HbA(1c) Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

OBJECTIVE: To examine the association of hemoglobin (Hb) A(1c) variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS: Serial (3–5) HbA(1c) values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA(1c) variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS: Median and interquartile range of average HbA(1c) (HbA(1c)-MEAN) and HbA(1c)-SD were 7.57% (6.86–8.38) and 0.46% (0.29–0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA(1c) parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA(1c)-SD adds to HbA(1c)-MEAN as an independent correlate of microalbuminuria and stages 1–2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3–5 albuminuric CKD, whereas HbA(1c)-MEAN is not. The opposite was found for DR, whereas neither HbA(1c)-MEAN nor HbA(1c)-SD affected nonalbuminuric CKD. CONCLUSIONS: In patients with type 2 diabetes, HbA(1c) variability affects (albuminuric) CKD more than average HbA(1c), whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications.