The effect of bariatric surgery on lipid profile and the qualitative characteristics of lipoproteins was analyzed in morbidly obese subjects. Thirteen obese patients underwent bariatric surgery. Plasma samples were obtained before surgery and at 6 and 12 months after the intervention. Thirteen healthy subjects comprised the control group. Lipid profile, hsCRP, and the composition and functional characteristics of VLDL, LDL, and HDL were assessed. At baseline, plasma from subjects with obesity had more triglycerides, VLDLc, and hsCRP, and less HDLc than the control group. These levels progressively normalized after surgery, although triglyceride and hsCRP levels remained higher than those in the controls. The main differences in lipoprotein composition between the obese subjects and the controls were increased apoE in VLDL, and decreased cholesterol and apoJ and increased apoC-III content in HDL. The pro-/anti-atherogenic properties of LDL and HDL were altered in the subjects with obesity at baseline compared with the controls, presenting smaller LDL particles that are more susceptible to modification and smaller HDL particles with decreased antioxidant capacity. Bariatric surgery normalized the composition of lipoproteins and improved the qualitative characteristics of LDL and HDL. In summary, patients with obesity present multiple alterations in the qualitative properties of lipoproteins compared with healthy subjects. Bariatric surgery reverted most of these alterations.

Heart failure (HF) is a major complication of type 2 diabetes (T2D), with HF with preserved ejection fraction (HFpEF) now representing the most frequent phenotype. However, its clinical profile, prognosis, and treatment patterns compared with HF with reduced ejection fraction (HFrEF) remain insufficiently characterized. To compare characteristics, outcomes, and longitudinal management of HFpEF versus HFrEF in T2D patients. Methods: This prespecified subanalysis of the nationwide, prospective DIABET-IC cohort included 1517 patients with T2D recruited across 58 Spanish centers and followed for three years. HF phenotypes were defined according to the 2016 ESC guidelines criteria. Baseline characteristics, outcomes (mortality, hospitalizations, and progression), and therapeutic patterns were assessed. At baseline, 490 patients had HF (50.2% HFrEF, 30.6% HFpEF, 19.2% HFmrEF). HFpEF patients were older, more often female, and had higher prevalence of obesity, hypertension, and metabolic syndrome, whereas HFrEF was more strongly associated with ischemic heart disease, prior ST-elevation myocardial infarction (STEMI), and conduction disturbances. During follow-up, HFpEF was the predominant incident phenotype (46.6% of new cases), and 4.7% progressed to HFrEF. Mortality was similarly elevated in both phenotypes; HF hospitalizations tended to be higher in HFrEF, while acute coronary syndromes were more frequent in HFpEF. HFrEF patients more often received guideline-directed therapies, whereas the pre-guideline era for HFpEF, with greater uptake of SGLT2 inhibitors over time, limited used of GLP-1 receptor agonists. Notably, > 20% of HFpEF patients had natriuretic peptide levels below diagnostic thresholds, highlighting underdiagnosis. HFpEF is the most frequent HF phenotype in the T2D population, with outcomes comparable to HFrEF yet frequently underdiagnosed and undertreated. Improved screening strategies and broader adoption of evidence-based therapies—particularly SGLT2 inhibitors—are urgently needed for this high-risk population.

Background: Increased epicardial adipose tissue (EAT) volume is a common feature in type 2 diabetes (T2DM) which is directly associated with heart failure and advanced atherosclerosis. We aimed to evaluate lipoprotein-related biomarkers of EAT volume in T2DM patients before and after glycemic control. Methods: This study included 36 T2DM patients before and after optimization of glycemic control and on 14 healthy controls (HCs). EAT volume was measured using computed tomography imaging indexed to the body surface area (iEAT). Biochemical and lipid profiles were determined using commercial methods. Lipoproteins were isolated by ultracentrifugation, and variables of lipoprotein function were assessed. Multivariable regression analysis was used to find variables independently associated with iEAT. Results: iEAT was higher in T2DM than in controls and decreased with glycemic optimization. HDLs from T2DM had less apoA-I and cholesterol and more apoC-III and triglycerides. LDLs from T2DM had more triglycerides and apoB and smaller sizes than those from HCs. Significant correlations were found between iEAT and age, BMI, HbA1c, GGT, VLDLc, triglycerides, LDL size, apoA-I in HDL, and apoC-III in HDL. In the multivariable regression analysis, age, LDL size, and GGT associations remained statistically significant, and predicted 50% of the variability in EAT volume. ROC analysis using these variables showed an AUC of 0.835. Conclusions: Qualitative characteristics of lipoproteins were altered in T2DM. Multivariable analysis showed that LDL size and GGT plasma levels were independently associated with iEAT volume, suggesting that these variables might be useful biomarkers for stratifying T2DM patients with increased EAT volume.

Lipoprotein characteristics were analyzed in familial combined hyperlipidemia (FCH) patients before and after statin treatment. Twenty-six FCH patients were classified according to the presence (HTG group, n = 13) or absence (normotriglyceridemic (NTG) group, n = 13) of hypertriglyceridemia. Fifteen healthy subjects comprised the control group. Lipid profile, inflammation markers, and qualitative characteristics of lipoproteins were assessed. Both groups of FCH subjects showed high levels of plasma C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and apolipoprotein J. Statins reverted the increased levels of Lp-PLA2 and CRP. Lipoprotein composition alterations detected in FCH subjects were much more frequent in the HTG group, leading to dysfunctional low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In the HTG group, LDL was smaller, more susceptible to oxidation, and contained more electronegative LDL (LDL(-)) compared to the NTG and control groups. Regarding HDL, the HTG group had less Lp-PLA2 activity than the NTG and control groups. HDL from both FCH groups was less anti-inflammatory than HDL from the control group. Statins increased LDL size, decreased LDL(-), and lowered Lp-PLA2 in HDL from HTG. In summary, pro-atherogenic alterations were more frequent and severe in the HTG group. Statins improved some alterations, but many remained unchanged in HTG.

Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 ± 21.67 vs. 36.84 ± 16.57 cm³/m², p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 (β = 0.27, p = 0.027) and sST2 (β = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients.

Heart failure (HF) is a major cardiovascular complication in people with type 2 diabetes (T2D), where heart failure with preserved ejection fraction (HFpEF) is the most common presentation. Despite its high prevalence, HF in T2D often remains undiagnosed during its early stages due to nonspecific symptoms and the limitations of conventional diagnostic tools. Epicardial adipose tissue (EAT), a visceral fat depot surrounding the myocardium, has emerged as a mechanistic and clinically relevant contributor to myocardial dysfunction. In T2D, EAT expansion fosters a pro-inflammatory, fibrotic, and metabolically adverse milieu that may directly promote the onset and progression of HF. This perspective synthesizes current translational evidence on the role of EAT in the pathogenesis of HF among individuals with T2D. We highlight diagnostic challenges related to imaging-based quantification and the limited sensitivity of natriuretic peptide-based screening, while emphasizing the potential relevance of emerging biomarkers such as GDF-15, Galectin-3, sST2, LDL particle size, GGT, and soluble low-density lipoprotein receptor-related protein 1 (sLRP1) to enhance early detection and risk stratification. Additionally, therapeutic approaches—including lifestyle modification, SGLT2 inhibitors, and GLP-1 receptor agonists—are considered for their potential to modulate EAT volume and reduce cardiovascular risk. Advancing knowledge on EAT biology and its circulating biomarkers holds promise to refine HF risk stratification and support translational efforts toward precision cardiometabolic care.