Modeling Chronic Glycemic Exposure Variables as Correlates and Predictors of Microvascular Complications of Diabetes

Abstract

OBJECTIVE -The degree to which chronic glycemic exposure (CGE) (fasting plasma glucose [FPG], HbA 1c [A1C], duration of diabetes, age at onset of diabetes, or combinations of these) is associated with or predicts the severity of microvessel complications is unsettled. Specifically, we test whether combinations of components correlate and predict complications better than individual components.RESEARCH DESIGN AND METHODS -Correlations and predictions of CGE and complications were assessed in the Rochester Diabetic Neuropathy Study, a population-based, cross-sectional, and longitudinal epidemiologic survey of 504 patients with diabetes followed for up to 20 years.RESULTS -In multivariate analysis, A1C and duration of diabetes (and to a lesser degree age at onset of diabetes but not FPG) were the main significant CGE risk covariates for complications. A derived glycemic exposure index (GE i ) correlated with and predicted complications better than did individual components. Composite or staged measures of polyneuropathy provided higher correlations and better predictions than did dichotomous measures of whether polyneuropathy was present or not. Generally, the mean GE i was significantly higher with increasing stages of severity of complications.CONCLUSIONS -A combination of A1C, duration of diabetes, and age at onset of diabetes (a mathematical index, GE i ) correlates significantly with complications and predicts later complications better than single components of CGE. Serial measures of A1C improved the correlations and predictions. For polyneuropathy, continuous or staged measurements performed better than dichotomous judgments. Even with intensive assessment of CGE and complications over long times, only about one-third of the variability of the severity of complications is explained, emphasizing the role of other putative risk covariates. Diabetes Care 29:2282-2288, 2006C hronic glycemic exposure (CGE) (the degree and duration of plasma hyperglycemia) is thought to be the important modifiable risk covariate for the complications of diabetes (1-3). This view comes from cohort studies (4 -8) and from trials with clamping hyperglycemia at two levels of glycemic control (9 -12). Although it has been debated whether a CGE threshold exists (13,14), such a threshold is assumed in estimating the lowest level of CGE that induces complications. This level of CGE may then be used to set minimal criteria for the diagnosis of diabetes itself (1,2,13). At issue, however, is how CGE should be estimated. Orchard et al. (13,15) evaluated the severity and duration of hyperglycemia and complications in young people with type 1 diabetes, but the CGE variable that was preset (the percentage of HbA 1c [A1C] was more than or equal to the minimal criteria for diabetes times duration of diabetes in months) did not predict complications any better than its components.Here, we study CGE and complications evaluated intensively and comprehensively in the Rochester Diabetic Neuropathy Study (RDNS). The following are specific questions ad...

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