot care in the community increases the risk. Homocysteine is a risk factor that may be related to lifestyle and requires further investigation.