CGM-derived average glucose is more strongly associated with microvascular complications than HbA1c in type 1...

To compare the associations of HbA1c and continuous glucose monitoring (CGM)-derived average glucose with microvascular complications in adults with type 1 diabetes, and to assess the clinical utility and stability of metrics capturing glycation discordance.

Observational assessment of 9023 paired measurements of CGM data (14 days) and HbA1c in 2721 adults with type 1 diabetes. CGM metrics, HbA1c, and markers of discordance between HbA1c and CGM average glucose were associated with prevalent retinopathy (any and proliferative) and microalbuminuria.

HbA1c was higher than expected in older individuals (62 mmol/mol [54-71] age >45 vs. 61 mmol/mol [52-71], p = 0.004) and in women (62 mmol/mol [54-71] vs. 61 mmol/mol [53-71], p < 0.001) despite lower or similar average glucose levels. Fewer than one-third of individuals remain within the same HbA1c-average glucose discordance category over time. HbA1c (p < 0.001), average glucose (p < 0.001), CV glucose (p < 0.001), and socioeconomic deprivation (p = 0.003) were all independently associated with retinopathy risk (with similar results for proliferative retinopathy). Higher glycation was associated with a lower likelihood of prevalent retinopathy (p < 0.001).

CGM-derived average glucose appears superior to HbA1c as a marker of prevalent microvascular complications. These data challenge the high-glycator hypothesis and also suggest glucose variability may be an independent risk marker for microvascular disease.