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

F. Casanova, D. D. Adingupu, F. Adams, K. M. Gooding, H. C. Looker, K. Aizawa, F. Dove, S. Elyas, J. J. F. Belch, P. E. Gates, R. C. Littleford, M. Gilchrist, H. M. Colhoun, A. C. Shore, F. Khan (Lead / Corresponding author), W. D. Strain

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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.

Original languageEnglish
Article number114
Pages (from-to)1-11
Number of pages11
JournalCardiovascular Diabetology
Volume16
DOIs
Publication statusPublished - 15 Sep 2017

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Single Nucleotide Polymorphism
Morbidity
Cardiovascular Models
Microcirculation
Hyperglycemia
Type 2 Diabetes Mellitus
Analysis of Variance
Lasers
Cardiovascular Diseases
Guidelines

Keywords

  • Diabetes
  • Cardiovascular disease
  • Microcirculation
  • Glycaemic legacy

Cite this

Casanova, F. ; Adingupu, D. D. ; Adams, F. ; Gooding, K. M. ; Looker, H. C. ; Aizawa, K. ; Dove, F. ; Elyas, S. ; Belch, J. J. F. ; Gates, P. E. ; Littleford, R. C. ; Gilchrist, M. ; Colhoun, H. M. ; Shore, A. C. ; Khan, F. ; Strain, W. D. / The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control. In: Cardiovascular Diabetology. 2017 ; Vol. 16. pp. 1-11.
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title = "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 = "Diabetes, Cardiovascular disease, Microcirculation, Glycaemic legacy",
author = "F. Casanova and Adingupu, {D. D.} and F. Adams and Gooding, {K. M.} and Looker, {H. C.} and K. Aizawa and F. Dove and S. Elyas and Belch, {J. J. F.} and Gates, {P. E.} and Littleford, {R. C.} and M. Gilchrist and Colhoun, {H. M.} and Shore, {A. C.} and F. Khan and Strain, {W. D.}",
note = "This received support from the Innovative Medicines Initiative Joint Undertaking under the Grant Agreement No. 115006; http://www.imi-summit.eu.",
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Casanova, F, Adingupu, DD, Adams, F, Gooding, KM, Looker, HC, Aizawa, K, Dove, F, Elyas, S, Belch, JJF, Gates, PE, Littleford, RC, Gilchrist, M, Colhoun, HM, Shore, AC, Khan, F & Strain, WD 2017, 'The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control', Cardiovascular Diabetology, vol. 16, 114, pp. 1-11. https://doi.org/10.1186/s12933-017-0594-7

The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control. / Casanova, F.; Adingupu, D. D.; Adams, F.; Gooding, K. M.; Looker, H. C.; Aizawa, K.; Dove, F.; Elyas, S.; Belch, J. J. F.; Gates, P. E.; Littleford, R. C.; Gilchrist, M.; Colhoun, H. M.; Shore, A. C.; Khan, F. (Lead / Corresponding author); Strain, W. D.

In: Cardiovascular Diabetology, Vol. 16, 114, 15.09.2017, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control

AU - Casanova, F.

AU - Adingupu, D. D.

AU - Adams, F.

AU - Gooding, K. M.

AU - Looker, H. C.

AU - Aizawa, K.

AU - Dove, F.

AU - Elyas, S.

AU - Belch, J. J. F.

AU - Gates, P. E.

AU - Littleford, R. C.

AU - Gilchrist, M.

AU - Colhoun, H. M.

AU - Shore, A. C.

AU - Khan, F.

AU - Strain, W. D.

N1 - This received support from the Innovative Medicines Initiative Joint Undertaking under the Grant Agreement No. 115006; http://www.imi-summit.eu.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - 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.

AB - 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.

KW - Diabetes

KW - Cardiovascular disease

KW - Microcirculation

KW - Glycaemic legacy

U2 - 10.1186/s12933-017-0594-7

DO - 10.1186/s12933-017-0594-7

M3 - Article

VL - 16

SP - 1

EP - 11

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

M1 - 114

ER -