# Decreased Serum Adipose Triglyceride Lipase Level Is Associated With Renal Function Impairment in Patients With Type 2 Diabetes

**Authors:** Ying Wang, Tongtong Liu, Nan Li, Tingting Zhao, Xiai Wu, Yanmei Wang, Xi Dong, Hailing Zhao, Weijing Liu, Ping Li

PMC · DOI: 10.1155/jdr/9987648 · Journal of Diabetes Research · 2025-07-24

## TL;DR

Lower levels of a fat-breaking enzyme in the blood are linked to worse kidney function in people with type 2 diabetes, suggesting it could help detect kidney disease early.

## Contribution

This study identifies serum ATGL as a potential early biomarker for diabetic kidney disease.

## Key findings

- Serum ATGL levels were significantly lower in T2DM and DKD patients compared to healthy controls.
- Lower ATGL levels correlated with higher urine protein and lower kidney function metrics.
- Combining ATGL with traditional markers improved diagnostic sensitivity for DKD.

## Abstract

Background: Diagnosing diabetic kidney disease (DKD) remains a significant challenge. Research has increasingly focused on kidney injury resulting from lipid metabolism disorders. Adipose triglyceride lipase (ATGL), a pivotal enzyme in lipolysis, is essential for maintaining lipid metabolism balance. The objective of this study was to assess whether serum ATGL could serve as an early biomarker for DKD.

Methods: The study divided 236 participants into four groups: healthy controls (n = 59), Type 2 diabetes mellitus (T2DM) with albumin-to-creatinine ratio (ACR) < 30 mg/g (n = 80), microalbuminuria (L-DKD) with ACR 30–300 mg/g (n = 41), and macroalbuminuria (H-DKD) with ACR ≥ 300 mg/g (n = 56). Relevant clinical data were collected, and serum levels of ATGL, kidney injury molecule-1 (KIM-1), and tumor necrosis factor-1 (TNFR-1) were measured. Various statistical analyses, including Spearman's correlation test, receiver operating characteristic curve analysis, multivariate logistic regression, and restricted cubic spline (RCS), were employed to assess the relationship between serum ATGL levels and renal function impairment in DKD.

Results: Serum ATGL levels were notably lower in the T2DM, L-DKD, and H-DKD groups compared to healthy controls. Positive correlations were found between serum ATGL levels and estimated glomerular filtration rates (eGFR), while negative correlations were observed with diabetes duration, hypertension history, hyperlipidemia, urine ACR (UACR), 24-h urine total protein (UTP), serum creatinine (SCr), blood urea nitrogen, uric acid, TNFR-1, and KIM-1/creatinine (KIM-1/Cr) levels (p < 0.05). The receiver operating characteristic curve analysis demonstrated that the diagnostic performance of ATGL, when combined with traditional clinical markers, can enhance sensitivity. When participants were grouped by serum ATGL quartiles, it was observed that higher ATGL levels corresponded with lower UACR, 24 h-UTP, SCr, and TNFR-1 levels and higher eGFR. The odds ratios for elevated UACR and 24 h-UTP decreased, and eGFR increased with higher ATGL quartiles. Both univariate and multivariate logistic regression analyses indicated that serum ATGL is a protective factor against DKD development, even after adjusting for potential confounders. RCS analysis indicated a nonlinear dose–response association between serum ATGL levels and renal function metrics, specifically UACR and eGFR, in patients with DKD.

Conclusion: Serum ATGL levels are linked to reduced renal function in T2DM patients. A decline in ATGL levels corresponded with a nonlinear rise in UACR and a drop in eGFR, suggesting that serum ATGL may serve as a potential biomarker for DKD development.

## Linked entities

- **Proteins:** PNPLA2 (patatin like domain 2, triacylglycerol lipase), HAVCR1 (hepatitis A virus cellular receptor 1), TNFRSF1A (TNF receptor superfamily member 1A)
- **Diseases:** type 2 diabetes (MONDO:0005148), diabetic kidney disease (MONDO:0005016), DKD (MONDO:0005016)

## Full-text entities

- **Genes:** PPARD (peroxisome proliferator activated receptor delta) [NCBI Gene 5467] {aka FAAR, NR1C2, NUC1, NUCI, NUCII, PPARB}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289] {aka B120, BAF250, BAF250a, BM029, C1orf4, CSS2}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, PNPLA2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 57104] {aka 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}
- **Diseases:** metabolic syndromes (MESH:D024821), fatty liver (MESH:D005234), Lipid metabolism disorders (MESH:D052439), Renal injury (MESH:D007674), DM (MESH:D003920), insulin resistance (MESH:D007333), ischemia (MESH:D007511), inflammatory (MESH:D007249), ESRD (MESH:D007676), albuminuria (MESH:D000419), T2DM (MESH:D003924), fibrosis (MESH:D005355), CKD (MESH:D051436), unilateral (MESH:D046088), death (MESH:D003643), LD accumulation (MESH:C579880), Renal lipotoxicity (MESH:D006030), obese (MESH:D009765), reperfusion injury (MESH:D015427), hypertension (MESH:D006973), cerebrovascular disease (MESH:D002561), cardiovascular conditions (MESH:D002318), hyperlipidemia (MESH:D006949), ureteral obstruction (MESH:D014517), hypoxic (MESH:D002534), overweight (MESH:D050177), dyslipidemia (MESH:D050171), DKD (MESH:D003928), proteinuria (MESH:D011507), reduced renal function (MESH:D001523), H (MESH:D000848), ectopic lipid deposition (MESH:D011017)
- **Chemicals:** fatty acid (MESH:D005227), diacylglycerol (MESH:D004075), glucose (MESH:D005947), cholesterol (MESH:D002784), HCY (MESH:D006710), PM2.5 (-), Fenofibrate (MESH:D011345), Cr (MESH:D003404), fat (MESH:D005223), reactive oxygen species (MESH:D017382), TG (MESH:D014280), UA (MESH:D014527), Lipid (MESH:D008055), Cr (MESH:D002857), urea nitrogen (MESH:C530477), blood glucose (MESH:D001786), palmitic acid (MESH:D019308), FFA (MESH:D005230)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12313390/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12313390/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12313390/full.md

---
Source: https://tomesphere.com/paper/PMC12313390