To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1 H-NMR) spectroscopy with periodontitis and tooth loss.
A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1 H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing.
While only spurious associations between lipoprotein levels from conventional blood tests were found-that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1 H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity.
Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.

Anhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging evidence suggests that sex differences in immune-inflammatory markers and lipoprotein profiles are associated with anhedonia.
The demographic and clinical data, immune-inflammatory markers (CD3, CD4, and CD8), and lipoprotein profiles [TC, TG, LDL-C, HDL-C, lipoprotein(a) Lp (a)] of 227 patients with unipolar and bipolar depression were collected. The Hamilton Depression Rating Scale (HAMD) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess depression and anhedonia symptoms. Data were analyzed using ANOVA, logistic regression, and receiver operating characteristic curves.
Male patients in the anhedonia group had higher levels of CD3, CD4, and CD8, and lower levels of Lp (a) than the non-anhedonia group, while no significant difference was identified in female patients with and without anhedonia. Logistic regression analysis showed that CD3, CD4, CD8, and Lp (a) levels were associated with anhedonia in male patients. Furthermore, the combination of CD3, CD4, CD8, and Lp (a) had the strongest predictive value for distinguishing anhedonia in male patients than individual parameters.
We identified sex-specific associations between immune-inflammatory markers, lipoprotein profiles, and anhedonia in patients with unipolar and bipolar depression. The combination of CD3, CD4, CD8, and Lp (a) might be a possible biomarker for identifying anhedonia in male patients with unipolar and bipolar depression.

Children with familial hypercholesterolaemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C) concentrations since birth, which increases the risk of cardiovascular disease in adulthood. Arterial injury and stiffness parameters, including carotid intima media thickness (cIMT), pulse wave velocity (PWV) and distensibility (DIST), can be detected early in childhood. We studied the associations between cIMT, PWV and DIST with the lipoprotein profile assessed by proton nuclear magnetic resonance (1H NMR) and with influential variables such as blood pressure (BP) or body mass index (BMI) in children with FH.
In this cross-sectional study, we included 201 children (96 with FH and 105 non-FH controls). Clinical history, physical examination and standard biochemical studies were performed. FH genetic testing was performed when clinically indicated. Carotid ultrasonography and an advanced lipoprotein profile by 1H NMR were performed. Multivariate and classification methods were used. There were no differences between cIMT, PWV and DIST between FH and non-FH children. FH children presented more total LDL and large, medium and small particles. Small LDL particles, BMI and systolic BP determined the presence of pathological IMT in the FH group. LDL size, high-density lipoproteins and very low-density lipoprotein particles together with blood pressure determined the presence of pathological arterial wall elasticity.
Alterations in lipoprotein parameters assessed by are associated with early structural and functional arterial characteristics in children with FH. BMI and BP act as boosting factors. Cardiovascular prevention should start early in children with FH, encompassing all components of a healthy lifestyle.

Abnormal lipid metabolism is associated with gestational diabetes mellitus (GDM) and is observed in neonates with abnormal fetal growth. However, the underlying specific changes in the lipoprotein profile remain poorly understood. Thus, in the present study we used a novel nuclear magnetic resonance (NMR)-based approach to profile the umbilical cord serum lipoproteins. Two-dimensional diffusion-ordered 1H-NMR spectroscopy showed that size, lipid content, number and concentration of particles within their subclasses were similar between offspring born to control (n = 74) and GDM (n = 62) mothers. Subsequent data stratification according to newborn birth-weight categories, i.e., small (n = 39), appropriate (n = 50) or large (n = 49) for gestational age (SGA, AGA and LGA, respectively), showed an interaction between GDM and birth-weight categories for intermediate-density lipoproteins (IDL)-cholesterol content and IDL- and low-density lipoproteins (LDL)-triglyceride content, and the number of medium very low-density lipoproteins (VLDL) and LDL particles specifically in AGA neonates. Moreover, in a 2-year follow-up study, we observed that small LDL particles were independently associated with offspring obesity at 2 years (n = 103). Collectively, our data demonstrate that GDM disturbs triglyceride and cholesterol lipoprotein content across birth-weight categories, with AGA neonates born to GDM mothers displaying a profile more similar to that of adults with dyslipidemia. Furthermore, an altered fetal lipoprotein pattern was associated with the development of obesity at 2 years.

The LipoSEARCH® System is an innovative lipoprotein class analysis method based on gel-permeation high-performance liquid chromatography (HPLC). This system uses a gel permeation column to separate the major lipoprotein subclasses (chylomicron, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein) in serum according to particle size and splits them into two pathways to measure total cholesterol (TC; esterified + unesterified cholesterol) and triglyceride (TG) concentrations simultaneously to obtain chromatograms for each. These chromatograms were analyzed based on the results of the calibration serum by fitting Gaussian curves to profile the 20 lipoprotein subclasses defined in detail. An important assumption of this HPLC system is its simultaneous detection of two pathways to guarantee the accuracy of each analysis. Therefore, in the present study, we investigated the development of an internal standard that can guarantee the simultaneous detection of this system by adding a pigment to the serum. We focused on quinone pigments with absorption at 550 nm, which is the wavelength used for the enzymatic assay of TC and TG concentrations in the system. As a result, we succeeded in producing overlapping pigment peaks that appeared after the analytical chromatograms in two pathways. It is also suggested that the pigment solution as an internal standard is stable in freezing storage and has little effect on the analysis. The developed internal standard is expected to contribute to the accuracy assurance of lipoprotein analysis by this dual-detection HPLC system.

(1) Background: Apolipoprotein E(ApoE) plays a critical role in lipid transport. The specific allele of APOE being expressed is associated with the development of coronary heart disease (CHD), however the specific mechanisms by which ApoE drives disease are unclear. In this study, we investigated the relationship between APOE allele, lipoprotein metabolome, and CHD severity to provide evidence for the efficacy of clinical cholesterol-lowering therapy; (2) Methods: Blood samples were collected from 360 patients with CHD that were actively being treated with statins. The lipoprotein profile, including particle numbers, particle size, and lipoprotein composition concentrates, was measured by nuclear magnetic resonance (NMR) spectroscopy. The severity of CHD was determined by quantifying coronary angiography results using the Gensini scoring system; (3) Results: We found there was no significant difference in low-density lipoprotein cholesterol (LDL-C) levels among ε2+ (ε2 allele carriers, consisting of ε2/ε2 and ε2/ε3 genotypes), ε3 (consisting of ε3/ε3 and ε2/ε4 genotypes), and ε4+ (ε4 allele carriers, consisting of ε3/ε4 and ε4/ε4 genotypes) participants receiving statin treatment. Compared with the ε3 group, patients with the ε2+ genotype showed lower concentrations of total low-density lipoprotein (LDL), small-LDL, and middle-LDL particles, as well as a larger LDL size, higher very low-density lipoprotein (VLDL) composition concentrates, and higher intermediate density lipoprotein (IDL) composition concentrates. The ε4+ group showed higher concentrations of total LDL, small LDL particles, and LDL compositions with smaller LDL size. The higher level of small LDL concentration was associated with a high Gensini score (B = 0.058, p = 0.024). Compared with the ε3 group, the risk of increased branch lesions in the ε2+ group was lower (OR = 0.416, p = 0.027); (4) Conclusions: The specific allele of APOE being expressed can affect the severity of CHD by altering components of the lipoprotein profile, such as the concentration of small LDL and LDL size.

This study aimed to describe the dyslipidemia prevalence and pattern among adult populations from different regions (n = 13) of the Russian Federation (RF). Randomly selected samples (n = 22,258, aged 25-64) were studied according to the ESSE-RF protocol. Lipoprotein parameters were estimated by routine methods. Statistical analyses were performed using R software (v.3.5.1). The overall dyslipidemia prevalence was 76.1% (76.9/75.3% for men/women). In women, total cholesterol (TC) and low-density lipoprotein (LDL)-C levels gradually increased with age (from 4.72 to 5.93 and from 2.76 to 3.79 mmol/L, respectively); in men, they reached a maximum by 45-54 (5.55 and 3.55 mmol/L, respectively) and then decreased. No differences in high-density lipoprotein (HDL)-C in men of different ages were found, but slight decreases in HDL-C and apo AI were observed in women by 55-64 years. No pronounced associations between education and lipid levels in men were observed; higher-educated women showed significantly better lipoprotein profiles. Similar associations between lipids and income level were detected. Women from rural areas had higher TC and triglycerides than urban residents. Regardless of sex, rural residents had higher HDL-C and apo AI, and reduced apo B/apo AI. Conclusion: Information on the peculiarities of dyslipidemia prevalence and lipoprotein profile depending on sex, age, residential place, and socioeconomic status is useful for assessing the global ASCVD risk, and for risk modeling based on national data.

BACKGROUND: Type 2 diabetes mellitus, a rapidly growing epidemic, and its frequently related complications demand global attention. The two factors commonly attributed to the epidemic are genetic factors and environmental factors. Studies indicate that the genetic makeup at an individual level and the environmental aspects influence the occurrence of the disease. However, there is insufficiency in understanding the mechanisms through which the gene mutations and environmental components individually lead to T2DM. Also, discrepancies have often been noted in the association of gene variants and type 2 diabetes when the gene factor is examined as a sole attribute to the disease.
METHODS: In this review initially, we have focused on the proposed ways through which CAPN10, FABP2, GLUT2, TCF7L2, and ENPP1 variants lead to T2DM along with the inconsistencies observed in the gene-disease association. The article also emphasizes on obesity, lipoprotein profile, and nutrition as environmental factors and how they lead to T2DM. Finally, the main objective is explored, the environment-gene-disease association i.e. the influence of each environmental factor on the aforementioned specific gene-T2DM relationship to understand if the disease-causing capability of the gene variants is exacerbated by environmental influences.
CONCLUSIONS: We found that environmental factors may influence the gene-disease relationship. Reciprocally, the genetic factors may alter the environment-disease relationship. To precisely conclude that the two factors act synergistically to lead to T2DM, more attention has to be paid to the combined influence of the genetic variants and environmental factors on T2DM occurrence instead of studying the influence of the factors separately.

Dyslipidemia precedes type 2 diabetes (T2D) and worsens with increasing glucose intolerance. First degree relatives of T2D patients have an increased risk to develop dyslipidemia and glucose intolerance. The aim of the present study was to assess the relation between the development of dyslipidemia and glucose intolerance in first-degree relatives of T2D patients.
Fasting lipoprotein profiles were determined by density gradient ultracentrifugation in T2D patients and their first-degree relatives (42 Caucasians and 33 South Asians), and in 29 normoglycemic controls from non-T2D families. Glucose tolerance, insulin sensitivity index (ISI) and insulin disposition index (DI) were assessed by an extended, frequently sampled oral glucose tolerance test (OGTT), and fractional insulin synthesis rate (FSR) was measured by 13C-leucine enrichment in urinary C-peptide during the OGTT.
Of the first-degree relatives, 40, 16 and 19 had NGT, prediabetes and T2D, respectively. NGT family members had lower plasma HDL-cholesterol (HDLC) (1.34 ± 0.07 vs 1.58 ± 0.06 mmol/L; p = 0.015), HDL2-C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p = 0.021) and HDL3-C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p = 0.043) than controls. HDL2-C levels tended to decrease with increasing glucose intolerance state. In South Asians, buoyant LDL-C levels decreased with increasing glucose intolerance state (p = 0.006). In South Asian families, HDL-C correlated with both ISI and DI (β 0.42; p = 0.04 and β 0.53; p = 0.01, respectively), whereas HDL2-C and HDL3-C levels correlated with DI (β 0.64; p = 0.002 and β 0.57; p = 0.005, respectively). HDL2-C and plasma triglyceride correlated with FSR (β 0.48; p = 0.033 and β -0.50; p = 0.029, respectively).
Low HDL2-C and HDL3-C levels are present in NGT first-degree relatives of T2D patients, and HDL2-C tend to decrease further with increasing glucose intolerance. In South Asian families HDL2-C and HDL3-C levels linked predominantly to deteriorating beta cell function.

Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Studies also suggest that certain dietary behaviours may be cardioprotective. Limited comparative data regarding any dietary score/index-lipoprotein particle subclass associations exist. Thus, our objective was to assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Health Eating Index-2015 (HEI-2015), Mediterranean Diet (MD) and Energy-adjusted Dietary Inflammatory Index (E-DII™) scores and plasma lipids and lipoprotein profiles to test the hypothesis that healthier diet (better quality and more anti-inflammatory) would be associated with a more favourable lipoprotein profile.
This was a cross-sectional study of 1862 men and women aged 46-73 years, randomly selected from a large primary care centre in Ireland. DASH, HEI-2015, MD and E-DII scores were derived from food frequency questionnaires. Lipoprotein subclass particle concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with lipoprotein particle subclasses.
In fully adjusted models, higher diet quality or a more anti-inflammatory diet was associated with less large and medium very low-density lipoprotein (VLDL) (DASH and HEI-2015), intermediate-density lipoprotein (IDL) (DASH, MD and E-DII) and small high-density lipoprotein (HDL) (DASH, HEI-2015 and E-DII) particles. After accounting for multiple testing, relationships with large VLDL (DASH: β = -0.102, p = .037), IDL (DASH: β = -0.089, p = .037) and small HDL (DASH: β = -0.551, p = .014 and E-DII: β = 0.483, p = .019) concentrations persisted.
These findings provide evidence that better diet quality, determined by the DASH score, may be more closely associated with a more favourable lipoprotein particle subclass profile in middle-to older-aged adults than the HEI-2015, MD and E-DII scores. A less pro-atherogenic lipoprotein status may be a potential mechanism underlying the cardioprotective effects of higher dietary quality.