A1c Swings Tied to More Diabetes Complications Long Term

Marlene Busko

October 02, 2019

BARCELONA, Spain — Patients with newly diagnosed type 2 diabetes who had highly variable A1c levels between visits were more likely to have macro- and microvascular complications of diabetes in long-term follow-up, a study shows.

The heightened risk of 10 adverse outcomes — major adverse cardiovascular events (MACE), all-cause mortality, cardiovascular death, coronary artery disease, ischemic stroke, heart failure, diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot ulcer, and chronic kidney disease — was independent of the patients' baseline characteristics or average A1c levels.

Lead author Sheyu Li, MD, West China Hospital, Sichuan University, Chengdu, China, and University of Dundee, UK, presented this retrospective study of patients in the Scottish Care Information — Diabetes Collaboration (SCI-DC) as a poster and during a press briefing at the European Association for the Study of Diabetes (EASD) 2019 Annual Meeting.

Those With Variable A1c Scores Fare Worse; Can This Be Tackled?

Some patients have highly variable A1c, and others have stable A1c from visit to visit.

Other research has described how variability in A1c levels is associated with worse outcomes, senior author Ewan Pearson, MB BChir, PhD, professor of diabetic medicine, University of Dundee, UK, acknowledged to Medscape Medical News.

But "what is new here is...we use the newer A1c variability score, and [we] followed a lifetime trajectory from new diagnosis [of type 2 diabetes] to the [adverse] event."

"We can say that patients with variable A1c levels have worse outcomes," he explained, "but so far we can't say why...and what you can do about it."  

A previous study, the researchers note, suggests that "frequent fluctuation of A1c can be driven by multiple clinical factors, including variation in diet and lifestyle, changing to different antidiabetic drugs, and/or withdrawing of antidiabetic treatment, and general healthcare quality" (Diabetes Care. 2019;42:514-519).

Some patients may also be noncompliant with therapy, but "the biggest thing will be people who eat, put on weight, and diet" in a yo-yo pattern, Pearson speculated.

However, "at this stage, it is important to emphasize that we can't say that the adverse outcomes are definitively caused by the increased variability in A1c, and therefore we cannot yet be sure that reducing A1c variability will reduce that risk," the researchers caution.

Nevertheless, Pearson said, "I'm very much aware now when I see patients, I look at their A1c pattern" and treat them differently if they have a stable versus a variable pattern.

However, he acknowledged: "You can't really [globally] change [clinical] practice until you’ve established that there's something you can do that will result in improved outcomes."

Does Visit-to-Visit Variation in A1c Matter?

Li said the current study aimed to shed light on the question: "Is achieving the A1c target everything in the management of diabetes?"

Researchers analyzed data from 21,352 patients in Tayside and Fife in Scotland, who were part of the SCI-DC.

Patients were 40 years or older when they were diagnosed with diabetes (to limit the inclusion of those with type 1 diabetes), had baseline data, and had at least 5 and up to 20 or more A1c measures at different visits.

The A1c variability score was defined as the percentage of changes in A1c that were more than 0.5%.

Researchers classified the variability scores into five ranges from 0 to ≤ 20% (lowest) to 80% to ≤ 100% (highest).

Compared to patients with the lowest A1c variability scores, those with the highest A1c variability scores had a 2.4 times increased risk of all-cause mortality, and a similar risk of MACE and of cardiovascular death — even after adjusting for baseline differences and average A1c levels over time.

Patients with the greatest variability in A1c levels also had a 2.6 times increased risk of coronary artery disease, doubled the risk of ischemic stroke, and triple the risk of heart failure.

And they had a much greater risk of other complications of diabetes: a 7.4 times increased risk of retinopathy, triple the risk of peripheral neuropathy, a 5.2 times increased risk of foot ulcer, and a 3.5 times increased risk of new-onset chronic kidney disease.

Patients who had higher A1c variability tended to be younger and male, Li noted, with a lower socioeconomic status and higher baseline A1c levels. These findings are consistent with a previous study by the group in which higher A1c variability was associated with age, sex, body mass index, social deprivation, and treatment patterns (Diabet Med. 2018;35:262-269). "This difference may explain some of the increased risk in those with high variability in A1c" in the current study, the researchers suggest.

This previous study looked at day-to-day variation in A1c, as opposed to within-day glycemic control, and few people in this study had continuous glucose monitors, Li stressed.

Li was supported by the International Visiting Program for Excellent Young Scholars of SCU. The authors have reported no relevant financial disclosures.

EASD 2019 Annual Meeting. Presented September 19, 2019. Abstract 1190.

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