To the editor
We have read with great interest the study by Trojak et al1 concerning the association between serum pentraxin 3 (PTX3) levels and several established cardiovascular risk factors in patients with type 2 diabetes (T2D) with or without nonalcoholic fatty liver disease (NAFLD). Of note, in the whole cohort, the relative frequency of major comorbidities such as hypertension, dyslipidemia, and coronary artery disease was high, reaching up to 86.2%, 68.7%, and 36.2%, respectively, while patients’ average glycemic control was rather insufficient.1
Researchers have shown that in the NAFLD subgroup, serum PTX3 levels correlated positively and significantly with total and low-density lipoprotein cholesterol, triglycerides, apolipoprotein C3, and apolipoprotein B100.1 The latter might provide novel pathophysiologic insights into the T2D/NAFLD concomitance and the related cardiovascular disease, leading to personalized treatment pathways.
Based on the aforementioned observations made by Trojak et al,1 we question the potential impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on PTX3. These agents have now evolved as key players in the therapeutic management of T2D, especially in patients with established atherosclerotic cardiovascular disease, constituting the second-line treatment option, along with sodium-glucose cotransporter 2 inhibitors. In addition, they represent a promising treatment option in NAFLD/nonalcoholic steatohepatitis. In the hallmark LEAN (Liraglutide Efficacy and Action in Nonalcoholic Steatohepatitis) trial, liraglutide, one of the most widely used GLP-1RAs, led to a significant resolution of nonalcoholic steatohepatitis and delay in fibrosis progression, as compared with placebo; however, relevant evidence is still considered insufficient for treatment guidelines.2
Only 3 studies have assessed the direct impact of GLP-1RAs on PTX3. In their experimental study, Shiraki et al3 demonstrated that treatment with liraglutide led to a significant downregulation of the expression of PTX3 in primary human umbilical vein endothelial cells incubated with tumor necrosis factor α, (P <0.05), reinforcing the potential anti-inflammatory role of liraglutide. In a streptozotocin-induced diabetic rat model, Artunc-Ulkumen et al4 showed that treatment with exenatide resulted in a significant decrease in serum PTX3 levels, as compared with the nontreated group (P <0.05), ameliorating the glucotoxicity-related inflammatory process. In the only human study available in the literature, Suzuki et al5 found that 6-month treatment with liraglutide in 46 patients with T2D led to an increase in serum PTX3 levels (P <0.0001), which was interpreted on the basis of higher mRNA expression of PTX3 in adipocytes isolated from the visceral adipose tissue than in adipocytes isolated from the subcutaneous adipose tissue along with increase in the visceral to subcutaneous fat ratio.
Collectively, these data might suggest that PTX3 appears as a novel treatment target for GLP-1RAs, a drug class promising to bridge the gap between T2D and NAFLD and to prevent (on either primary or secondary basis) the related cardiovascular disease. Prospective human studies utilizing GLP-1RAs in patients with T2D and NAFLD, evaluating its effect on PTX3, are required in order to elucidate this reasonable and interesting hypothesis.
Dimitrios Patoulias, MD, 2nd Propedeutic Department of Internal Medicine, Hippokration General Hospital, Konstantinoupoleos 49, 54642, Thessaloniki, Greece, phone: +306946900777, email: dipatoulias@gmail.com
Dimitrios Patoulias, Maria-Styliani Kalogirou, Konstantinos Stavropoulos, Konstantinos Imprialos, Michael Doumas (DP, MSK, KS, KI, MD: 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece; KS, KI: Veterans Affairs Medical Center, Georgetown University, Washington, District of Columbia, United States; MD: Veterans Affairs Medical Center, George Washington University, Washington, District of Columbia, United States)
None declared.
Patoulias D, Kalogirou MS, Stavropoulos K, et al. Pentraxin 3 in patients with type 2 diabetes and nonalcoholic fatty liver disease: a promising treatment target for glucagon-like peptide-1 receptor agonists. Pol Arch Intern Med. 2019; 129: 648-649. doi:10.20452/pamw.14998
- 1.
- Trojak A, Waluś-Miarka M, Kapusta M, et al. Serum pentraxin 3 concentration in patients with type 2 diabetes and non-alcoholic fatty liver disease. Pol Arch Intern Med. 2019; 129: 499-505.
- 2.
- Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016; 387: 679-690.
- 3.
- Shiraki A, Oyama J, Komoda H, et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-α-induced oxidative stress and inflammation in endothelial cells. Atherosclerosis. 2012; 221: 375-382.
- 4.
- Artunc-Ulkumen B, Pala HG, Pala EE, et al. Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats. Gynecol Endocrinol. 2015; 31: 196-201.
- 5.
- Suzuki D, Toyoda M, Kimura M, et al. Effects of liraglutide, a human glucagon-like peptide-1 analogue, on body weight, body fat area and body fat-related markers in patients with type 2 diabetes mellitus. Intern Med. 2013; 52: 1029-1034.Crossref