Haemoglobin A1c variability is a strong, independent predictor of all‐cause mortality in patients with type 2 diabetes

Abstract

The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.

Effect of mean HbA1c on the association of HbA1c variability and all‐cause mortality in patients with type 2 diabetes

“…characteristics have been reported as associated with mortality and cardiovascular disease. [30][31][32] The association of HbA1c variability with all-cause mortality in this study is consistent with most previous results 7,18,21,[26][27][28][29] ; however, one study did not find such an association. 25 The mechanism underlying this association remains unclear.…”

Beyond HbA1c, second take

“…The standard deviation of HbA1c over time correlates with nephropathy, retinopathy, and cardiovascular events in people with type 1 diabetes, and with nephropathy, foot ulceration, and mortality in people with type 2 diabetes . The relationship between HbA1c variability and mortality is independent of mean HbA1c . A similar relationship was observed between mortality and the coefficient of variability of the fasting glucose in a population of people with diabetes .…”

Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

“…Fifth, the observational design makes causal interpretation impossible. Sixth, there are potential methodological limitations, which have been extensively addressed in previous RIACE reports [13][14][15][16][17][18][19].…”

“…The vital status of study subjects on 31 October 2015 was verified by interrogating the Italian Health Card database (http://sistemats1.sanita.finanze.it/wps/portal/), which provides updated and reliable information on all current Italian residents [14].…”

“…HbA 1c was measured by high-performance liquid chromatography (HPLC) using Diabetes Control and Complications Trial (DCCT)-aligned methods; triglycerides and total and high-density lipoprotein (HDL) cholesterol were determined in fasting blood samples by colorimetric enzymatic methods; non-HDL cholesterol was calculated by the formula: total cholesterol-HDL cholesterol; and low-density lipoprotein (LDL) cholesterol was calculated by the Friedewald formula. HbA 1c variability was calculated for each patient as the intra-individual standard deviation (HbA 1c -SD) of 3-to-5 (4.52 ± 0.76) HbA 1c values obtained in 8252 individuals from 9 centres during the 2-year period preceding recruitment, including the enrolment visit [14].…”