Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy

Q: What are the key findings of this study?

Circulating ANGPTL8 levels were higher in patients with diabetic nephropathy compared to those with type 2 diabetes alone.

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Type 2 diabetes with and without diabetic nephropathy (n=86). Intervention: Diabetic nephropathy vs. Type 2 diabetes without nephropathy. Primary outcome: Circulating ANGPTL8 levels (p=<0.001).

Q: What does this research mean for the field?

Diabetic nephropathy is associated with significantly higher circulating ANGPTL8 levels compared to type 2 diabetes alone, which correlates exclusively with IGFBP-4, suggesting their potential as combined diagnostic biomarkers. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate circulating ANGPTL8 concentrations in patients with diabetic nephropathy and investigate its relationship with insulin-like growth factor-binding proteins.

Hana T Al-Majed; Mohamed Abu‐Farha; Eman Alshawaf; Sriraman Devarajan; Zahra Alsairafi; Ashraf E. EL-Helaly; Preethi Cherian; Irina Al‐Khairi; Hamad Ali; Rose Mol Jose; Thangavel Alphonse Thanaraj; Ebaa Al‐Ozairi; Fahd Al‐Mulla; Abdulnabi Al Attar; Jehad Abubaker

doi:10.3390/ijms241814244

September 18, 2023International Journal of Molecular SciencesOpen Access

Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy

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Key result

Diabetic nephropathy is linked to ~2-fold higher circulating ANGPTL8 levels in patients with T2D.

P<0.001
n=86

Figures

Why the study?

The potential link between ANGPTL8 and IGFBPs in diabetic nephropathy had not been explored.

Are circulating ANGPTL8 and IGFBP4 levels elevated in patients with diabetic nephropathy compared to those with type 2 diabetes alone?

Key Points

To evaluate circulating ANGPTL8 concentrations in patients with diabetic nephropathy and investigate its relationship with insulin-like growth factor-binding proteins.
Enrolled 86 Kuwaiti participants grouped into type 2 diabetes mellitus without nephropathy (N=37) and diabetic nephropathy (N=49), matched for age and body mass index.
Measured circulating levels of ANGPTL8, IGFBP-1, IGFBP-3, and IGFBP-4, analyzing associations with renal markers including eGFR and serum creatinine.
Evaluated diagnostic accuracy using receiver operating characteristic curve analysis and identified independent predictors through multiple stepwise regression.
Circulating ANGPTL8 was significantly elevated in diabetic nephropathy (4443.35 ± 396 ng/mL) compared to type 2 diabetes (2059.73 ± 216 ng/mL, p < 0.001), alongside higher IGFBP-4 levels (627.8 ± 92.80 ng/mL vs. 278.9 ± 48.71 ng/mL, p = 0.003).
ANGPTL8 correlated positively with IGFBP-4 (r = 0.468, p < 0.001) and serum creatinine (r = 0.37, p = 0.007), while correlating negatively with eGFR (r = −0.44, p = 0.002) in diabetic nephropathy.
Combined ANGPTL8 and IGFBP-4 yielded an area under the ROC curve of 0.76 (95% CI: 0.69–0.84, p < 0.001) with 85.9% specificity for identifying diabetic nephropathy.

Study Design

Type

Cross-Sectional (n=86)

Multicenter

No

Structured PICO

Are circulating ANGPTL8 and IGFBP4 levels elevated in patients with diabetic nephropathy compared to those with type 2 diabetes alone?

P

Population

86 Kuwaiti adults with type 2 diabetes, including 49 with diabetic nephropathy and 37 without, assessed in a cross-sectional study.

E

Exposure

Diabetic nephropathy (exposure)

C

Comparator

Type 2 diabetes without nephropathy

O

Outcome

Circulating ANGPTL8 levelssurrogate

Main Result

Absolute Event Rate: 4443.35% vs 2059.73%

p-value: p=<0.001

ANGPTL8 and IGFBP-4 are significantly elevated in diabetic nephropathy and may serve as potential diagnostic biomarkers.

Limitations

Cross-sectional design makes it difficult to establish the biological role and cause-effect relationship
Cross-sectional design
Difficult to establish the biological role of these proteins and their potential contribution to the pathophysiology of DN

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Implication

Supports ANGPTL8 as potential biomarker in diabetic nephropathy; hypothesis-generating and requires prospective validation before clinical use.

Abstract

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 (p < 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 (p < 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), p < 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.

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Cite This Study

Al-Majed et al. (2023) conducted a cross-sectional in Type 2 diabetes with and without diabetic nephropathy (n=86). Diabetic nephropathy vs. Type 2 diabetes without nephropathy was evaluated on Circulating ANGPTL8 levels (p=<0.001). Circulating ANGPTL8 levels were higher in patients with diabetic nephropathy compared to those with type 2 diabetes alone.

synapsesocial.com/papers/6a1ecada6e6b94f521a457f4 https://doi.org/10.3390/ijms241814244

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Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Increased Levels of Circulating IGFBP4 and ANGPTL8 with a Prospective Role in Diabetic Nephropathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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