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HbA1c Variability a Predictor for Macrovascular Complications in Type 2’s

HbA1c variability may not impact CVD…. 

The extent and duration of hyperglycemia, is a major risk factor for both micro and macrovascular complications of diabetes. HbA1c variability relates to changes in glycemia over longer periods of time, which can result in change in HbA1c from one visit to the next. Robust evidence links HbA1c variability to the risk of microvascular complications in both type 1 and type 2 diabetes. However, association of HbA1c variability with CVD is less clear. In this study, researchers assessed the independent association of HbA1c variability with CVD, either total or by vascular bed.

The authors used the data collected at the baseline visit for the RIACE Italian Multicenter Study an observational, prospective cohort study on the impact of estimated glomerular filtration rate (eGFR) on morbidity and mortality from CVD in type 2 diabetes. A total of 15,773 Caucasian patients with type 2 diabetes were analyzed. The patients had a median (IQR) age and duration of diabetes at enrolment of 68 (61–74) and 14 (7–23) years, respectively, and a male/female ratio of 57/43. Multiple HbA1c values (3 to 5) serially measured at intervals of 6–12 months during the 2-year period preceding the enrolment were available from 9 centers for a total 8,290 patients (52.6% of the entire cohort). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. CVD risk factors and complications were determined as part of the baseline assessment using standardized protocols across study centers.

This cross-sectional analysis did not show a significant association of CVD with HbA1c variability, whereas events were independently associated with average HbA1c. HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications.

Based on the results of this article, the authors conclude that HbA1c variability does not have a great impact on macrovascular complications in patients with type 2 diabetes.

Practice Pearls:
  • Robust evidence links HbA1c variability to the risk of microvascular complications in both type 1 and type 2 diabetes.
  • The association of HbA1c variability with CVD is unclear.
  • Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD.

Cardiovascular Diabetology, July 2013