The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control

Abstract

Background: Good 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.

Methods: 743 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.

Results: People 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).

Conclusions: In 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.

Keywords: Cardiovascular disease; Diabetes; Glycaemic legacy; Microcirculation.

Fig. 1

Endothelial dependent and independent function (mean ± SD) stratified by recruitment group. As multiple comparisons have been made, a p < 0.008 should be regarded as statistically significant. a Peak endothelial dependent responses to acetylcholine (ACh); b Peak endothelial independent response to sodium nitroprusside (SNP). No DM No CVD: recruited with no evidence of diabetes or overt cardiovascular disease; No DM with CVD: recruited with no evidence of diabetes, but pre-existing cardiovascular disease; DM No CVD: recruited with pre-existing diabetes but no evidence of cardiovascular disease; DM with CVD: recruited with pre-existing diabetes and cardiovascular disease

Fig. 2

Determinants of attenuated microvascular function in those with cardiovascular disease, irrespective of diabetes, combined (mean ± 95% CI). As multiple comparisons have been made, a p < 0.008 should be regarded as statistically significant. a Peak endothelial dependent responses to acetyl choline (ACh) in those with and without pre-existing cardiovascular disease adjusted for age and sex (mean ± CI). b Peak endothelial independent response to sodium nitroprusside (SNP) in those with and without pre-existing cardiovascular disease adjusted for age and sex. c Peak endothelial dependent responses to acetyl choline (ACh) in those with and without pre-existing cardiovascular disease adjusted for age, sex and conventional cardiovascular risk factors (body mass index, mean arterial blood pressure, total cholesterol and smoking status). d Peak endothelial independent response to sodium nitroprusside (SNP) in those with and without pre-existing cardiovascular disease adjusted for age, sex and conventional cardiovascular risk factors (body mass index, mean arterial blood pressure, total cholesterol and smoking status). CVD participants recruited with pre-existing cardiovascular disease; No CVD participants recruited with no clinical history of cardiovascular disease

Fig. 3

Determinants of attenuated microvascular function in those with diabetes (mean ± 95% CI), irrespective of cardiovascular disease status combined. a Peak endothelial dependent responses to acetylcholine (ACh) in those with and without diabetes adjusted for age and sex. b Peak endothelial independent response to sodium nitroprusside (SNP) in those with and without diabetes adjusted for age and sex. c Peak endothelial dependent responses to acetylcholine (ACh) in those with and without diabetes adjusted for age, sex and conventional cardiovascular risk factors (body mass index, mean arterial blood pressure, total cholesterol and smoking status). d Peak endothelial independent response to sodium nitroprusside (SNP) in those with and without diabetes adjusted for age, sex and conventional cardiovascular risk factors (body mass index, mean arterial blood pressure, total cholesterol and smoking status). e Peak endothelial dependent responses to acetylcholine (ACh) in those with and without diabetes adjusted for age, sex, conventional cardiovascular risk factors and HbA₁c. f Peak endothelial independent response to sodium nitroprusside (SNP) in those with and without diabetes adjusted for age, sex, conventional cardiovascular risk factors and HbA₁c. DM participants recruited with diabetes (including those diagnosed during screening); No DM participants recruited with no clinical history of diabetes and no elevated HbA1c at screening