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Article Abstract
Context: Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. It exists in a membrane-bound form and a soluble form (sDPP-4). Initial human studies suggested sDPP-4 to be an adipokine involved in metabolic inflammation. However, recent mechanistic data in genetically modified mice has questioned these findings.
Objectives: We examined circulating sDPP-4 in a cohort of n = 451 humans with different metabolic phenotypes and during 3 different weight loss interventions (n = 101) to further clarify its role in human physiology and metabolic diseases.
Design: sDPP-4 serum concentrations were measured by enzyme-linked immunosorbent assay and related to several phenotyping data including gut microbiome analysis.
Results: sDPP-4 increased with age and body weight and was positively associated with insulin resistance and hypertriglyceridemia but was reduced in manifest type 2 diabetes. In addition, we found reduced serum concentrations of sDPP-4 in subjects with arterial hypertension. In contrast to earlier reports, we did not identify an association with systemic markers of inflammation. Impaired kidney and liver functions significantly altered sDPP-4 concentrations while no relation to biomarkers for heart failure was observed. Having found increased levels of sDPP-4 in obesity, we studied surgical (gastric bypass and sleeve gastrectomy) and nonsurgical interventions, revealing a significant association of sDPP-4 with improvement of liver function tests but not with changes in body weight.
Conclusions: Our data suggest that sDPP-4 is related to hepatic abnormalities in obesity rather than primarily functioning as an adipokine and that sDPP-4 is implicated both in glucose and in lipid metabolism, but not fundamentally in systemic inflammation.
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| http://dx.doi.org/10.1210/clinem/dgaa758 | DOI Listing |
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Article Synopsis
- The study aimed to explore the connection between serum soluble dipeptidyl peptidase-4 (sDDP-4) levels and liver fibrosis in type 2 diabetes patients by using liver stiffness measurements (LSM) and FAST scores through transient elastography.
- In the cross-sectional analysis of 115 type 2 diabetes patients, significant results showed that higher serum sDPP-4 levels were linked with elevated liver enzymes, CAP, LSM, and FAST scores, indicating more severe liver fibrosis.
- Ultimately, the findings suggest that increased serum sDDP-4 is closely associated with liver fibrosis severity and is significantly higher in patients with LSM indicative of probable cirrhosis, highlighting a potential biomarker for liver