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Hospitalizations, mortality more likely in type 2 diabetes with high HbA1c variability
Mortality and hospitalization risks are higher for adults with type 2 diabetes who experience larger fluctuations in HbA1c or have very high or very low average HbA1c levels, according to findings published in Diabetes Care.
“Most clinical guidelines suggest the use of individualized patient target levels of HbA1c. Whilst some mention the need for stability in HbA1c, few have any explicit target for variability in HbA1c,” Julia A. Critchley, DPhil, professor of epidemiology at Population Health Research Institute at St. George’s, University of London, told Endocrine Today. “Our study is based on observational data, so we cannot be sure that reducing variability would improve outcomes, and randomized studies are therefore needed. However, it strongly suggests that variability in HbA1c is also associated with poor outcomes and could be used to guide clinical decision making.”
Critchley and colleagues collected data from 2006 to 2009 on HbA1c average, variability and trajectory in 58,832 adults with type 2 diabetes (mean age, 67.7 years; 44.7% women) who were included in the Clinical Practice Research Datalink. Then, using data from 2010 to 2015, the researchers evaluated all-cause mortality and emergency hospitalizations.
Effects of average HbA1c
In fully adjusted models that included adjustments for HbA1c average, trajectory and variability, the researchers observed a 1.14 times greater mortality risk among participants with an average HbA1c of between 3.63% and 6.09% compared with those with the reference level of an average HbA1c greater than 6.09% but no greater than 6.58% (HR = 1.14; 95% CI, 1.05-1.24). In addition, the researchers found a 1.35 times greater mortality risk among participants with an average HbA1c more than 8.88% compared with the reference level (HR = 1.35; 95% CI, 1.24-1.47).
In terms of hospitalizations, the researchers found that those with an average HbA1c between 3.63% and 6.09% had 1.1 times the risk for any hospitalization (HR = 1.1; 95% CI, 1.04-1.15) and 1.11 times the risk for an infection-only hospitalization (HR = 1.11; 95% CI, 1.02-1.21) compared with the reference level. Additionally, participants with an average HbA1c of greater than 7.91% but no greater than 8.88% had 1.12 times the risk for any hospitalization (HR = 1.12; 95% CI, 1.07-1.18), 1.24 times the risk for an infection-only hospitalization (HR = 1.24; 95% CI, 1.14-1.36), 1.2 times the risk for a cardiovascular-only hospitalization (HR = 1.2; 95% CI, 1.12-1.28) and 1.46 times the risk for coronary artery diseases or ischemic stroke hospitalization (HR = 1.46; 95% CI, 1.91-2.37) compared with the reference level. Lastly, those with an average HbA1c of greater than 8.88% had 1.42 times the risk for any hospitalization (HR = 1.42; 95% CI, 1.35-1.5), 1.63 times the risk for an infection-only hospitalization (HR = 1.63; 95% CI, 1.48-1.8), 1.63 times the risk for a CV-only hospitalization (HR = 1.63; 95% CI, 1.51-1.75) and 2.13 times the risk for a CAD or ischemic stroke hospitalization (HR = 2.13; 95% CI, 1.91-2.37) compared with the reference level.
“Our data suggest that for type 2 diabetes patients with lower or moderately raised average HbA1c (< 9% in our cohort), mortality risk might be reduced more by promoting stability than reductions in chronic levels, and even at higher average levels stability remains important,” the researchers wrote.
Effects of HbA1c variability
When looking at HbA1c variability, the researchers found that participants with an HbA1c coefficient of variation greater than 16.64% had 1.93 times the mortality risk compared with those with a coefficient of variation of less than 3.14% (HR = 1.93; 95% CI, 1.72-2.16). In addition, when compared with participants with a coefficient of variation of 3.14% or less, those with a coefficient of variation of greater than 11.4% but no more than 16.64% had 1.71 times the mortality risk (HR = 1.71; 95% CI, 1.53-1.91), participants with a coefficient of variation of greater than 7.33% but no more than 11.4% had 1.51 times the mortality risk (HR = 1.51; 95% CI, 1.38-1.66), and those with a coefficient of variation of greater than 4.71% but no more than 7.33% had 1.32 times the mortality risk (HR = 1.32; 95% CI, 1.21-1.44).
The researchers also found that participants with an HbA1c coefficient of variation of greater than 16.64% had 1.53 times the risk for any hospitalization (HR = 1.53; 95% CI, 1.42-1.64), 1.7 times the risk for an infection-only hospitalization (HR = 1.7; 95% CI, 1.5-1.93) and 1.36 times the risk for CV-only hospitalization (HR = 1.36; 95% CI, 1.22-1.51) compared with those with a coefficient of variation of 3.14% or less. Similarly, the risks of any hospitalization, an infection-only hospitalization and a CV-only hospitalization were all greater for those coefficients of variation that were greater than 3.14% but no more than 16.64% compared with those with a coefficient of variation of 3.14% or less, according to the researchers, who noted that HbA1c variability did not significantly affect the risk of hospitalization for CAD or ischemic stroke.
“HbA1c is routinely measured and recorded in clinical care, but in the UK — and likely elsewhere — variability is not explicitly calculated. However, variability seems to be strongly associated with risk of a poor outcome and can identify patients needing the most support to manage their diabetes,” Critchley said. “Since serial measurements of HbA1c are mainstream in clinical care, variability could easily be calculated and used to guide clinical decisions.” – by Phil Neuffer
For more information:
Julia A. Critchley, DPhil, can be reached at jcritchl@sgul.ac.uk.
Disclosures: The authors report no relevant financial disclosures.
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