Association between visit‐to‐visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes

Abstract

Aim To investigate the association between visit‐to‐visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes. Materials and methods We performed a retrospective cohort study of 29 260 patients with at least four HbA1c measurements obtained within 2 years of their first diagnosis of type 2 diabetes. Different HbA1c variability markers were calculated, including the standard deviation (SD), coefficient of variation (CV) and adjusted SD. Cox proportional hazards regression models were used to estimate the association of these HbA1c variability markers with incident cardiovascular disease. Results During a mean follow‐up of 4.18 years, a total of 3746 incident cardiovascular disease cases were diagnosed. Multivariate‐adjusted hazard ratios for cardiovascular disease across the first, second, third and fourth quartiles of HbA1c SD values were 1.00, 1.30 (95% confidence interval [CI] 1.18‐1.42), 1.40 (95% CI 1.26‐1.55) and 1.59 (95% CI 1.41‐1.77) (P for trend <.001), respectively. When we utilized HbA1c CV and adjusted HbA1c SD values as exposures, similar positive associations were observed. HbA1c variability was also associated with the risk of first and recurrent severe hypoglycaemic events. A mediating effect of severe hypoglycaemia was observed between HbA1c variability and incident cardiovascular disease. Conclusions Large visit‐to‐visit HbA1c variability is associated with an increased risk of cardiovascular disease in patients with type 2 diabetes. Severe hypoglycaemia may mediate the association between HbA1c variability and incident cardiovascular disease.

The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study

“…Previous papers on “variability” have used various indices to evaluate their variability. SD has been used to evaluate the glycemic, blood pressure, and fasting TG variability ( 19 , 20 , 32 , 33 ) ( 34 , 35 ); the Adj-SD has also been used to evaluate the glycemic and fasting TG variability with adjusting for the number of measurements ( 19 , 21 , 22 , 36 ); and the MMD has been used to evaluate the glycemic and blood pressure variability ( 23 , 24 , 37 , 38 ). Our study suggested that the SD and Adj-SD might be more reliable than MMD, but MMD is calculated more easily than the other two.…”

Glycemic control is not related to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes

“…Blood glycated hemoglobin (HbA 1c ), reflecting blood glucose control during a time span of one to two months, was measured using standardized assays in a central laboratory (Medix Laboratories, Espoo Finland) [12]. Three or more HbA 1c values over the course of ten years before the visit (median count 16, IQR [10][11][12][13][14][15][16][17][18][19][20][21][22][23] were obtained in order to calculate overall mean HbA 1c (HbA 1c -mean overall ) for each individual to better delineate long-term glucose control. These values were collected from local laboratories using standardized methods (HPLC) with a normal range of 4-6%.…”

Long-term glycemic variability and risk of stroke in patients with diabetes: a meta-analysis

“…Although no consensus has been reached regarding the standard definition or measuring methods for glycemic variability, coefficient of variation (CV) or standard deviation (SD) of visit-to-visit fasting plasma glucose (FPG) or HbA1c have been mostly applied for measuring of long-term glycemic variability in previous studies [ 13 , 14 ]. Interestingly, previous studies evaluating the association between glycemic variability and stroke in people with diabetes showed inconsistent results [ 15 – 21 ]. Some studies showed that higher glycemic variability may be associated with higher risk of stroke [ 15 , 17 , 19 , 21 ], while other studies did not [ 16 , 18 , 20 ].…”

“…Interestingly, previous studies evaluating the association between glycemic variability and stroke in people with diabetes showed inconsistent results [ 15 – 21 ]. Some studies showed that higher glycemic variability may be associated with higher risk of stroke [ 15 , 17 , 19 , 21 ], while other studies did not [ 16 , 18 , 20 ]. Moreover, different parameters for long-term glycemic variability were applied among these studies, three with FPG-CV [ 15 , 17 , 19 ], two with FPG-SD [ 17 , 19 ], four with HbA1c-CV [ 18 – 21 ], and the other four with [ 16 , 18 , 19 , 21 ].…”

“…Some studies showed that higher glycemic variability may be associated with higher risk of stroke [ 15 , 17 , 19 , 21 ], while other studies did not [ 16 , 18 , 20 ]. Moreover, different parameters for long-term glycemic variability were applied among these studies, three with FPG-CV [ 15 , 17 , 19 ], two with FPG-SD [ 17 , 19 ], four with HbA1c-CV [ 18 – 21 ], and the other four with [ 16 , 18 , 19 , 21 ]. It remains unknown whether the difference in parameters used may affect the association between long-term glycemic variability and stroke.…”