The pro-inflammatory marker soluble suppression of tumorigenicity-2 (ST2) is reduced especially in diabetic morbidly obese patients undergoing bariatric surgery

Demyanets, Svitlana; Kaun, Christoph; Kaider, Alexandra; Speidl, Walter S.; Prager, Manfred; Oravec, Stanislav; Hohensinner, Philipp J.; Wojta, Johann; Rega‐Kaun, Gersina

doi:10.1186/s12933-020-01001-y

Cited by 16 publications

(14 citation statements)

References 49 publications

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“…In contrast to the modest weight loss achieved in our study in either arm, a drastic body weight reduction associated with bariatric surgery led to a significant reduction in sST2 especially in diabetic patients [ 31 ]. This is probably related to the profound cardiometabolic reprogramming induced by bariatric surgery [ 32 ].…”

Section: Discussionmentioning

confidence: 56%

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Simeone

Tripaldi

Michelsen

et al. 2022

Cardiovasc Diabetol

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Background Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. Methods Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. Results Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment. Conclusions Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36

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Section: Discussionmentioning

confidence: 56%

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Simeone

Tripaldi

Michelsen

et al. 2022

Cardiovasc Diabetol

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“…Bariatric surgery in severely obese diabetes patients improves metabolic status, and circulating sST2 levels decrease with improvements in liver function and lipid metabolism markers 32 . In line with these findings, we found that sST2 is correlated with DM and dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

“…In type 2 diabetes patients with normal blood glucose tolerance, circulating sST2 levels were significantly higher and were significantly associated with fasting blood glucose and HbA1c ( 31 ). Bariatric surgery in severely obese diabetes patients improves metabolic status, and circulating sST2 levels decrease with improvements in liver function and lipid metabolism markers ( 32 ). In line with these findings, we found that sST2 is correlated with DM and dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Soluble ST2 levels for predicting the presence and severity of metabolic syndrome

Zong

Fan

Zhang

et al. 2021

Endocrine Connections

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To explore the relationship between soluble ST2 (sST2) and metabolic syndrome (MetS) and determine whether sST2 levels can predict the presence and severity of MetS. We evaluated 550 consecutive subjects (58.91 ± 9.69 years, 50% male) with or without MetS from the Department of Vascular and Cardiology, Shanghai Jiao Tong University-Affiliated Ruijin Hospital. Serum sST2 concentrations were measured. The participants were divided into three groups according to the sST2 tertiles. Univariate and multivariable logistic regression models were used to evaluate the association between serum sST2 concentrations and the presence of MetS. Serum sST2 concentrations were significantly higher in the MetS group than in those in the no MetS group (14.80 ± 7.01 vs. 11.58 ± 6.41 ng/ml, P < 0.01). Subjects with more MetS components showed higher levels of sST2. sST2 was associated with the occurrence of MetS after multivariable adjustment as a continuous log-transformed variable (per 1 SD, odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.13-1.80, P < 0.01). Subgroup analysis showed that individuals with MetS have significantly higher levels of sST2 than those without MetS regardless of sex and age.High serum sST2 levels were significantly and independently associated with the presence and severity of MetS. Thus, sST2 levels may be a novel biomarker and clinical predictor of MetS.

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“…IL-33 serves as an important local link between tissue injury or metabolic disturbances and a physiological response to limiting and repairing tissue damage [ 45 ]. It has been shown that circulating sST2 is associated with markers of liver function and lipid metabolism in severely obese patients and that a reduction in sST2 occurs after successful bariatric surgery, most prominently in patients with diabetes [ 46 ]. IL-33 and sST2 are abundantly expressed in adipose tissues, and IL-33 levels are correlated with high BMI, suggesting an association of IL-33 with obesity and diabetes [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

Duan

Cai

et al. 2021

Cardiovasc Diabetol

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Background Soluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of sST2 in patients with established CAD and its predictive value in CAD patients with and without type 2 diabetes mellitus (T2DM). Methods A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between sST2 and outcomes was investigated using multivariable Cox regression. Results During a median follow-up of 6.4 years, MACEs occurred in 775 patients, and 275 patients died. Multiple Cox regression models showed that a higher level of sST2 was an independent predictor of MACEs development (HR = 1.36, 95% CI 1.17–1.56, p < 0.001) and all-cause death (HR = 2.01, 95% CI 1.56–2.59, p < 0.001). The addition of sST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-index, net reclassification index, and integrated discrimination improvement, all p < 0.05). In subgroup analysis depending on diabetes status, the diabetes group had a significantly higher level of sST2, which remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models. The area under the curve (AUC) of CAD patients with diabetes mellitus was significantly higher than that of those without T2DM. For MACEs, the AUC was 0.737 (patients with T2DM) vs 0.620 (patients without T2DM). For all-cause death, the AUC was 0.923 (patients with T2DM) vs 0.789 (patients without T2DM). Conclusions A higher level of sST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. sST2 has strong predictive value for cardiovascular adverse events in CAD patients with T2DM, and these results provide new evidence for the role of sST2.

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The pro-inflammatory marker soluble suppression of tumorigenicity-2 (ST2) is reduced especially in diabetic morbidly obese patients undergoing bariatric surgery

Cited by 16 publications

References 49 publications

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Soluble ST2 levels for predicting the presence and severity of metabolic syndrome

Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

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