Utility of Contrast-Enhanced Ultrasound for the Assessment of Skeletal Muscle Perfusion in Diabetes Mellitus: A Meta-Analysis

Abstract

BACKGROUND This study evaluated the effectiveness of contrast-enhanced ultrasonography for the assessment of skeletal muscle perfusion in diabetes mellites. MATERIAL AND METHODS Electronic databases (Embase, Google Scholar, Ovid, and PubMed) were searched for required articles, and studies were selected by following pre-determined eligibility criteria. Meta-analyses of mean differences or standardized mean differences (SMD) were performed to evaluate the significance of difference in contrast-enhanced ultrasonography measured muscle perfusion indices between patients with diabetes and healthy individuals or between basal and final values of perfusion indices after insulin manipulation or physical exercise in patients with diabetes or healthy individuals. RESULTS There were 15 studies included, with 279 patients with diabetes and 230 healthy individuals in total. The age of the study patients with diabetes mellitus was 55.8 years (95% CI: 49.6 years, 61.9 years) and these patients had disease for 11.4 years (95% CI: 7.7 years, 15.1 years). The percentage of males in group of patients with diabetes was 66% (95% CI: 49%, 84%), body mass index was 29.4 kg/m² (95% CI: 26.5 kg/m², 32.3 kg/m²), hemoglobin A1c was 7.3% (95% CI: 6.7%, 7.9%), and fasting plasma glucose was 149 kg/m² (95% CI: 118 kg/m², 179 kg/m²). Time to peak intensity after provocation was significantly higher in patients with diabetes than in healthy individuals (SMD 1.18 [95% CI: 0.60, 1.76]; P<0.00001). In patients with diabetes, insulin administration did not improve contrast-enhanced ultrasonography measured muscle perfusion indices but exercise improved muscle perfusion but at a level that was statistically non-significant (SMD between basal and post-exercise values (1.03 [95% CI: -0.14, 2.20]; P=0.08). In healthy individuals, lipids in addition to insulin administration was associated with significantly reduced blood volume and blood flow. CONCLUSIONS Our review showed that the use of contrast-enhanced ultrasonography showed that diabetes mellitus was associated with altered muscle perfusion in which insulin-mediated metabolic changes played an important role.

Figure 1

A flowchart of study screening and selection process.

Figure 2

A forest graph showing the outcomes of a meta-analysis of standardized mean difference between patients with diabetes and healthy individuals in CEU measured muscle perfusion indices. In study identities abbreviations are as follows. BF – blood flow; FR – flow reserve; Exer – exercise; LV – large vessel; SV – small vessel; TAPV – time average peak velocity.

Figure 3

A forest graph showing the outcomes of a meta-analysis of standardized mean difference between basal and post intervention values of muscle perfusion indices in patients with diabetes. In study identities abbreviations are as follows. BABF – brachial artery blood flow; MBF – microvascular blood flow; MBV – microvascular blood volume; MFV – microvascular flow velocity.

Figure 4

A forest graph showing the outcomes of a meta-analysis of standardized mean difference in mean changes in muscle perfusion indices between insulin and insulin-lipid infusion in healthy individuals. In insulin-lipid group, insulin administration was followed by lipids administration to observe changes in muscle perfusion whereas in insulin-saline group changes were observed after insulin administration only.