title: The association between diabetes and dermal microvascular dysfunction non-invasively assessed by laser Doppler with local thermal hyperemia: a systematic review with meta-analysis.
abstract: Diabetes and cardiovascular disease develop in concert with metabolic abnormalities mirroring and causing changes in the vasculature, particularly the microcirculation. The microcirculation can be affected in different parts of the body of which the skin is the most easily accessible tissue.
  
  
  
  The association between diabetes and dermal microvascular dysfunction has been investigated in observational studies. However, the strength of the association is unknown. Therefore we conducted a systematic review with meta-analysis on the association between diabetes and dermal microvascular dysfunction as assessed by laser Doppler/laser speckle contrast imaging with local thermal hyperaemia as non-invasive indicator of microvascular functionality.
  
  
  
  PubMed and Ovid were  systematically searched for eligible studies through March 2015. During the first selection, studies were included if they were performed in humans and were related to diabetes or glucose metabolism disorders and to dermal microcirculation. During the second step we selected studies based on the measurement technique, measurement location (arm or leg) and the inclusion of a healthy control group. A random effects model was used with the standardised mean difference as outcome measure. Calculations and imputation of data were done according to the Cochrane Handbook.
  
  
  
  Of the 1445 studies found in the first search, thirteen cross-sectional studies were included in the meta-analysis, comprising a total of 857 subjects. Resting blood flow was similar between healthy control subjects and diabetes patients. In contrast, the microvascular response to local skin heating was reduced in diabetic patients compared to healthy control subjects [pooled effect of -0.78 standardised mean difference (95% CI -1.06, -0.51)]. This effect is considered large according to Cohen's effect size definition. The variability in effect size was high (heterogeneity 69%, p < 0.0001). However, subgroup analysis revealed no difference between the type and duration of diabetes and other health related factors, indicating that diabetes per se causes the microvascular dysfunction.
  
  
  
  Our meta-analysis shows that diabetes is associated with a large reduction of dermal microvascular function in diabetic patients. The local thermal hyperaemia methodology may become a valuable non-invasive tool for diagnosis and assessing progress of diabetes-related microvascular complications, but standardisation of the technique and quality of study conduct is urgently required.
authors.affiliation: Unilever Research and Development, Vlaardingen, Olivier van Noortlaan 120, PO Box 114, 3130 AC, Vlaardingen, The Netherlands. dagmar.fuchs@unilever.com.
authors.forename: Dagmar
authors.identifier: 0000-0001-5799-4681
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Unilever Research and Development, Vlaardingen, Olivier van Noortlaan 120, PO Box 114, 3130 AC, Vlaardingen, The Netherlands.|Faculty of Earth and Life Sciences, Free University Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Pepijn P
authors.initials: PP
authors.lastname: Dupon
authors.affiliation: Faculty of Earth and Life Sciences, Free University Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Schaap
authors.affiliation: Unilever Research and Development, Vlaardingen, Olivier van Noortlaan 120, PO Box 114, 3130 AC, Vlaardingen, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Draijer
mesh_terms: D048909:Diabetes Complications / Q000453:epidemiology / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000503:physiopathology*; D006358:Hot Temperature; D006801:Humans; D006940:Hyperemia / Q000453:epidemiology / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008833:Microcirculation / Q000502:physiology; D055806:Microvessels / Q000503:physiopathology*; D064887:Observational Studies as Topic / Q000379:methods; D012867:Skin / Q000098:blood supply* / Q000503:physiopathology*
keywords: Laser Doppler flowmetry; Laser speckle contrast imaging; Microcirculation; Morphology; Skin perfusion; Vasodilation