Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Jan 12;11(1):499.
doi: 10.1038/s41598-020-79276-0.

A systematic review and meta-analysis of the serum lipid profile in prediction of diabetic neuropathy

Zixin Cai  1 , Yan Yang  1 , Jingjing Zhang  2
Affiliations
Meta-Analysis

A systematic review and meta-analysis of the serum lipid profile in prediction of diabetic neuropathy

Zixin Cai et al. Sci Rep. .

Abstract

Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20-0.48 for TG; MD = -0.05, 95% CI: -0.08--0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16-0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10--0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07-0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14-0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08-0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49--0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32--0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28-0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14-0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20-1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02-1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75-0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00-1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow of study selection.
Figure 2
Figure 2
TG levels (A) in people with DN versus those without DN. TG levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum TG levels.
Figure 2
Figure 2
TG levels (A) in people with DN versus those without DN. TG levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum TG levels.
Figure 3
Figure 3
TC levels (A) in people with DN versus those without DN. TC levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum TC levels.
Figure 3
Figure 3
TC levels (A) in people with DN versus those without DN. TC levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum TC levels.
Figure 4
Figure 4
HDL levels (A) in people with DN versus those without DN. HDL levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum HDL levels.
Figure 4
Figure 4
HDL levels (A) in people with DN versus those without DN. HDL levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum HDL levels.
Figure 5
Figure 5
LDL levels (A) in people with DN versus those without DN. LDL levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum LDL levels.
Figure 5
Figure 5
LDL levels (A) in people with DN versus those without DN. LDL levels in the subgroup analysis stratified by the type of diabetes (B) and symptom severity (C). OR (D) for DN in patients according to serum LDL levels.
Figure 6
Figure 6
Publication bias funnel plots of the MD for (A) TG, (B) TC, (C) HDL, and (D) LDL and DN.
Figure 7
Figure 7
Publication bias funnel plots of the OR for (A) TG, (B) TC, (C) HDL, and (D) LDL and DN.
Figure 8
Figure 8
Sensitivity analysis of the pooled MD for (A) TG, (B) TC, (C) HDL, and (D) LDL.
Figure 8
Figure 8
Sensitivity analysis of the pooled MD for (A) TG, (B) TC, (C) HDL, and (D) LDL.
Figure 9
Figure 9
Sensitivity analysis of the pooled OR for (A) TG, (B) TC, (C) HDL, and (D) LDL.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314(20):2172–2181. doi: 10.1001/jama.2015.13611. - DOI - PMC - PubMed
    1. Savettieri G, et al. Prevalence of diabetic neuropathy with somatic symptoms: a door-to-door survey in two Sicilian municipalities. Sicilian Neuro-Epidemiologic Study (SNES) Group. Neurology. 1993;43(6):1115–1120. doi: 10.1212/WNL.43.6.1115. - DOI - PubMed
    1. Bharucha NE, Bharucha AE, Bharucha EP. Prevalence of peripheral neuropathy in the Parsi community of Bombay. Neurology. 1991;41(8):1315–1317. doi: 10.1212/WNL.41.8.1315. - DOI - PubMed
    1. Gregg EW, et al. Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999–2000 national health and nutrition examination survey. Diabetes Care. 2004;27(7):1591–1597. doi: 10.2337/diacare.27.7.1591. - DOI - PubMed
    1. Soedamah-Muthu SS, et al. Relationship between risk factors and mortality in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study (PCS) Diabetes Care. 2008;31(7):1360–1366. doi: 10.2337/dc08-0107. - DOI - PMC - PubMed

Publication types