Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. Methods: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. Results: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). Conclusions: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.

Background: Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Results: Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL, P = 0.028). There were significant correlations between PTX3 and alanine aminotransferase ( P = 0.018), gamma-glutamyl transferase ( P = 0.005), and neuropathy disability score ( P < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. Conclusions: PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.

Background: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. Methods: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. Results: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. Conclusion: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

Background: Fetuin-A is a multifunctional liver-derived glycoprotein that is associated with insulin resistance and might play a role in the pathogenesis of prediabetes and type 2 diabetes (T2DM). Objective: This study evaluated the relationship of Fetuin-A with metabolic and vascular parameters in patients with prediabetes and T2DM. Materials and methods: total 120 obese patients were included. They were divided into three groups: group 1 – without carbohydrate disturbances, group 2 – with prediabetes and group 3 – with type 2 diabetes mellitus. Results: Higher Fetuin-A serum levels were observed in patients with prediabetes and T2DM compared to those with normoglycemia. Fetuin-A ≥821 mcg/ml increased the risk for T2DM 32-fold. Additionally, we found positive correlations between Fetuin-A, vibration perception threshold and toe-brachial index and a negative correlation with neuropathy disability score. Conclusion: Fetuin-A could be predictive for incidents of prediabetes and T2DM.

Background: Lumican is a small leucine-rich proteoglycan that regulates the assembly of collagen fibers in the extracellular matrix of different tissues. Excess collagen production in the liver is key in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and might contribute to the risk of type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to evaluate the relationship between serum lumican and prediabetes, and other biochemical and clinical parameters in obese subjects with NAFLD. Methods: The study group included 79 subjects with obesity and NAFLD of which 41 had normal carbohydrate tolerance and 38 had prediabetes. Serum lumican was measured by means of enzyme-linked immunosorbent assay. Results: Higher lumican serum levels were found in patients with prediabetes compared with those with normal carbohydrate tolerance (0.117 ± 0.074 vs. 0.080 ± 0.048 ng/mL, P = 0.010) as well as in subjects with metabolic syndrome (MetS) versus those without MetS (0.113 ± 0.071 vs. 0.079 ± 0.048 ng/mL, P = 0.034). There was also a modest positive association between lumican levels and fasting glucose (r = 0.228, P < 0.05). Lumican levels ≥0.07 ng/mL determine a 3.9-fold higher risk of prediabetes (odds ratio: 3.945, 95% confidence interval: 1.518–10.254, P = 0.005). Conclusions: Lumican levels were higher in obese subjects with NAFLD with prediabetes and MetS. Lumican bears an increased risk for prediabetes in the study population.

Background/Objectives: Metabolic syndrome (MetS) is a complex, multifaceted disorder with significant socioeconomic and public health consequences, increasingly acknowledged as a global epidemic. Fibroblast growth factor 21 (FGF-21) is known to play a vital role in metabolic regulation; however, the precise roles and interactions of free fatty acids (FFAs) and insulin in influencing FGF-21 activity under both normal and pathological conditions are not yet fully understood. Meteorin-like protein (Metrnl) is a newly identified adipokine that appears to have the potential to regulate metabolic inflammation, which is a critical pathological factor in obesity and insulin resistance. Additionally, nesfatin-1, which is widely expressed in both central and peripheral tissues, is thought to be involved in various physiological functions beyond appetite control, such as glucose homeostasis, stress response, and cardiovascular health. Recent studies have indicated that sortilin may play a role in the pathophysiology of several metabolic disorders, including type 2 diabetes mellitus. Methods: This investigation was a cross-sectional study involving 200 individuals with obesity, which included both metabolically healthy obese participants and those experiencing obesity along with glycemic disorders. Serum levels of FGF-21, sortilin, Metrnl, and nesfatin-1 were measured using standardized enzyme-linked immunosorbent assay (ELISA) techniques. Results: The results indicated that FGF-21 levels were significantly elevated in patients with metabolic syndrome (p < 0.001), as well as those with insulin resistance (p = 0.009) and dyslipidemia (p = 0.03). Serum Metrnl levels were notably elevated in individuals meeting the criteria for insulin resistance, with a statistical significance of p < 0.001. Additionally, patients experiencing carbohydrate metabolism disorders exhibited significantly higher serum sortilin levels compared to those with normal blood glucose levels, with a p-value of 0.003. Conclusions: This research highlights FGF-21, Metrnl, nesfatin-1, and sortilin as potential biomarkers involved in the development of critical aspects of metabolic syndrome.