Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes

Kang, Yea Eun; Kim, Ji Min; Choung, Sorim; Joung, Kyong Hye; Kim, Hyun Jin; Ku, Bon Jeong

doi:10.1016/j.diabres.2016.04.007

Cited by 42 publications

(53 citation statements)

References 9 publications

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“…However, Nrg‐4 has been reported to play a role in regulating systemic energy balance and glucose and lipid metabolism and in reducing chronic inflammation . Decreased Nrg‐4 levels have been reported to be associated with type 2 diabetes mellitus, obesity, insulin resistance (IR), hyperglycaemia, oxidative stress and inflammation …”

Section: Introductionmentioning

confidence: 99%

“…8,10,11 Decreased Nrg-4 levels have been reported to be associated with type 2 diabetes mellitus, obesity, insulin resistance (IR), hyperglycaemia, oxidative stress and inflammation. [12][13][14][15] Although the mechanisms involved in the development and progression of DMC are different and not fully explained, some common features such as oxidative stress and inflammation are present. Therefore, new predictable factors are needed in the diagnosis of DMC.…”

Section: Introductionmentioning

confidence: 99%

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Is Neuregulin‐4 a predictive marker of microvascular complications in type 2 diabetes mellitus?

Koçak

Aktas

Tel

et al. 2020

Eur J Clin Investigation

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Background and Aims Neuregulin‐4 (Nrg‐4) is a new adipokine released from brown adipose tissue. It plays pivotal role in regulating systemic energy balance, glucose and lipid metabolism and in reducing chronic inflammation. We aimed to investigate the relation between diabetic microvascular complications (DMC) and serum (Nrg‐4) levels in patients with type 2 diabetes mellitus. Methods Patients with type 2 diabetes mellitus were divided into DMC and diabetic patients without microvascular complications (non‐DMC). Nrg‐4 levels of the patients were compared. Results Fifty and 29 patients enrolled to the DMC and non‐DMC groups, respectively. Nrg‐4 was 1.23 (0.02‐5.1) ng/mL and 2.5 (0.21‐6.01) ng/mL in DMC and in non‐DMC groups, respectively (P < .001). In patients with DMC, FPG was 189.5 (89‐446) mg/ dL, whereas it was 128 (95‐278) mg/dL in non‐DMC diabetic patients (P < .001). HbA1c was also significantly higher in the DMC group than in the non‐DMC group (P < .001). Negative correlation was found between Nrg‐4 and FPG (r = −0.231, P = .03), HBA1c (r = −0.312, P = .003) and microalbuminuria (r = −0.277, P = .009). Logistic regression analysis showed a 1‐unit decrease in Nrg‐4 to increase the presence of DMC by 1.9 times. The best cut‐off value of Nrg‐4 was 1.56 ng/mL with 82.1% sensitivity and 64% specificity, in predicting DMC. Conclusion In patients with diabetes, Nrg‐4 levels may be a good predictor of early detection of one or more DMC, as microvascular dysfunction in an organ system is considered to be an initial onset of subclinical systemic damage.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Is Neuregulin‐4 a predictive marker of microvascular complications in type 2 diabetes mellitus?

Koçak

Aktas

Tel

et al. 2020

Eur J Clin Investigation

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“…Nrg4 overexpression in mice controls liver lipogenesis and prevents high‐fat diet‐induced obesity and NAFLD, while Nrg4 deficiency exacerbates hepatic steatosis and insulin resistance. However, this association is challenged by clinical studies in human adults that show that serum Nrg4 levels are lower in patients with NAFLD than in non‐NAFLD controls but higher in patients with type 2 diabetes mellitus than in those without . Therefore, it seems that the association of Nrg4 with metabolic diseases is inconsistent based on available data and more clinical evidence is needed to determine the role of Nrg4 in metabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

Decreased serum neuregulin 4 levels associated with non‐alcoholic fatty liver disease in children with obesity

Wang

Yang

et al. 2018

Clinical Obesity

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Neuregulin 4 (Nrg4), a newly identified adipokine secreted by brown adipose tissue, is hypothesised to play a crucial role in metabolism. The present study aimed to evaluate the association between serum Nrg4 levels and non‐alcoholic fatty liver disease (NAFLD) in children with obesity in China. A total of 123 children with obesity were included in this study. Anthropometric and biochemical parameters were measured in all subjects. NAFLD was diagnosed using ultrasonography. The serum levels of Nrg4, leptin and adiponectin were measured by enzyme‐linked immunosorbent assay. NAFLD was identified in 58 children with obesity (47.2%). Serum Nrg4 levels were significantly lower in the NAFLD group (2.24 [1.20, 3.22] ng/mL) than in the control group (5.50 [2.45, 10.85] ng/mL) (p < 0.001). Serum Nrg4 levels were negatively correlated with most of the anthropometric and biochemical parameters (p < 0.05) but were positively correlated with high‐density lipoprotein cholesterol (p < 0.05). In multiple stepwise regression analyses, serum Nrg4 levels were independently related with WHtR (β = −2.009, p = 0.048) and homeostasis model assessment of insulin resistance (β = −0.524, p = 0.005). Furthermore, a multivariable logistic regression analysis of NAFLD prediction by Nrg4 revealed an odds ratio of 0.129 (95% confidence interval: 0.028–0.587, p < 0.01). The receiver operating characteristic curve analysis of the diagnostic value of using serum Nrg4 levels to differentiate NAFLD in children with obesity showed that the area under the curve was 0.723; the cutoff for serum Nrg4 levels to have diagnostic value for predicting NAFLD in children with obesity was 3.39 ng/mL. Elevated Nrg4 is associated with a decreased risk of NAFLD in children with obesity.

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“…Kang et al have found that there was no significant difference in the serum NRG4 levels when comparing type 2 diabetic patients with non-diabetic patients. Yet, there was a positive correlation between NRG4 levels and FBG, HOMA-IR and triglyceride levels [17]. In contrast, Zhang et al have reported that type 2 diabetic patients were found to have Pearson's correlation analysis was used.…”

Section: Discussionmentioning

confidence: 89%

“…It activates epidermal growth factor receptor (EGFR), also known as erbB receptor, and is synthesized in many tissues, especially in BAT [12,17]. The hypothalamic-pituitary-gonadal axis and the luteinizing hormone-releasing hormone (LHRH) are required for healthy pubertal development [18,19].…”

Section: Discussionmentioning

confidence: 99%

Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A case-control study

Temür

Çalan²,

Akşit³

et al. 2017

Ginekol Pol

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Objectives: Neuregulin 4 (NRG4) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum NRG4 levels and various metabolic parameters in women with PCOS. Material and methods:This cross-sectional study included 40 women with PCOS and 40 age-and BMI-matched controls without PCOS. NRG4, fasting blood glucose (FBG), insulin, hs-CRP, LDL-C, HDL-C, SHBG, DHEA-SO 4 and total-testosterone levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance.Results: Serum NRG4 levels were higher in women with PCOS than in healthy women (24.89 ± 9.32 [ng/mL] vs. 18.98 ± 6.40 [ng/mL], p = 0.002). FBG, LDL-C, HDL-C, LH, SHBG, FAI, DHEA-SO4, insulin, hs-CRP, HOMA-IR and total-testosterone levels were significantly higher in women with PCOS than controls. Circulating NRG4 levels were positively correlated with HOMA-IR, insulin and hs-CRP for both groups. There was a positive correlation between NRG4 and FBG in the PCOS group. HOMA-IR and hs-CRP were associated with NRG4. Conclusion:The high concentration of circulating NRG4 in PCOS may be associated with insulin resistance and low-grade chronic inflammation.

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Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes

Cited by 42 publications

References 9 publications

Is Neuregulin‐4 a predictive marker of microvascular complications in type 2 diabetes mellitus?

Is Neuregulin‐4 a predictive marker of microvascular complications in type 2 diabetes mellitus?

Decreased serum neuregulin 4 levels associated with non‐alcoholic fatty liver disease in children with obesity

Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A case-control study

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