Visual Abstract

C-peptide levels and visit to visit glucose variability (GV) are associated with cardiovascular disease (CVD) in both type 1 and type 2 diabetes (T2D). Although low C-peptide levels, reflecting beta cell failure, are associated with greater GV, the relationship between these two risk factors and CVD is unknown. We tested whether excess GV represents a link between low C-peptide levels and CVD in advanced T2D. Fasting C-peptide levels at baseline, GV (between visit coefficient of variation of fasting glucose levels) and composite CVD events were determined in 1,558 participants of the Veterans Affairs Diabetes Trial. Those in the lowest quartile of C-peptide levels had highest GV which persisted after adjustment for study arm (intensive vs. standard glycemic control), and clinical and demographic CVD risk factors (Figure). Higher CVD risk was associated with low baseline C-peptide levels and higher GV (Figure). In a combined multivariate model, low-C-peptide levels and increased GV both remained significant predictors of CVD risk (Figure). The present data indicate that beta-cell dysfunction in advanced T2D is associated with greater GV and increased CVD risk. Increased GV however does not appear to explain the association between beta cell dysfunction and higher CVD risk. Low C-peptide levels may be used as biomarker of both increased CVD risk and GV in individuals with advanced T2D.


J. Koska: None. D. S. Nuyujukian: None. G. D. Bahn: None. J. Zhou: None. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc.


U.S. Department of Veterans Affairs (CSP465); National Institutes of Health (R01067690, 5R01094775)

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