Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy
Diabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14244 |
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| author | Hana Th. AlMajed Mohamed Abu-Farha Eman Alshawaf Sriraman Devarajan Zahra Alsairafi Ashraf Elhelaly Preethi Cherian Irina Al-Khairi Hamad Ali Rose Mol Jose Thangavel Alphonse Thanaraj Ebaa Al-Ozairi Fahd Al-Mulla Abdulnabi Al Attar Jehad Abubaker |
| author_facet | Hana Th. AlMajed Mohamed Abu-Farha Eman Alshawaf Sriraman Devarajan Zahra Alsairafi Ashraf Elhelaly Preethi Cherian Irina Al-Khairi Hamad Ali Rose Mol Jose Thangavel Alphonse Thanaraj Ebaa Al-Ozairi Fahd Al-Mulla Abdulnabi Al Attar Jehad Abubaker |
| author_sort | Hana Th. AlMajed |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis constituents. The potential link between ANGPTL8 and IGFBPs in DN has not been explored before. Here, we assessed changes in the circulating ANGPTL8 levels in patients with DN and its association with IGFBP-1, -3, and -4. Our data revealed a significant rise in circulating ANGPTL8 in people with DN, 4443.35 ± 396 ng/mL compared to 2059.73 ± 216 ng/mL in people with T2D (<i>p</i> < 0.001). Similarly, levels of IGFBP-3 and -4 were significantly higher in people with DN compared to the T2D group. Interestingly, the rise in ANGPTL8 levels correlated positively with IGFBP-4 levels in T2DM patients with DN (<i>p</i> < 0.001) and this significant correlation disappeared in T2DM patients without DN. It also correlated positively with serum creatinine and negatively with the estimated glomerular filtration rate (eGFR, All < 0.05). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and IGFBP4 was 0.76 (0.69–0.84), <i>p</i> < 0.001, and the specificity was 85.9%. In conclusion, our results showed a significant increase in ANGPTL8 in patients with DN that correlated exclusively with IGFBP-4, implicating a potential role of both proteins in the pathophysiology of DN. Our findings highlight the significance of these biomarkers, suggesting them as promising diagnostic molecules for the detection of diabetic nephropathy. |
| first_indexed | 2024-03-10T22:39:18Z |
| format | Article |
| id | doaj.art-92406767de3040088aca7c88ebe8d7f1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:18Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-92406767de3040088aca7c88ebe8d7f12023-11-19T11:09:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181424410.3390/ijms241814244Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic NephropathyHana Th. AlMajed0Mohamed Abu-Farha1Eman Alshawaf2Sriraman Devarajan3Zahra Alsairafi4Ashraf Elhelaly5Preethi Cherian6Irina Al-Khairi7Hamad Ali8Rose Mol Jose9Thangavel Alphonse Thanaraj10Ebaa Al-Ozairi11Fahd Al-Mulla12Abdulnabi Al Attar13Jehad Abubaker14Applied Health Science Department, College of Health Sciences, Kuwait 15462, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait 15462, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait 15462, KuwaitNational Dasman Diabetes Biobank, Dasman Diabetes Institute, Kuwait 15462, KuwaitDepartment of Pharmacy Practice, Faculty of Pharmacy, Kuwait 15462, KuwaitClinical Laboratory, Amiri Hospital Kuwait, Kuwait 15462, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait 15462, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Kuwait 15462, KuwaitNational Dasman Diabetes Biobank, Dasman Diabetes Institute, Kuwait 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Kuwait 15462, KuwaitMedical Division, Dasman Diabetes Institute, Kuwait 15462, KuwaitGenetics and Bioinformatics, Dasman Diabetes Institute, Kuwait 15462, KuwaitDiabetology Unit, Amiri Hospital, Dasman Diabetes Institute, Kuwait 15462, KuwaitBiochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait 15462, KuwaitDiabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis constituents. The potential link between ANGPTL8 and IGFBPs in DN has not been explored before. Here, we assessed changes in the circulating ANGPTL8 levels in patients with DN and its association with IGFBP-1, -3, and -4. Our data revealed a significant rise in circulating ANGPTL8 in people with DN, 4443.35 ± 396 ng/mL compared to 2059.73 ± 216 ng/mL in people with T2D (<i>p</i> < 0.001). Similarly, levels of IGFBP-3 and -4 were significantly higher in people with DN compared to the T2D group. Interestingly, the rise in ANGPTL8 levels correlated positively with IGFBP-4 levels in T2DM patients with DN (<i>p</i> < 0.001) and this significant correlation disappeared in T2DM patients without DN. It also correlated positively with serum creatinine and negatively with the estimated glomerular filtration rate (eGFR, All < 0.05). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and IGFBP4 was 0.76 (0.69–0.84), <i>p</i> < 0.001, and the specificity was 85.9%. In conclusion, our results showed a significant increase in ANGPTL8 in patients with DN that correlated exclusively with IGFBP-4, implicating a potential role of both proteins in the pathophysiology of DN. Our findings highlight the significance of these biomarkers, suggesting them as promising diagnostic molecules for the detection of diabetic nephropathy.https://www.mdpi.com/1422-0067/24/18/14244diabetic nephropathyANGPTL8IGFBP4IGF-binding proteinstype 2 diabetes |
| spellingShingle | Hana Th. AlMajed Mohamed Abu-Farha Eman Alshawaf Sriraman Devarajan Zahra Alsairafi Ashraf Elhelaly Preethi Cherian Irina Al-Khairi Hamad Ali Rose Mol Jose Thangavel Alphonse Thanaraj Ebaa Al-Ozairi Fahd Al-Mulla Abdulnabi Al Attar Jehad Abubaker Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy International Journal of Molecular Sciences diabetic nephropathy ANGPTL8 IGFBP4 IGF-binding proteins type 2 diabetes |
| title | Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy |
| title_full | Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy |
| title_fullStr | Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy |
| title_full_unstemmed | Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy |
| title_short | Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy |
| title_sort | increased levels of circulating igfbp4 and angptl8 with a prospective role in diabetic nephropathy |
| topic | diabetic nephropathy ANGPTL8 IGFBP4 IGF-binding proteins type 2 diabetes |
| url | https://www.mdpi.com/1422-0067/24/18/14244 |
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