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Intensive treatment associated with high HbA1c variability in type 2 diabetes
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Adults with type 2 diabetes prescribed triple oral therapy or insulin therapy are more than 6 times more likely to have highly variable HbA1c measurements when compared with patients treated with diet alone, independent of baseline HbA1c, according to findings from a case-control study from Scotland.
“The detrimental consequences of high [glycemic] intraday variability have been mapped at a cellular level and are well documented,” Ewan R. Pearson, MBBCh, PhD, professor of diabetic medicine at the University of Dundee, U.K., and colleagues wrote. “The cellular effects of elevated HbA1c variability are unknown, which gives rise to the possibility that two distinct biological processes are occurring. Establishing whether the same patient characteristics are associated with both raised intraday and HbA1c variability is of interest, because the findings could provide an insight into the biological processes responsible for increased HbA1c variability and its associated adverse outcomes.”
Pearson and colleagues analyzed data from 10,130 adults with type 2 diabetes and at least four HbA1c readings within a 4-year window between January 2010 and January 2014, identified from the Scottish Care Information-Diabetes Collaboration. Glycemic variability was defined by two metrics: standard deviation (SD) and coefficient of variation (CV). Researchers stratified patients as having high HbA1c variability (cases) or low HbA1c variability (controls) for both SD and CV methods. Researchers used logistic regression analyses to determine patient characteristics associated with HbA1c variability.
In preliminary analyses, researchers observed a positive association between mean HbA1c level and variability; data were then stratified into two groups based on mean HbA1c level (low mean, < 7%; and high mean, 7%).
Within the cohort, 2,709 patients had low HbA1c variability, of which 2,709 had a low mean HbA1c and 669 had a high mean HbA1c; 3,376 patients had high HbA1c variability, of which 348 had a low mean HbA1c and 3,028 had a high mean HbA1c.
Researchers found that, across both HbA1c groups and variability metrics, odds of higher HbA1c variability were greater in patients prescribed triple therapy or insulin therapy compared with those prescribed monotherapy or dual therapy. Compared with patients treated with diet alone, those in the low mean HbA1c group treated with triple therapy or insulin therapy were more than 6 times more likely to have highly variable HbA1c (OR = 6.64; 95% CI, 3.72-11.86). Patients in the high mean HbA1c group also saw increased risk for HbA1c variability with triple or insulin therapy compared with those treated with diet, though not as marked (OR = 3.15; 95% CI, 2.21-4.47).
High HbA1c variability was also associated with age; patients aged 55 years and younger were more than twice as likely to have high variability compared with those aged at least 75 years, according to researchers. Additionally, male sex, reduced HDL-cholesterol and increased BMI were all independently associated with raised visit-to-visit glycemic variability. Results persisted in sensitivity analyses removing patients with low mean HbA1c (< 6.5%) and those with high mean HbA1c (at least 9%).
“The treatment prescribed to a person with type 2 diabetes was found to be strongly associated with their risk of having highly variable HbA1c,” the researchers wrote. “This is particularly striking in the stratum with mean HbA1c < 7%. In this group, the participants who were intensively treated, with triple oral therapy or insulin, to achieve this target had a more than 6-fold increased risk of having highly variable HbA1c. Within this group, greater variability again was seen in those on insulin compared with triple oral therapy, although the numbers were small.”
The researchers noted that the results reflect findings in the ACCORD study, which showed that aggressive treatment initiated to achieve an HbA1c of 6.5% or less resulted in increased mortality compared with a less aggressive HbA1c target.
“Our findings support the rationale in the guidelines that emerged after ACCORD, that there should be a low HbA1c target [for] those early in the disease process and a less aggressive target once treatment has intensified.” – by Regina Schaffer
Disclosure: The authors report no relevant financial disclosures.
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