ANGPTL4: A Predictive Marker for Diabetic Nephropathy

Background. ANGPTL4 is a glycoprotein that is involved in regulating triglyceride metabolism by inhibiting LPL activity under fasting conditions. Additionally, ANGPTL4 has been suggested as a link between hypertriglyceridemia and albuminuria in the nephrotic syndrome. In this study, we examined leve...

Full description

Saved in:
Bibliographic Details
Main Authors: Eman Al Shawaf, Mohamed Abu-Farha, Sriraman Devarajan, Zahra Alsairafi, Irina Al-Khairi, Preethi Cherian, Hamad Ali, Aditi Mathur, Fahd Al-Mulla, Abdulnabi Al Attar, Jehad Abubaker
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2019/4943191
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832554476213370880
author Eman Al Shawaf
Mohamed Abu-Farha
Sriraman Devarajan
Zahra Alsairafi
Irina Al-Khairi
Preethi Cherian
Hamad Ali
Aditi Mathur
Fahd Al-Mulla
Abdulnabi Al Attar
Jehad Abubaker
author_facet Eman Al Shawaf
Mohamed Abu-Farha
Sriraman Devarajan
Zahra Alsairafi
Irina Al-Khairi
Preethi Cherian
Hamad Ali
Aditi Mathur
Fahd Al-Mulla
Abdulnabi Al Attar
Jehad Abubaker
author_sort Eman Al Shawaf
collection DOAJ
description Background. ANGPTL4 is a glycoprotein that is involved in regulating triglyceride metabolism by inhibiting LPL activity under fasting conditions. Additionally, ANGPTL4 has been suggested as a link between hypertriglyceridemia and albuminuria in the nephrotic syndrome. In this study, we examined levels of circulating ANGPTL4 in people with diabetic nephropathy (DN) and its association with established DN-associated proteins such as IGFBP1 and IGFBP4. Methods. We quantified circulating ANGPTL4, IGFBP1, IGFBP3, and IGFBP4 in fasting plasma samples of 122 Kuwaiti participants using a multiplexing assay. The study involved 36 controls, as well as 86 people with type 2 diabetes (T2D) including 37 people with normal kidney function and 49 people with DN. Results. ANGPTL4 level was increased in people with DN (241.56±14.1 μg/ml) compared to the control group (178.43±24.09 μg/ml). The increase in ANGPTL4 correlated with clinical parameters of DN including albumin-to-creatinine ratio (r=0.271, P=0.002), serum creatinine (r=0.381, P=0.0001), and eGFR (r=−0.349, P<0.0001). Furthermore, ANGPTL4 correlated positively with both IGFBP1 (r=0.202, P=0.026) and IGFBP4 (r=0.364, P<0.0001). Multiple regression analysis showed increased IGFBP1 and TG as predictors of higher ANGPTL4 in people with DN. In people with T2D, only IGFBP1 acted as a positive predictor of a rise in ANGPTL4. Conclusion. In this study, our data showed a significant increase in circulating ANGPTL4, IGFBP1, and IGFBP4 in patients with DN. The elevation in ANGPTL4 correlated significantly with clinical markers of DN such as ACR, serum creatinine, and eGFR, as well as IGFBP1 and IGFBP4. Altogether, this suggests a potential role for ANGPTL4 in DN perhaps through its role in inhibiting LPL activity and promotes ANGPTL4 as a biochemical marker for the detection of a diabetic kidney disease in patients with T2D.
format Article
id doaj-art-0a64a8dedd404beca28a579e6f8ff6da
institution Kabale University
issn 2314-6745
2314-6753
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Journal of Diabetes Research
spelling doaj-art-0a64a8dedd404beca28a579e6f8ff6da2025-02-03T05:51:19ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/49431914943191ANGPTL4: A Predictive Marker for Diabetic NephropathyEman Al Shawaf0Mohamed Abu-Farha1Sriraman Devarajan2Zahra Alsairafi3Irina Al-Khairi4Preethi Cherian5Hamad Ali6Aditi Mathur7Fahd Al-Mulla8Abdulnabi Al Attar9Jehad Abubaker10Biochemistry and Molecular Biology, Dasman Diabetes Institute, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, KuwaitNational Dasman Diabetes Biobank, Dasman Diabetes Institute, KuwaitDepartment of Pharmacy Practice, Faculty of Pharmacy, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, KuwaitFunctional Genomic Unit, Dasman Diabetes Institute, KuwaitNational Dasman Diabetes Biobank, Dasman Diabetes Institute, KuwaitFunctional Genomic Unit, Dasman Diabetes Institute, KuwaitDiabetology Unit, Amiri Hospital, Dasman Diabetes Institute, KuwaitNational Dasman Diabetes Biobank, Dasman Diabetes Institute, KuwaitBackground. ANGPTL4 is a glycoprotein that is involved in regulating triglyceride metabolism by inhibiting LPL activity under fasting conditions. Additionally, ANGPTL4 has been suggested as a link between hypertriglyceridemia and albuminuria in the nephrotic syndrome. In this study, we examined levels of circulating ANGPTL4 in people with diabetic nephropathy (DN) and its association with established DN-associated proteins such as IGFBP1 and IGFBP4. Methods. We quantified circulating ANGPTL4, IGFBP1, IGFBP3, and IGFBP4 in fasting plasma samples of 122 Kuwaiti participants using a multiplexing assay. The study involved 36 controls, as well as 86 people with type 2 diabetes (T2D) including 37 people with normal kidney function and 49 people with DN. Results. ANGPTL4 level was increased in people with DN (241.56±14.1 μg/ml) compared to the control group (178.43±24.09 μg/ml). The increase in ANGPTL4 correlated with clinical parameters of DN including albumin-to-creatinine ratio (r=0.271, P=0.002), serum creatinine (r=0.381, P=0.0001), and eGFR (r=−0.349, P<0.0001). Furthermore, ANGPTL4 correlated positively with both IGFBP1 (r=0.202, P=0.026) and IGFBP4 (r=0.364, P<0.0001). Multiple regression analysis showed increased IGFBP1 and TG as predictors of higher ANGPTL4 in people with DN. In people with T2D, only IGFBP1 acted as a positive predictor of a rise in ANGPTL4. Conclusion. In this study, our data showed a significant increase in circulating ANGPTL4, IGFBP1, and IGFBP4 in patients with DN. The elevation in ANGPTL4 correlated significantly with clinical markers of DN such as ACR, serum creatinine, and eGFR, as well as IGFBP1 and IGFBP4. Altogether, this suggests a potential role for ANGPTL4 in DN perhaps through its role in inhibiting LPL activity and promotes ANGPTL4 as a biochemical marker for the detection of a diabetic kidney disease in patients with T2D.http://dx.doi.org/10.1155/2019/4943191
spellingShingle Eman Al Shawaf
Mohamed Abu-Farha
Sriraman Devarajan
Zahra Alsairafi
Irina Al-Khairi
Preethi Cherian
Hamad Ali
Aditi Mathur
Fahd Al-Mulla
Abdulnabi Al Attar
Jehad Abubaker
ANGPTL4: A Predictive Marker for Diabetic Nephropathy
Journal of Diabetes Research
title ANGPTL4: A Predictive Marker for Diabetic Nephropathy
title_full ANGPTL4: A Predictive Marker for Diabetic Nephropathy
title_fullStr ANGPTL4: A Predictive Marker for Diabetic Nephropathy
title_full_unstemmed ANGPTL4: A Predictive Marker for Diabetic Nephropathy
title_short ANGPTL4: A Predictive Marker for Diabetic Nephropathy
title_sort angptl4 a predictive marker for diabetic nephropathy
url http://dx.doi.org/10.1155/2019/4943191
work_keys_str_mv AT emanalshawaf angptl4apredictivemarkerfordiabeticnephropathy
AT mohamedabufarha angptl4apredictivemarkerfordiabeticnephropathy
AT sriramandevarajan angptl4apredictivemarkerfordiabeticnephropathy
AT zahraalsairafi angptl4apredictivemarkerfordiabeticnephropathy
AT irinaalkhairi angptl4apredictivemarkerfordiabeticnephropathy
AT preethicherian angptl4apredictivemarkerfordiabeticnephropathy
AT hamadali angptl4apredictivemarkerfordiabeticnephropathy
AT aditimathur angptl4apredictivemarkerfordiabeticnephropathy
AT fahdalmulla angptl4apredictivemarkerfordiabeticnephropathy
AT abdulnabialattar angptl4apredictivemarkerfordiabeticnephropathy
AT jehadabubaker angptl4apredictivemarkerfordiabeticnephropathy