Widely-accepted thought in diabetes management today is that, the more ups and downs patients have in their glucose levels, the more these fluctuations contribute to complications such as diabetic retinopathy. However a new study of a representative cohort indicates no independent association between a drop in HbA1c with onset or worsening of retinopathy.

The observational study at University of Edinburgh clinics, Royal Infirmary of Edinburgh, United Kingdom, examined a cohort of 541 individuals with type 1 diabetes who began an innovative interstitial glucose monitoring system. Flash monitoring pairs a subcutaneous upper arm sensor with a reading device — such as the patient’s cell phone — that is able to scan glucose trends from the past 24 hours. 

During the average follow-up period of 615 days, researchers found that new onset of mild retinopathy was associated with the length of time subjects had been diagnosed with diabetes (24 years, 14-33, vs 14 years, 8-30; P <.001). Onset was also associated with higher HbA1c at baseline (65 mmol/mol, 57-73, vs 61 mmol/mol, 54-68; P =.014). However, new retinopathy was not significantly associated with change in HbA1c (P =.176).

In regard to worsening retinopathy at interim follow-up, an association was found with higher baseline HbA1c as well (69 mmol/mol, 48-81, vs 63 mmol/mol, 55-71; P =.010). In addition, lower frequency of retinopathy at baseline was associated with worsening retinopathy (18.6% vs 54.8%; P <.001).


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“We have demonstrated that HbA1c lowering, in the context of flash monitoring commencement, is not independently predictive of clinically important changes in diabetic eye disease in the short term,” the researchers wrote. “HbA1c prior to commencement of flash monitoring, as well as diabetes duration and pre-existing retinopathy were all independently associated with progression of eye disease.”

The current study contrasts with findings of the Diabetes Control and Complications Trial (DCCT), for which subjects in an intensive glycemic management group faced early worsening of diabetic retinopathy before experiencing meaningful and long-term benefits. Edinburgh researchers noted that management of risk factors and options for treatment have evolved considerably since the DCCT was conducted in 1983 to 1993. 

A limitation of the observational study was non-uniform timing of HbA1c screening with the eye assessment visit — and, for some subjects, delayed assessment might have caused instances of early worsening to go unnoticed. Also, the cohort size may have been too small or the disease events incidentally fewer. “However, in multivariate analysis of the composite end point (macular laser, PRP, or anti-VEGF therapy), new development of retinopathy and worsening of retinopathy, the absence of association was clear, consistent, and not close to approaching statistical significance,” the investigators wrote.

Moderating the effects of hypoglycemia and glucose variability are emerging topics for study as glucose monitoring and insulin delivery further develop into continuous and looped systems, the researchers added.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.  

Reference

Al-Dalla Ali M, Stimson RH, Dover AR, et al. HbA1c reduction following flash monitoring commencement is not independently associated with adverse diabetic eye disease outcomes in type 1 diabetes. BMJ Open Diabetes Research & Care. 2020;8:e001668. doi: 10.1136/bmjdrc-2020-001668