A1C Variability Linked to Diabetes Complications

Variability in glycosylated hemoglobin (A1C) predicts the development of complications in patients with type 1 diabetes, say researchers from Finland in the November Diabetes.

"Consider not only the level of A1C, but also the A1C variability profile of a patient as a risk indicator of diabetic complications," Dr. Johan Waden from Helsinki University Central Hospital, told Reuters Health. "In our study, cardiovascular events were related to A1C variability but not to the actual A1C level."

Dr. Waden and colleagues used data from the observational, longitudinal Finnish Diabetic Nephropathy (FinnDiane) Study to analyze the effect of both the mean A1C and the variability of A1C on the prediction of type 1 diabetes complications.

Complete data on renal status and serial measurements were available for 2107 patients, and data on cardiovascular disease events were available for 1845 patients.

The intrapersonal mean of serially measured A1C was 8.5% with a variability (standard deviation) of 0.78, the authors report.

The variability in A1C increased according to baseline renal status, from 0.75 in patients with normoalbuminuria to 0.82 with microalbuminuria, 0.89 with macroalbuminuria, and 0.79 with end-stage renal disease.

A1C variability was significantly higher in patients who progressed to cardiovascular disease events (0.87) than in those who did not (0.79), the researchers note.

A1C variability was greater in all subgroups of patients who worsened in renal status, the investigators say, and the results were similar when coefficient of variation was used as the measure of A1C variability.

Higher A1C variability was associated with younger age, lower age at onset of diabetes, shorter duration of diabetes, lower insulin sensitivity, dyslipidemia, higher baseline A1C, both current and ever smoking, lower socioeconomic class, and lower leisure-time physical activity.

In multivariate models, the standard deviation of serial A1C measurements predicted progression in renal status and cardiovascular disease events independently of mean serial A1C.

"Our data include only patients with type 1 diabetes, and our findings are not necessarily applicable to type 2 diabetes," Dr. Waden cautioned. "Our data are purely observational, and the causal relationships have to be further studied."

"If A1C variability plays a role in the development of diabetic nephropathy, we would expect an association also with other microvascular diabetic complications (retinopathy and neuropathy) since the risk factor profile, especially the glycemic control, is to a large extent similar to that of nephropathy," Dr. Waden said.

"We showed that patients with signs of a disadvantageous lifestyle (low socioeconomic status, smoking, and low physical activity) had higher A1C variability," Dr. Waden added. "Other additional factors such as diet and psychosocial aspects would also be interesting to study. Infections may be implicated and this could also be further studied."

Diabetes. 2009;58:2649-2655.