Abstract
IntroductionNeuregulin 4 (Nrg4) was proven as a brown fat-enriched secreted factor that can regulate glucose and lipid metabolism. However, the association between circulating Nrg4 levels and diabetes mellitus (DM) in human remains unclear. We conducted a meta-analysis to investigate association of circulating Nrg4 with DM.MethodsObservational studies comparing circulating Nrg4 levels in diabetes patients and health controls were included. Circulating Nrg4, correlation coefficients of clinical indices and circulating Nrg4 were pooled by meta-analysis.ResultsSeven studies were included. The pooled results indicated there were no significant difference in the circulating Nrg4 between diabetes patients and controls (SMD = 0.18, 95%CI = -0.06 to 0.42, P = 0.143). However, diabetes patients had higher circulating Nrg4 than their controls in cross-sectional studies (SMD = 0.55, 95%CI = 0.36 to 0.73, P<0.001). None of the renal function and metabolic syndrome markers were correlated with circulating Nrg4, whereas the HbA1c and BMI were positively correlated (rs = 0.09, 95%CI = 0.03 to 0.16, P = 0.005; rs = 0.20, 95%CI = 0.07 to 0.34, P = 0.003; respectively).ConclusionOur findings suggested circulating Nrg4 may play a role in in the development of DM in cross-sectional studies and circulating Nrg4 might be associated with imbalance in glucose metabolism and obesity.
Highlights
Neuregulin 4 (Nrg4) was proven as a brown fat-enriched secreted factor that can regulate glucose and lipid metabolism
The pooled results indicated there were no significant difference in the circulating Nrg4 between diabetes patients and controls (SMD = 0.18, 95%confidence intervals (CIs) = -0.06 to 0.42, P = 0.143)
None of the renal function and metabolic syndrome markers were correlated with circulating Nrg4, whereas the hemoglobin A1c (HbA1c) and body mass index (BMI) were positively correlated
Summary
Observational studies comparing circulating Nrg levels in diabetes patients and health controls were included. Circulating Nrg, correlation coefficients of clinical indices and circulating Nrg were pooled by meta-analysis. We selected only English-language, and the reference lists of identified publications were hand-examined, and the grey literature or ongoing relevant studies were searched on http://www.opengrey.eu/ and http://www.ntis.gov/. Cross-sectional studies and case control studies comparing circulating Nrg levels in diabetes patients and health controls were included. The primary outcome was the association between circulating Nrg levels and DM. The second outcome was correlation coefficients between circulating Nrg levels and the measured clinical indices in subjects with DM. The clinical indices include DM markers (fasting plasma glucose (FPG); HOMA-IR, hemoglobin A1c (HbA1c)), renal function markers (estimated glomerular filtration rate (eGFR), creatinine), metabolic syndrome markers (systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), total cholesterol (TC)), obesity markers (body mass index (BMI), waist circumference (WC)).
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