Associations of serum low-density lipoprotein and systolic blood pressure levels with type 2 diabetic patients with and without peripheral neuropathy: systemic review, meta-analysis and meta-regression analysis of observational studies

Abstract

Background: Compositional abnormalities in lipoproteins and cardiovascular risk factors play an important role in the progression of diabetic peripheral neuropathy (DPN). This systematic review aimed to estimate the predicting value of low-density lipoprotein (LDL) and systolic blood pressure (SBP) level in type-2 diabetes mellitus (T2DM) patients with and without peripheral neuropathy. We also tried to determine whether LDL and SBP are associated with an increased collision risk of DPN.

Methods: A systematic search was conducted for eligible publications which explored the LDL and SBP level in T2DM patients with and without peripheral neuropathy. The quality of the included studies was assessed by the QUADAS-2 tool. The standardized mean difference (SMD) with 95% CI of LDL and SBP level were pooled to assess the correlation between LDL and SBP level with DPN. We performed random effects meta-regression analyses to investigate factors associated with an increased collision risk of DPN.

Results: There was a significant association between LDL and SBP with poor prognosis of DPN in those included studies (I₂ = 88.1% and I₂ = 84.9%, respectively, Both P < 0.001). European T2DM patients have higher serum level of LDL in compare with the European DPN patients (SMD = 0.16, 95% CI: - 0.06 - 0.38; P < 0.001). SBP level was associated with a 2.6-fold decrease in non-DPN patients of T2DM (SMD = - 2.63, 95% CI: - 4.00 - -1.27, P < 0.001). Old age European T2DM patients have significantly high risk for diabetes drivers. Furthermore, the results of the case-control study design model are more precise to show the accuracy of SBP in Asian T2DM patients.

Conclusion: Our finding supports the LDL and SBP status could be associated with increased risk of peripheral neuropathy in T2DM patients.

Keywords: Diabetic peripheral neuropathy; Low-density lipoprotein; Meta-analysis; Meta-regression; Systolic blood pressure; Type 2 diabetes.

Fig. 1

PRISMA diagram for selection of studies (n = number of studies)

Fig. 2

Forest plot of the association between serum LDL level and type 2 diabetic peripheral neuropathy. The differences between DPN and non-DPN groups calculated with standardized mean difference (SMD) with 95% confidence intervals (CIs) in the random effect model

Fig. 3

Summary receiver operating characteristic curve for serum LDL level and subgroup analysis based on race (a) and study design (b). Weights are from random effects analysis

Fig. 4

Forest plot of the association between SBP level and type 2 diabetic peripheral neuropathy. These plots show the prognostics accuracy of SBP for all objective response analysis. The differences between DPN and non-DPN groups calculated with standardized mean difference (SMD) with 95% confidence intervals (CIs) in the random effect model

Fig. 5

Sub group analysis to evaluation the difference of SBP level between DPN and non-DPN in patients with T2DM based of different race (a) and study design (b). Weights are from random effects analysis

Fig. 6

Meta regression results. Meta regression analysis for LDL based on age of participants (a) and year of publication (b) is in compare with meta-regression analysis for SBP based on age of participants (c) and year of publication (d). The size of each square is proportional to the percentage weight that each study contributed to the standardized mean difference (SDM) ratio. Weights are from random effects analysis

Fig. 7

Contour-enhanced funnel plots for the detection of a publication bias of the LDL (a) and SBP (b). All enrolled 16 studies represent by each point for the specified association, individually. The size of each circle is proportional to the percentage weight that each study contributed to the standardized mean difference (SDM). These plots indicate that some studies were in significant areas where P < 0.01 (solid lines). Solid triangles refer to included studies and X’s refer to filled studies. The vertical axis represents standard error of logarithmic HR and the horizontal axis represents the SDM limits. CIs, confidence intervals; HR, hazard ratio