HbA1c Variability Linked to Nephropathy in Type 2 Diabetes

Fran Lowry

March 21, 2013

Fluctuations in glycated hemoglobin (HbA1c) are correlated with the development of nephropathy, but not retinopathy, in patients with type 2 diabetes, according to a new study published online March 14 in Diabetes Care.

Recent research has suggested that HbA1c variability is an independent risk factor for the development of diabetic retinopathy and nephropathy in people with type 1 diabetes, as well as microalbuminuria in patients with type 2 diabetes, write Giuseppe Penno, MD, from the University of Pisa, Italy, and colleagues. The aim of the current work was to examine these associations further in a large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian multicenter study.

This consisted of 15,933 white patients with type 2 diabetes. For this analysis, the researchers looked at 3 to 5 HbA1c values from 8260 patients (52.6% of the entire RIACE cohort) that were collected over a 2-year period before the participants entered the trial.

Patients' median age was 68 years, and the median duration of diabetes was 14 years (range, 7 to 23 years). Average HbA1c and HbA1c variability was calculated for each patient as the intraindividual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively.

Median and interquartile ranges of HbA1c-MEAN and HbA1c c-SD were 7.57% (range, 6.86% – 8.38%) and 0.46% (range, 0.29% – 0.74%), respectively.

HbA1c-SD added to HbA1c-MEAN was an independent correlate of microalbuminuria and stages 1 to 2 chronic kidney disease (CKD) and an independent predictor of macroalbuminuria, reduced estimated glomerular filtration rate (eGFR), and stages 3 to 5 albuminuric CKD, whereas HbA1c-MEAN was not correlated with these outcomes. The opposite was observed for diabetic retinopathy.

"This…analysis provides the first evidence of a wide spectrum of associations of average HbA1c and HbA1c variability with microvascular complications in subjects with type 2 diabetes, thus suggesting that different mechanisms might link glycemic control to microvascular abnormalities in these individuals," say Penno et al.

The fact that the patients had had diabetes for a long time and therefore likely had a worse cardiovascular-risk profile and a greater likelihood of having cardiovascular disease (CVD) is a limitation of the study, the authors point out. But they also note the strengths of their study, including the large cohort size, the contemporary data set, the completeness of the data, and the concurrent analysis of diabetic retinopathy and nephropathy.

"In patients with type 2 diabetes, HbA1c variability affects albuminuria and albuminuric CKD phenotypes independently of (or instead of) average HbA1c, even after adjustment for known risk factors for microvascular complications. On the contrary, HbA1c variability has no effects on diabetic retinopathy, which is mainly dependent on HbA1c," they conclude.

This study was supported by the Research Foundation of the Italian Society of Diabetology and the Diabetes, Endocrinology, and Metabolism Foundation, Eli Lilly, Takeda, Chiesi Farmaceutici, and Boehringer-Ingelheim.

Diabetes Care. Published March 14, 2013. Abstract

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