A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes

Johan Wadén, Carol Forsblom, Lena M Thorn, Daniel Gordin, Markku Saraheimo, Per-Henrik Groop, Finnish Diabetic Nephropathy Study Group, Johan Wadén, Carol Forsblom, Lena M Thorn, Daniel Gordin, Markku Saraheimo, Per-Henrik Groop, Finnish Diabetic Nephropathy Study Group

Abstract

Objective: Recent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetes microvascular complications. However, these results might have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetes complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study.

Research design and methods: A total of 2,107 patients in the FinnDiane Study had complete data on renal status and serial measurements of A1C from baseline to follow-up (median 5.7 years), and 1,845 patients had similar data on cardiovascular disease (CVD) events. Intrapersonal SD of serially measured A1C was considered a measure of variability.

Results: During follow-up, 10.2% progressed to a higher albuminuria level or to end-stage renal disease, whereas 8.6% had a CVD event. The SD of serial A1C was 1.01 versus 0.75 (P < 0.001) for renal status and 0.87 versus 0.79 (P = 0.023) for CVD in progressors versus nonprogressors, respectively. In a Cox regression model, SD of serial A1C was independently associated with progression of renal disease (hazard ratio 1.92 [95% CI 1.49-2.47]) and of a CVD event (1.98 [1.39-2.82]) even when adjusting for mean A1C and traditional risk factors. Interestingly for CVD, mean serial A1C itself was not predictive even though SD of A1C was.

Conclusions: In patients with type 1 diabetes, A1C variability was not only predictive of incident microalbuminuria and progression of renal disease but also of incident CVD events.

Figures

FIG. 1.
FIG. 1.
A: Kaplan-Meier survival curves for any progression in renal status (defined as any increase in albuminuria level or progression to ESRD) by quartiles of SD of serially measured A1C values. B: Kaplan-Meier survival curves for a CVD event (coronary event, stroke, peripheral vascular event) by quartiles of SD of serially measured A1C values.
FIG. 2.
FIG. 2.
A: Kaplan-Meier survival curves for any progression in renal status (defined as any increase in albuminuria level or progression to ESRD) according to mean and SD of serial A1C above and below the population median. B: Kaplan-Meier survival curves for a CVD event (coronary event, stroke, peripheral vascular event) according to mean and SD of serial A1C above and below the population median.

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