DESCRIPTION (provided by applicant): This epidemiologic study of patients with diabetes mellitus (DM), impaired HbA1c and without DM (non-DM) aims at studying the frequency and heterogeneity of diabetic neuropathies by variety, characteristic features, course and emphasizing morbidity, disability, and adverse outcomes and their risk factors in population-based cohorts of different ethnicity, i.e., Caucasian (RDNS), Mdewakanton Dakota Sioux (MDS), Hispanic American (HA), and Somalian American (SA) cohorts. Additionally, we will study the clinical and neuropathological features of intercurrent and problematic neuropathies referred to Mayo Clinic Rochester (MCR) to improve classification, understanding of mechanisms, and treatment. We hypothesize and have new information indicating: 1) diabetic neuropathy is heterogeneous, implying different underlying mechanisms; 2) there is no safe level of impaired glycemic exposure; and 3) some varieties have an immune basis and treatment for these may become available. Our specific aims are: 1) to estimate the frequencies of varieties of neuropathy (and of other diabetic complications), emphasizing staged severities, adverse outcomes, morbidity and disability, and difference among the four ethnic cohorts; 2) to assess risk factors for types and severities of neuropathy (and other diabetic complications) and adverse outcomes (e.g., sudden cardiac death, neuropathic pain, plantar ulcers, Charcot joints, and other); 3) to model the influence of glycemic exposure testing the hypothesis (and some early evidence) that even impaired HbAlc values equivalent to FPG levels of 110 to 126 mg/dl (impaired fasting glucose [IFG]) over long times is associated with diabetic complications; 4) to ascertain using matched cohort studies whether intercurrent neuropathies such as the severe debilitating radiculoplexus neuropathies (and the intercurrent immune multifocal neuropathies) occur more frequently in patients with DM than in background populations; and 5) to study the heterogeneity of underlying pathologic alterations and mechanisms of intercurrent and multifocal diabetic neuropathies with severe morbidity in a bank of nerve tissue from problematic cases referred to us at MCR.
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