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The potential role of angiopoietin-like protein-8 in type 2 diabetes mellitus: a possibility for predictive diagnosis and targeted preventive measures?

Abstract

Background

Previous studies showed altered angiopoietin-like protein-8 (ANGPTL-8) circulating levels in type 2 diabetes mellitus (DM). Whether or not the alteration in ANGPTL-8 level can be a predictive maker for increased DM risk remains unclear.

Aim

Investigating possible role of ANGPTL-8 as a risk predictor of type2 DM, in addition to a set of factors likely to affect ANGPTL-8 level.

Methods

One hundred recently diagnosed persons with type 2 DM and 100 sex- and age-matched healthy controls were enrolled. Exclusion criteria included type 1 DM, acute infections, history of chronic kidney disease, malignancy, and blood loss or transfusion. Serum levels of ANGPTL-8, blood pressure, weight, height, glycosylated hemoglobin (HbA1c), fasting blood glucose, cystatin C, lipid profile, liver, and kidney function tests were assessed. The independent relationship between DM and ANGPTL-8 was tested in the unadjusted and multiple-adjusted regression models.

Results

Serum ANGPTL-8 levels showed significant elevation among persons with vs. without DM (p = 0.006), positive correlation with HbA1c (p < 0.001), and negative correlation with estimated GFR (eGFR) (p = 0.003) but no significant correlation to fasting glucose level. In the unadjusted model, patients in the third tertile of ANGPTL-8 had 4 times risk of DM (OR 4.03; 95% CI = 1.37–11.84). Data adjustment for cardiovascular diseases, smoking, body mass index, systolic blood pressure, alanine transaminase (ALT), and low-density lipoprotein (LDL) increased the direct relationship between ANGPTL-8 and DM (OR 6.26; 95% CI = 1.21–32.50). However, the risk significantly decreased after adjustment of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin (OR 2.17; 95% CI = 0.10–49.84).

Conclusion

This study highlights a possible predictive role of ANGPTL-8 in diabetic complications, particularly nephropathy. Larger prognostic studies are needed to validate the cause-effect relationship between ANGPTL-8 and deteriorated kidney functions.

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Acknowledgments

The authors would like to acknowledge the efforts of the medical postgraduate student Mohamed Abd Allah ElKelany, in data collection and entry.

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Authors

Contributions

All authors contributed to the conception of idea, study design, laboratory investigations, interpretation of results, writing and revising the manuscript, providing intellectual content of critical importance to the work described, and final approval of the version to be published. In addition, Dr. Yasmine Amr Issa carried out all laboratory investigations, Dr. Samar Samy Abd ElHafeez was responsible for statistical analysis, and Dr. Noha Gaber Amin executed the recruitment, examination, and data collection of patients. All authors are also accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Yasmine Amr Issa.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Alexandria Faculty of Medicine Ethics of the research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Issa, Y.A., Abd ElHafeez, S.S. & Amin, N.G. The potential role of angiopoietin-like protein-8 in type 2 diabetes mellitus: a possibility for predictive diagnosis and targeted preventive measures?. EPMA Journal 10, 239–248 (2019). https://doi.org/10.1007/s13167-019-00180-3

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Keywords

  • Type 2 diabetes mellitus
  • ANGPTL-8
  • Predictive preventive personalized medicine
  • Renal function
  • Adipokine
  • Hepatokine