OBJECTIVE: Chronic hyperglycemia relates to the occurrence of diabetic polyneuropathy (DPN), but has not yet been shown to relate to its overall severity In addition, the degree and duration of hyperglycemia, which measure of chronic hyperglycemia is most predictive of defined levels of severity of DPN, and which other putative risk factors are involved remain unknown. RESEARCH DESIGN AND METHODS: In a longitudinal study of 264 diabetic individuals in Rochester, MN, risk factors and other diabetic complications assessed at regular intervals during an average of approximately 7 years were tested for their association with a composite score of severity of DPN at the last examination. RESULTS: In multivariate analysis, diabetic retinopathy severity level (at last examination), mean ln(24-h proteinuria x duration of diabetes), and mean GHb were the main covariates for severity of DPN (R2 = 0.33). Excluding markers of microvessel and macrovessel disease, the independent risk factors were mean In(GHb x duration of diabetes), GHb, and type of diabetes (R2 = 0.23). CONCLUSIONS: We found that diabetic microvessel disease, chronic hyperglycemia exposure, and type of diabetes are associated with severity of DPN, and we believe these factors are implicated in its cause. Each of the five markers of microvessel disease was a strong covariate for severity of DPN. Mean GHb predicts severity of DPN better than duration of diabetes, and the latter predicts severity of DPN better than mean fasting plasma glucose. Knowing the severity of microvessel disease, the degree of chronic hyperglycemia exposure, and the type of diabetes provides useful information to evaluate whether a coexisting polyneuropathy and its severity is probably due to diabetes.

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