Katarzyna Bergmann

Background: Recent studies have indicated that serum calprotectin, a marker of inflammation, is associated with obesity and disorders of glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum calprotectin and cardiometabolic risk factors in presumably healthy young adults. Methods: The study enrolled 118 (61 females, 57 males) non-obese, normoglycemic, subjects aged 25–40 years, selected from the general population among participants of the diabetes preventive screening program in 2014–2015. Basic anthropometric measurements and the following laboratory tests were performed on all participants: glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), calprotectin and adiponectin. Results: The serum calprotectin concentration was significantly higher in men compared to women (p = 0.016), and in overweight subjects (p < 0.001) and those with abdominal obesity (p < 0.001), compared to lean individuals. Serum calprotectin was positively correlated with body mass index (BMI), waist circumference, HbA1c, hs-CRP, insulin, HOMA-IR and triglycerides, and negatively with HDL-cholesterol and adiponectin. In the univariable logistic regression analysis, overweight (OR = 2.529; p = 0.015), abdominal obesity (OR = 3.217; p = 0.006), hs-CRP > 1 mg/L (OR = 5.00; p < 0.001), HOMA-IR > 2.0 (OR = 4.394; p < 0.001), and HbA1c > 32 mmol/mol (OR = 2.166; p = 0.021) were significant predictors of increased calprotectin concentration (≥540.8 ng/mL; ≥median). However, in models adjusted for sex, BMI and hs-CRP, the significant association remained only for increased HbA1c and HOMA-IR values. Conclusions: Association of serum calprotectin with overweight, hs-CRP and laboratory indicators of glucose metabolism and insulin resistance suggest its significance as a laboratory biomarker of initial metabolic impairment.

Background: Recent studies suggest that erythroferrone (ERFE), an iron-regulating protein whose primary role is to inhibit hepcidin synthesis, may affect glucose and lipid metabolism, and its serum concentration is reduced in obese and diabetic individuals. The aim of this study was to evaluate the association of ERFE concentration with selected cardiometabolic risk factors in apparently healthy young adults. Methods: This preliminary study consisted of 122 (63 females, 59 males) normoglycemic, non-smoking subjects aged 25–40 years. In all participants, anthropometric measurements and the following laboratory tests were performed: fasting plasma glucose, glycated hemoglobin (HbA1c) and serum iron, lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), ERFE and hepcidin. Results: The serum ERFE concentration was significantly lower in men compared to women (p = 0.009) and in subjects who were overweight (p < 0.001) and had abdominal obesity (p < 0.001). ERFE showed significant negative correlations with body mass index, waist–hip ratio, HbA1c, CRP, insulin, HOMA-IR and triglycerides. In the logistic regression analysis, ERFE was significantly associated with being overweight (OR = 0.051; p = 0.004), abdominal obesity (OR = 0.372; p < 0.001), HOMA-IR ≥ 2.0 (OR = 0.584; p = 0.013), CRP > 1 mg/L (OR = 0.648; p = 0.020) and triglycerides (OR = 0.521; p = 0.033). A relevant predominance in the prevalence of cardiometabolic risk factors was observed in subjects with ERFE levels in the first tertile (2.19 ng/mL). Conclusions: Serum ERFE is inversely associated with being overweight, increased waist circumference, CRP, and markers of insulin resistance and lipid abnormalities, suggesting its potential relevance as a marker of early cardiometabolic risk in apparently healthy young adults.

Background: Low but detectable cardiac troponin (cTn) concentrations may reflect cardiovascular (CV) risk in a primary prevention setting. Using previously described thresholds for CV risk stratification, we assessed the influence of sex and cardiometabolic risk factors on the concentrations of high-sensitivity cTn in presumably healthy subjects. Methods: The prospective study included 597 presumably healthy individuals (313 women, 284 men). In all participants, hs-cTnI, hs-cTnT, lipid profile, C-reactive protein, glycated hemoglobin, estimated GFR (eGFR) and B-type naturetic peptide (BNP) were measured. Subjects were categorized into two groups of CV risk, based on hs-cTn non sex-specific cut-off of 5.0 ng/L. For hs-cTnI, sex-specific cut-off values were also used: ≥4.0 ng/L for females and ≥6.0 ng/L for males. Results: Increased CV risk, indicated by hs-cTn concentrations ≥ 5.0 ng/L, was significantly associated with age > 40 years, male sex, obesity and BNP concentrations ≥ 35 ng/L. Using the same 5.0 ng/L threshold, hs-TnT classified approximately twice as many individuals into the CV subgroup compared to hs-cTnI, particularly in males (31% vs. 13%, respectively). After applying sex-specific cut-offs for hs-cTnI, the proportion of females and males with increased risk became similar (8% vs. 9%, respectively). In contrast, using non-sex-specific cut-offs for hs-cTnI resulted in a proportion of 6% for females and 13% for males. BNP and eGFR had significant impact on CV risk stratification using sex-specific cut-offs for hs-cTnI. Conclusions: Our findings suggest the necessity of using sex-specific cut-offs for hs-cTn as a cardiovascular risk marker, in addition to other cardiometabolic factors, in the general population.

Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to advanced liver fibrosis (ALF). We evaluated the diagnostic accuracy of a novel Liver Fibrosis Risk Index (LFRI) in MAFLD subjects using transient elastography (TE) as the reference method for liver fibrosis measurement and then the diagnostic performance of a new two-step non-invasive algorithm for the detection of ALF risk in MAFLD, using Fibrosis-4 (FIB-4) followed by LFRI and comparing it to the reference algorithm based on FIB-4 and TE. We conducted a prospective study on 104 MAFLD European adult subjects. All consenting subjects underwent TE and measurements of FIB-4 and LFRI. For FIB-4 and TE, validated cut-offs were used. An ROC analysis showed that LFRI diagnosed severe fibrosis with moderate accuracy in MAFLD subjects with a negative predictive value above 90%. Using the new algorithm with LFRI thresholds recommended by the manufacturer, the number of subjects classified into ALF risk groups (low, intermediate, or high) differed significantly when compared with the reference algorithm (p = 0.001), with moderate agreement between them (weighted kappa (95% CI) = 0.59 (0.41–0.77)). To improve the performance of the LFRI-based algorithm, we modified cut-off points based on ROC curves obtained by dividing the study population according to the reference algorithm and observed no difference between algorithms (p = 0.054) in categorizing ALF risk, with a slight increase in the total agreement (weighted kappa (95% CI) = 0.63 (0.44–0.82)). Our findings suggest that using the novel LFRI as a second-line test may represent a potential alternative for liver fibrosis risk stratification in MAFLD patients; however, modified cut-offs are needed to optimize its performance.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD)—a new definition for non-alcoholic fatty liver disease—reflects the impact of metabolic abnormalities on liver function. We assessed the diagnostic accuracy of biomarker-based scores for prediction of MAFLD in apparently healthy children. Methods: This study included 144 children aged 9–11. MAFLD was recognized in 14 girls and 29 boys. Anthropometric indices, glycemia, insulin resistance, lipid profile, enzymes (ALT, AST, GGT, ALP), CRP, N-terminal propeptide of type I procollagen (P1NP) and collagen type I C-telopeptide (CTX-1) levels were measured. Fatty liver and hepatic steatosis index (FLI, HSI) and potential indicators of liver fibrogenesis: P1NP/ALP, P1NP/ALPxALT, P1NP/ALPxCRP were calculated. Results: P1NP/ALPxALT and P1NP/ALPxCRP were significantly higher in subjects with MAFLD. FLI was a good, significant predictor of MAFLD occurrence, regardless of sex. In boys, P1NP/ALPxCRP was a comparable predictor as CRP (OR 1.14 vs. 1.17; p < 0.001). P1NP/ALPxCRP had better discrimination capability in boys (AUC = 0.79; p < 0.001). However, the use of this algorithm did not improve discriminatory power in comparison to CRP (AUC = 0.81; p < 0.001), but gave a better sensitivity for MAFLD prediction (86% vs. 59%). Conclusions: We suggest that P1NP/ALPXCRP is a reliable tool for MAFLD prediction in routine pediatric practice.

To assess the determinants of lipid parameters in primary care patients without diagnosed cardiovascular disease (CVD), a cross-sectional study was conducted during 2018–2019 with a total of 200 patients. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), small, dense LDL (sdLDL-C), and lipoprotein (a) (Lp(a)). Predictors of elevated and adequately controlled lipid parameters were assessed with logistic regression analysis. Older age was related to higher risk of TC ≥ 6.2 mmol/L [OR 1.03 (95% CI 1.0–1.05)], sdLDL-C ≥ 1.0 mmol/L [OR 1.05 (95% CI 1.0–1.1)], and decreased risk of Lp(a) ≥ 50 mg/dL [OR 0.97 (95% CI 0.94–0.99)]. Patients with diabetes mellitus (DM) had increased probability of TG ≥ 2.25 mmol/L [OR 3.77 (95% CI 1.34–10.6)] and Lp(a) ≥ 50 mg/dL [OR 2.97 (1.34–6.10)] as well as adequate control of TG and Lp(a). Higher material status was related to lower risk of TC ≥ 6.2 mmol/L [OR 0.19 (95% CI 0.04–0.82)] and LDL-C ≥ 3.6 mmol/L [OR 0.33 (95% CI 0.12–0.92)]. High BMI was related to increased [OR 1.14 (95% CI 1.02–1.29)], and female gender [OR 0.33 (95% CI 0.12–0.96)] and hypertension [OR 0.29 (95% CI 0.1–0.87)] to decreased risk of TG ≥ 2.25 mmol/L [OR 1.14 (95% CI 1.02–1.29)]. Taking lipid-lowering drugs (LLD) was associated with LDL-C < 2.6 mmol/L [OR 2.1 (95% CI 1.05–4.19)] and Lp(a) < 30 mg/dL [OR 0.48 (95% CI 0.25–0.93)]. Physical activity was related to LDL-C < 2.6 mmol/L [OR 2.02 (95% CI 1.02–3.98)]. Higher abdominal circumference was associated with decreased risk of TG < 1.7 mmol/L [OR 0.96 (95% CI 0.93–0.99)]. Elevated lipid parameters were related to age, gender, material status, BMI, history of DM, and hypertension. Adequate control was associated with age, education, physical activity, LLD, history of DM, and abdominal circumference.

Elevated liver enzyme activity may be associated with metabolic syndrome (MetS); however, it is not included in the MetS definition for children. Postprandial changes in the levels of biochemistry tests are related to manifestations of metabolic abnormalities. We assessed the association between fasting and postprandial liver enzymes levels with MetS and elevated hemoglobin A1c (HbA1c) in children aged 9–11. The study included 51 girls and 48 boys, all presumably healthy. In all participants’ anthropometric indices, fasting glucose, insulin, lipid profile and HbA1c were measured. Enzymes, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were assayed in fasting and postprandial states. Individuals were divided into subgroups: with (MetS(+): n = 26); without MetS (MetS(−): n = 73); with HbA1c levels ≤ 5.3% (n = 39); and ≥5.7% (n = 11). Elevated fasting GGT levels were found in 23% of MetS(+) children and rarely in MetS(−) children; increased postprandial GGT was noted in 35% of MetS(+) individuals. Postprandial GGT changes tend to predict MetS (OR = 1.16; p = 0.092). Increased fasting ALT was found rarely in MetS(+) children, but did not occur in MetS(−) children. HbA1c ≥ 5.7% occurred rarely and neither fasting ALT nor GGT were related to elevated HbA1c. However, postprandial change of ALT was a good positive predictor of increased HbA1c (OR = 1.33; p = 0.021). Postprandial GGT performs better as an indicator of metabolic syndrome occurrence, and instead postprandial ALT may predict prediabetes in prepubertal children.

Angiopoietin-like proteins ANGPTL3 and ANGPTL8 have been shown to inhibit lipoprotein lipase, and thus regulate triglyceride level in the circulation. Whether the regulation of lipid metabolism by ANGPTLs is affected by the menopausal status remains unclear. We aimed to assess the relationships between serum ANGPTL3 and ANGPTL8 and atherogenic biomarkers in presumably healthy women during ageing. The study group included 94 women of whom 31 were premenopausal (PRE ≤ 40 years) and 37 were postmenopausal (POST ≥ 52 years). Atherogenic lipid and non-lipid biomarkers and ANGPTLs (ANGPTL3, ANGPTL8) were assayed in serum samples. TG/HDL-C index, non-HDL-cholesterol, remnant cholesterol concentrations, and BMI were calculated. Median levels of ANGPTL3 and concentrations of lipid biomarkers were significantly higher in POST comparing to PRE but ANGPTL8 levels were not different. In PRE, ANGPTL8 levels correlated significantly with TG and TG/HDL-C index while there were no correlations between ANGPTL3 and these biomarkers. In POST both ANGPTLs correlated with TG, sdLDL-C, and TG/HDL-C. ANGPTL8 and sd-LDL-C were the most significant predictors of early triglyceride elevation > 100 mg/dL (1.13 mmol/L) in the whole group and POST whereas the prediction power of ANGPTL3 was negligible in the whole group and non-significant in the subgroups. We demonstrated a significant positive correlation of ANGPTL3 with age category which predisposes to postmenopause. Despite the increase in ANGPTL3 level with ageing the ANGPTL3/ANGPL8 ratio was maintained. In conclusion, ANGPTL8 predicts the early triglyceride elevation better than ANGPTL3, especially in postmenopausal women. The association of ANGPTL3 with triglyceride levels is weaker than ANGPTL8 and depends on menopausal status. We suggest that the choice for the best efficient treatment of dyslipidemia with new inhibitors of angiopoietin-like proteins may depend on the menopausal status.