medwireNews: Higher daily glucose variability (GV) is associated with greater aortic stiffness irrespective of average glucose levels, indicate findings from The Maastricht Study.
“[T]his study further underscores the pathophysiological relevance of daily GV, irrespective of mean glycaemia, in the context of macrovascular complications,” say Coen Stehouwer and colleagues from Maastricht University in the Netherlands.
The team evaluated cross-sectional associations between GV and arterial measures in 853 individuals comprising “the complete spectrum of daily GV,” including those with normal glucose metabolism, prediabetes, type 2 diabetes and type 1 diabetes, who had undergone continuous glucose monitoring (CGM) for at least 48 hours.
As reported in Diabetologia, multiple linear regression analysis showed that the standard deviation of glucose levels as measured with CGM (SDCGM) was significantly associated with carotid–femoral pulse wave velocity (cf-PWV), the gold-standard measure of aortic stiffness. Specifically, each 1 mmol/L increase in SDCGM was associated with a significant 0.413 m/s increase in cf-PWV after adjustment for variables including demographics, cardiovascular risk factors, and medication use.
This association was attenuated, and no longer statistically significant, after additional adjustment for CGM-assessed mean sensor glucose levels, but Stehouwer et al note that the regression coefficient per 1 mmol/L SDCGM in this analysis was not significantly lower than that in the main analysis (0.270 vs 0.413 m/s).
The researchers then used ridge regression analysis to account for multicollinearity and better assess the individual impact of GV and average glucose levels. They found that the strength of the fully adjusted association between SDCGM and cf-PWV was similar to that between mean sensor glucose levels and cf-PWV, with regression coefficients of 0.065 and 0.059, respectively, suggesting that the two variables have “an equivalent pathophysiological relevance to aortic stiffness.”
The team explains that the observed magnitude of increase in aortic stiffness per 1 mmol/L SDCGM increase in the fully adjusted analysis “corresponds with 3–4 years of vascular ageing.” When the study participants were divided into tertiles according to SDCGM, there was a 0.8 mmol/L difference between the first and third tertiles, which Stehouwer et al say “can be translated to a 2- or 3-year vascular ageing difference.”
In accordance with the SDCGM results, Stehouwer and team also report that CGM-assessed coefficient of variation (CVCGM), a measure of GV “that is intrinsically adjusted for mean glycaemia,” and the percentage of time spent in the glucose range of 3.9–10.0 mmol/L (TIRCGM; 70–180 mg/dL), were both significantly associated with cf-PWV in fully adjusted models.
“If corroborated in prospective studies, these results support the development of therapeutic agents that target both daily glucose variability and TIRCGM to prevent [cardiovascular disease],” write the investigators.
They note, however, that “consistent associations were not observed” between the various indicators of GV and other arterial measures, including ankle–brachial index, carotid distensibility coefficient, carotid intima–media thickness, and circumferential wall stress.
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