Predictive Ability of Visit-to-Visit Variability of HbA1c Measurements for the Development of Diabetic Kidney Disease: A Retrospective Longitudinal Observational Study

Abstract

Aims. This study is aimed at clarifying the relationship between visit-to-visit variability of glycated hemoglobin (HbA1c) and the risk of diabetic kidney disease (DKD) and to identifying the most useful index of visit-to-visit variability of HbA1c. Methods. This clinic-based retrospective longitudinal study included 699 Japanese type 2 diabetes mellitus patients. Visit-to-visit variability of HbA1c was calculated as the internal standard deviation of HbA1c (HbA1c-SD), the coefficient of variation of HbA1c (HbA1c-CV), the HbA1c change score (HbA1c-HVS), and the area under the HbA1c curve (HbA1c-AUC) with 3-year serial HbA1c measurement data, and the associations between these indices and the development/progression of DKD were examined. Results. Cox proportional hazards models showed that the HbA1c-SD and HbA1c-AUC were associated with the incidence of microalbuminuria, independently of the HbA1c level. These results were verified and replicated in propensity score (PS) matching and bootstrap analyses. Moreover, the HbA1c-SD and HbA1c-AUC were also associated with oxidized human serum albumin (HSA), an oxidative stress marker. Conclusions. Visit-to-visit variability of HbA1c was an independent risk factor of microalbuminuria in association with oxidative stress among type 2 diabetes mellitus patients. HbA1c-AUC, a novel index of HbA1c variability, may be a potent prognostic indicator in predicting the risk of microalbuminuria.

The Association Between Glycaemic Variability and Progression of Chronic Kidney Disease: a Systematic Review

“…Six studies reported duration of diabetes, with a mean duration of 9.80 years (SD ± 6.21) [21][22][23]. Six studies reported the median duration of diabetes, which ranged from 1 to 23 years [24][25][26][27][28][29].…”

“…The ethnic composition of the subjects was detailed in nine studies [21,22,[25][26][27][28][29][30][31]. The period of observation ranged from 0.5 to 10 years.…”

“…Glycaemic variability was assessed using HbA1c results in all the studies, although the definition of glycaemic variability varied between them. The majority of studies used the intrapersonal mean and standard deviation (SD) of HbA1c [19][20][21][22][23][24][25][26], two studies [27][28][29][30] used the coefficient of variation (CV) of HbA1c, and Yan et al [29] used glycaemic change score and area under the curve. Cumming et al [31] used three different metrics based on the area under the curve (AUC) for three different models related to a threshold value of an HbA1c of 7% (based on a minimum of 10 readings), as follows: (1) AUC of HbA1c values > 7%;…”

“…(2) AUC of HbA1c values above and below 7% combined; and (3) the difference in AUC of values > and < 7% (i.e., AUC for HbA1c > 7% minus the AUC for HbA1c < 7%). One study [29] also used clinically significant changes in HbA1c (> 0.5%, 5.5 mmol/ mol) to calculate a variability score, in addition to SD, AUC, and CV.…”

“…They found that patients who are in the highest HbA1c-CV group at baseline (3 years prior to assessment) had a greater risk of decline in kidney function (HR − 2.53, 95% CI − 3.28, − 1.78), compared to the second (HR − 1.73, 95% CI − 2.38, − 1.08) and third highest (HR − 0.99, 95% CI,− 1.67, − 0.31) variability groups, with the lowest group as the reference. Similarly, Yan et al [29] explored glycaemic variability and the risk of diabetes kidney disease. They found that higher glycaemic variability defined using three methods (HbA1c-SD, HbA1c-AUC, and a HbA1c variability score) were significantly associated with the development of microalbuminuria.…”