Abstract
BackgroundGood glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function.Methods743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging.ResultsPeople with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) −0.096, p = <0.008 and −0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β −0.099; p = 0.006 and −0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (β −0.043; p = 0.3), but not between HbA1c and SNP (β −0.105; p = 0.02).ConclusionsIn those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for “advanced disease” than concomitant CVD, although this requires prospective validation.
Highlights
Whereas cardiovascular disease (CVD) is responsible for the majority of mortality in people with type 2 diabetes mellitus (T2DM), the microvascular complications, such as retinopathy and nephropathy, have the greatest impact on patient’s quality of life [1] and the economic cost of patients’ management [2]
Individuals with T2DM were treated with diet only (19.5%), oral glucose lowering medications only (58.2%), and insulin
The results of this study demonstrate for the first time that the microvascular dysfunction associated with T2DM and CVD are additive
Summary
Whereas cardiovascular disease (CVD) is responsible for the majority of mortality in people with type 2 diabetes mellitus (T2DM), the microvascular complications, such as retinopathy and nephropathy, have the greatest impact on patient’s quality of life [1] and the economic cost of patients’ management [2]. Cardiovascular outcome trials such as LEADER [9] and Sustain-6 [10] have demonstrated a differential benefit on major adverse cardiac events (MACE) in those with pre-existing CVD compared to those at high risk of a cardiovascular event In these studies, participants who were recruited without experiencing a previous event failed to gain any additional benefit from the GLP-1 based therapy, whereas treatment incurred a risk reduction in those who had experienced previous CV events. Participants who were recruited without experiencing a previous event failed to gain any additional benefit from the GLP-1 based therapy, whereas treatment incurred a risk reduction in those who had experienced previous CV events This raises doubts over the equal weight placed on preexisting CVD/co-morbidities and duration of disease when it comes to target setting for glycaemic control. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function
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