The Influence of Lifestyle on Male Fertility in the Context of Insulin Resistance-Identification of Factors That Influence Semen Quality.

Background: Male fertility is known to have been negatively influenced by the progress of civilization. Another condition whose incidence has been on the increase for the same reason is insulin resistance (IR). In addition, men increasingly often resign from the pursuit of active forms of leisure, preferring more sedentary ones. Considering these trends, this aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in men with and without the condition. A further aim was to select those lifestyle factors that would make it possible to predict the level of male fertility, especially when IR is concerned. Methods: This study was performed in a group of 73 participants, divided into groups based on their insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. In addition, relevant anthropometric measurements were taken and tests related to glucose metabolism and semen quality were carried out. On the basis of these data, statistical tests were performed to establish or disprove relationships between lifestyle choices and semen quality, as measured my sperm motility. Results: The results of this study highlighted the associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of IR was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. Conclusions: This study underscores the negative impact of modern civilization's lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. This study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of IR.

The Effect of Laparoscopic Sleeve Gastrectomy on the Course of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients during One Year of Follow Up.

BACKGROUND: Morbid obesity co-exists with non-alcoholic fatty liver disease in up to 90% of cases. Laparoscopic sleeve gastrectomy leads to a reduction in body mass and thus may improve the course of non-alcoholic fatty liver disease. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy on the resolution of non-alcoholic fatty liver disease. METHODS: The study included 55 patients with non-alcoholic fatty liver disease who underwent laparoscopic sleeve gastrectomy at a tertiary institution. The analysis consisted of preoperative liver biopsy, abdominal ultrasound, weight loss parameters, Non-Alcoholic Fatty Liver Fibrosis Score and selected laboratory parameters. RESULTS: Before the surgery, 6 patients were diagnosed with grade 1 liver steatosis, 33 patients with grade 2 and 16 patients with grade 3. One year after the surgery, only 21 patients had features of liver steatosis at ultrasound. All weight loss parameters showed statistically significant changes during the observation; the median percentage of total weight loss was 31.0% (IQR: 27.5; 34.5) with p = 0.0003, the median percentage of excess weight loss was 61.8% (IQR: 52.4; 72.3) with p = 0.0013 and the median percentage of excess body mass index loss was 71.0% (IQR: 61.3; 86.9) with p = 0.0036 12 months after laparoscopic sleeve gastrectomy. The median Non-Alcoholic Fatty Liver Fibrosis Score at baseline was 0.2 (IQR: -0.8; 1.0) and decreased to -1.6 (IQR: -2.4; -0.4) (p < 0.0001). Moderate negative correlations between Non-Alcoholic Fatty Liver Fibrosis Score and percentage of total weight loss (r = -0.434, p < 0.0001), percentage of excess weight loss (r = -0.456, p < 0.0001) and percentage of excess body mass index loss (r = -0.512, p < 0.0001) were found. CONCLUSIONS: The study supports the thesis that laparoscopic sleeve gastrectomy is an effective method for treatment of non-alcoholic fatty liver disease in patients with morbid obesity.

Immune Response to Vaccination against COVID-19 at Different Second-Dose Intervals and Their Associations with Metabolic Parameters.

Obesity and diabetes are associated with severe outcomes of coronavirus disease (COVID-19). Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven protective against infection and severe COVID-19. However, the immune response of metabolically burdened individuals to the vaccines remains unclear. Thus, we aimed to assess whether the metabolic status of individuals affects their humoral immune responses to the vaccination. Moreover, we evaluated whether the interval between the first two doses influenced antibody concentration. Sixty-seven individuals (21 males, 46 females) were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Fifty-four individuals were vaccinated with the second dose after 3 weeks and 13 after 5 weeks. We measured the antibody titers in all participants during the 19-week follow-up period. Patients diagnosed with COVID-19 were excluded. In the 5-week interval group, a significantly higher level of maximal antibody titers was observed. However, there were no differences in antibody concentrations after 19 weeks and no significant correlation between cardiometabolic factors and humoral response. The elongation of second-dose timing to 5 weeks leads to a higher acute antibody response but does not change long-term levels of antibody titers. Moreover, dysregulation of metabolic parameters does not lead to a diminished immune response to vaccination.

Testing the Utility of Polygenic Risk Scores for Type 2 Diabetes and Obesity in Predicting Metabolic Changes in a Prediabetic Population: An Observational Study.

Prediabetes is an intermediate state of hyperglycemia during which glycemic parameters are above normal levels but below the T2D threshold. T2D and its precursor prediabetes affect 6.28% and 7.3% of the world's population, respectively. The main objective of this paper was to create and compare two polygenic risk scores (PRSs) versus changes over time (Δ) in metabolic parameters related to prediabetes and metabolic complications. The genetics of 446 prediabetic patients from the Polish Registry of Diabetes cohort were investigated. Seventeen metabolic parameters were measured and compared at baseline and after five years using statistical analysis. Subsequently, genetic polymorphisms present in patients were determined to build a T2D PRS (68 SNPs) and an obesity PRS (21 SNPs). Finally, the association among the two PRSs and the Δ of the metabolic traits was assessed. After a multiple linear regression with adjustment for age, sex, and BMI at a nominal significance of (p < 0.05) and adjustment for multiple testing, the T2D PRS was found to be positively associated with Δ fat mass (FM) (p = 0.025). The obesity PRS was positively associated with Δ FM (p = 0.023) and Δ 2 h glucose (p = 0.034). The comparison of genotype frequencies showed that AA genotype carriers of rs10838738 were significantly higher in Δ 2 h glucose and in Δ 2 h insulin. Our findings suggest that prediabetic individuals with a higher risk of developing T2D experience increased Δ FM, and those with a higher risk of obesity experience increased Δ FM and Δ two-hour postprandial glucose. The associations found in this research could be a powerful tool for identifying prediabetic individuals with an increased risk of developing T2D and obesity.

Untargeted Metabolomics Analysis of the Serum Metabolic Signature of Childhood Obesity.

Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

Metabolomic Profile of Skeletal Muscle and Its Change Under a Mixed-Mode Exercise Intervention in Progressively Dysglycemic Subjects.

Skeletal muscles play an essential role in whole-body glucose homeostasis. They are a key organ system engaged in the development of insulin resistance, and also a crucial tissue mediating the beneficial metabolic effects of physical activity. However, molecular mechanisms underlying both these processes in skeletal muscle remain unclear. The aim of our study was to compare metabolomic profiles in skeletal muscle of patients at different stages of dysglycemia, from normoglycemia through prediabetes to T2D, and its changes under a mixed-mode (strength and endurance) exercise intervention. We performed targeted metabolomics comprising several major metabolite classes, including amino acids, biogenic amines and lipid subgroups in skeletal muscles of male patients. Dysglycemic groups differed significantly at baseline in lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, glutamine, ornithine, and carnosine. Following the exercise intervention, we detected significant changes in lipids and metabolites related to lipid metabolism, including in ceramides and acylcarnitines. With their larger and more significant change over the intervention and among dysglycemic groups, these findings suggest that lipid species may play a predominant role in both the pathogenesis of type 2 diabetes and its protection by exercise. Simultaneously, we demonstrated that amino acid metabolism, especially glutamate dysregulation, is correlated to the development of insulin resistance and parallels disturbances in lipid metabolites.

The Response of Mitochondrial Respiration and Quantity in Skeletal Muscle and Adipose Tissue to Exercise in Humans with Prediabetes.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. METHODS: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. RESULTS: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. CONCLUSIONS: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues.

Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects.

Multiple mechanisms have been suggested to confer to the pathophysiology of metabolic syndrome (MetS), however despite great interest from the scientific community, the exact contribution of each of MetS risk factors still remains unclear. The present study aimed to investigate molecular signatures in peripheral blood of individuals affected by MetS and different degrees of obesity. Metabolic health of 1204 individuals from 1000PLUS cohort was assessed, and 32 subjects were recruited to four study groups: MetS lean, MetS obese, "healthy obese", and healthy lean. Whole-blood transcriptome next generation sequencing with functional data analysis were carried out. MetS obese and MetS lean study participants showed the upregulation of genes involved in inflammation and coagulation processes: granulocyte adhesion and diapedesis (p < 0.0001, p = 0.0063), prothrombin activation pathway (p = 0.0032, p = 0.0091), coagulation system (p = 0.0010, p = 0.0155). The results for "healthy obese" indicate enrichment in molecules associated with protein synthesis (p < 0.0001), mitochondrial dysfunction (p < 0.0001), and oxidative phosphorylation (p < 0.0001). Our results suggest that MetS is related to the state of inflammation and vascular system changes independent of excess body weight. Furthermore, "healthy obese", despite not fulfilling the criteria for MetS diagnosis, seems to display an intermediate state with a lower degree of metabolic abnormalities, before they proceed to a full blown MetS.

The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.

PURPOSE: Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. MATERIALS AND METHODS: The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. RESULTS & CONCLUSIONS: There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.

Sex-Specific Glucose Homeostasis and Anthropometric Responses to Sleeve Gastrectomy in Obese Patients.

Bariatric surgery rapidly and effectively treats obesity and its comorbidities like dysregulated glucose homeostasis. Despite the sex-balanced incidence of obesity in most human populations, women have sought this intervention more frequently than men. However, as the number of bariatric surgeries rapidly rises, it is increasingly urgent to understand how sex-specific differences may emerge in metabolic and anthropometric parameters. Hundred fifty-four obese patients (47% men and 53% women) from the Bialystok Bariatric Surgery Study underwent sleeve gastrectomy and were measured for 25 parameters at baseline (immediately prior to surgery) and at four follow-up visits over one year. We used generalized linear mixed models to detect sex-specific differences in the time series of responses parameters. Unlike most previous studies with older cross-sections of men than women, our cohort was age-matched, and men were less healthy at baseline. Of parameters that showed a significant cohort-wide (across-sex) response, 14 (56%) also showed sex-specific responses with men improving more than women. In particular, men remitted in diabetes symptoms more strongly, rapidly, and durably than women. Taken together, our results indicate that men may benefit more from sleeve gastrectomy and that this difference in improvement may be related to more progressed morbidity prior to surgery independent of age.

Clusters of Glycemic Response to Oral Glucose Tolerance Tests Explain Multivariate Metabolic and Anthropometric Outcomes of Bariatric Surgery in Obese Patients.

Glycemic responses to bariatric surgery are highly heterogeneous among patients and defining response types remains challenging. Recently developed data-driven clustering methods have uncovered subtle pathophysiologically informative patterns among patients without diabetes. This study aimed to explain responses among patients with and without diabetes to bariatric surgery with clusters of glucose concentration during oral glucose tolerance tests (OGTTs). We assessed 30 parameters at baseline and at four subsequent follow-up visits over one year on 154 participants in the Bialystok Bariatric Surgery Study. We applied latent trajectory classification to OGTTs and multinomial regression and generalized linear mixed models to explain differential responses among clusters. OGTT trajectories created four clusters representing increasing dysglycemias that were discordant from standard diabetes diagnosis criteria. The baseline OGTT cluster increased the predictive power of regression models by over 31% and aided in correctly predicting more than 83% of diabetes remissions. Principal component analysis showed that the glucose homeostasis response primarily occurred as improved insulin sensitivity concomitant with improved the OGTT cluster. In sum, OGTT clustering explained multiple, correlated responses to metabolic surgery. The OGTT is an intuitive and easy-to-implement index of improvement that stratifies patients into response types, a vital first step in personalizing diabetic care in obese subjects.

Efficacy of family history, genetic risk score, and physical activity in assessing the prevalence of type 2 diabetes.

INTRODUCTION: Environmental and genetic factors play an important role in the development of type 2 diabetes (T2D). One of the most important lifestyle factors is a low level of physical activity (PA), but no studies have explicitly compared the amount of variation in diabetes prevalence explained by variation in PA compared with the amount explained by genetic variation. OBJECTIVES: We examined associations between PA and patients stratified by the levels of genetic susceptibility to T2D and the prevalence of the disease. PATIENTS AND METHODS: We assessed the level of PA and family history (FH) of T2D in first­degree relatives as well as calculated the genetic risk score (GRS). We examined associations of PA, GRS, and FH with the prevalence of T2D among 1195 individuals enrolled in the 1000 Polish Longitudinal University Study (1000­PLUS) by stratifying the sample according to GRS, FH, and PA. RESULTS: We found that FH, in contrast to GRS, was positively associated with a higher prevalence of T2D (23.4% in patients with positive FH [FH+], 11.6% in those with negative [FH-]; P <0.001), with the association being stronger in men than in women. The prevalence of T2D was slightly lower among physically active individuals in the FH- group (10.6% in high PA vs 14.7% in low PA) as well as in the FH+ group (19.2% in high PA vs 34.0% in low PA), but the differences were not significant. Similar results were found for high and low GRSs. CONCLUSIONS: We confirmed that PA is significantly associated with glucose homeostasis parameters and T2D prevalence, and that this association may be stronger in individuals who are more genetically predisposed to diabetes.

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans.

PURPOSE: The interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization. METHODS: We genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake. RESULTS: We found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024). CONCLUSIONS: We have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.

The Role of Muscle Decline in Type 2 Diabetes Development: A 5-Year Prospective Observational Cohort Study.

The major risk factors of T2DM (type 2 diabetes mellitus) development are still under investigation. We evaluate the possible risk factors associated with type 2 diabetes (T2DM) in adult subjects during a five-year prospective cohort study. We recruited 1160 subjects who underwent oral glucose tolerance test, anthropometric measurements, and body composition and body fat distribution analysis at a baseline visit and again at follow-up after approximately five years. The conclusions of this study are based on observation of 219 subjects who attended both the first and follow-up visits. The fasting serum insulin was measured, and HOMA-IR (homeostatic model assessment of insulin resistance) was calculated. During the follow-up period, T2DM was diagnosed in 7.4% of participants, impaired fasting glucose in 37.7%, and impaired glucose tolerance in 9.3%. Logistic regression models, adjusted for age, were constructed. The changes in glucose concentration, visceral fat tissue content, insulin resistance, and %loss of muscle mass were chosen as the potential predictors for T2DM development. A set of independent variables was extracted. The constructed feature set comprised change in HOMA-IR (OR (odds ratio) = 1.01, p < 0.01) and change in %loss of muscle mass (OR = 0.84, p < 0.03). With an aim to validate the prediction capability using the selected attributes, a support vector machine classifier and leave-one-out cross-validation procedure was applied, yielding 92.78% classification accuracy. Our results show the correlation between the %loss of muscle mass and T2DM development in adults, independent of changes in insulin resistance.

Microangiopathy in Naifold Videocapillaroscopy and Its Relations to sE- Selectin, Endothelin-1, and hsCRP as Putative Endothelium Dysfunction Markers among Adolescents with Raynaud's Phenomenon.

The aim of this study was to analyze the relationship between the qualitative abnormalities on nailfold videocapillaroscopy (NVC), and the concentrations of selected biomarkers (sE-selectin, endothelin-1, high-sensitivity c-reactive protein (hsCRP)) and lipid metabolism parameters in children and adolescents with Raynaud's phenomenon (RP). Raynaud's phenomenon, to assess whether nailfold capillary changes may reflect the degree of systemic blood vessel abnormalities. The study group included 66 patients (34 undifferentiated-uRP and 32 secondary-sRP) aged 6-19 years and the control group. In both groups, NVC was performed and the selected biomarkers were measured (sE-selectin, endothelin-1, hsCRP) and lipid profile. Endothelin-1, sE-selectin and hsCRP concentrations in patients from both RP groups were significantly higher; concentration of HDL fraction was significantly lower compared with the control group. The analysis of multiple linear regression demonstrated that megacapillaries most strongly determine the sE-selectin value (p = 0.04) and hsCRP (p = 0.03). Both the total cholesterol and low-density lipoprotein (LDL) fraction concentrations were determined by the presence of avascular areas (p = 0.02). In conclusion, specific pathologic NVC changes were associated with higher endothelial damage biomarkers concentration and adverse changes in the lipid profile.

First-trimester irisin and fetuin-A concentration in predicting macrosomia.

Objective: We investigated the diagnostic value of first-trimester adipokines and placental markers in predicting macrosomia. Methods: Out of 328 women recruited during the prenatal diagnosis between 11th and 13th week of pregnancy and subjected to follow up until delivery, we selected 26 women who gave birth to macrosomic babies and 34 women who gave birth to normal weight neonates for the evaluation of first trimester serum levels of pregnancy associated plasma protein-A, free ß-human chorionic gonadotropin, placental growth factor (PIGF), and selected adipokines. Results: The mothers of macrosomic infants had higher PIGF (p = .049) and irisin concentrations (p = .00003), and lower fetuin-A levels (p = .0002) than had the mothers of normal weight babies. Newborn's weight correlated positively with maternal irisin (R = 0.454, p = .0003) and negatively with fetuin-A concentrations (R = -0.497, p = .00005). Multiple regression analysis showed that only serum irisin concentration was a significant predictor of birth weight (ß = 0.329, p = .03), explaining 14% of its variability. The sensitivity and the specificity of irisin concentration in predicting macrosomia were 0.769 and 0.794, respectively (AUC = 0.818 [95%CI: 0.708-0.928], p = .00001) with a proposed cut-off value of 1725.4 ng/ml. Conclusions: Our results suggest that mother's irisin may be an early biomarker of macrosomia.

In-and-Out Molecular Changes Linked to the Type 2 Diabetes Remission after Bariatric Surgery: An Influence of Gut Microbes on Mitochondria Metabolism.

Different kinds of gastrointestinal tract modulations known as "bariatric surgery" are actually the most effective treatment for obesity and associated co-morbidities, such as type 2 diabetes (T2DM). The potential causes of those effects have yet to be explained. In our study, we focused on molecular changes evoked by laparoscopic sleeve gastrectomy leading to T2DM remission. Two complementary metabolomics techniques, namely, liquid chromatography coupled with mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS), were used to study those effects in a group of 20 obese patients with T2DM selected from a cohort of 372 obese individuals who underwent bariatric surgery and did not receive anti-diabetic treatment afterward. Modified levels of carnitines, lipids, amino acids (including BCAA) and α- and ß-hydroxybutyric acids were detected. Presented alterations suggest a major role of mitochondria activity in T2DM remission process. Moreover, some of the observed metabolites suggest that changes in gut microbiota composition may also correlate with the tempo of diabetes recovery. Additional analyses confirmed a relationship between biochemical and clinical parameters and the aforementioned metabolites, thereby, highlighting a role of mitochondria and microbes. Our data suggests that there is a previously undescribed relationship between mitochondria and gut microbiota, which changes after the bariatric surgery. More investigations are needed to confirm and explore the observed findings.

Sedentary Lifestyle and Nonspecific Low Back Pain in Medical Personnel in North-East Poland.

INTRODUCTION: The sedentary lifestyle is defined as prolonged sitting both at work and during leisure time, with energy expenditures of below 600 MET · min/week. The sedentary lifestyle is a well-known predictor of obesity and other components of the metabolic syndrome. The influence of the sedentary lifestyle and associated factors on nsLBP is still being discussed. AIM: The aim of this study was to assess the influence of a sedentary lifestyle and its associated metabolic predictors on the prevalence of nsLBP in nurses and paramedics. MATERIALS AND METHODS: The study included 609 participants, aged 30-60 years, who were residents of north-east Poland. Data was collected using a questionnaire (based, in part, on the Nordic Musculoskeletal Questionnaire), and included details of sociodemographic profile, chronic illnesses, and a short version of the International Physical Activity Questionnaire (IPAQ). RESULTS: Nearly half (49.59%) of the respondents reported decreased physical activity, and in the group with recurring nsLBP this figure was 67.59%. Univariate logistic regression modelling found that leading a sedentary lifestyle caused a 3.5-fold increase in the incidence of recurring nsLBP (p<0.001). Excessive coffee consumption significantly increased the likelihood of recurring LBP (OR=16.44, 95% CI: 8.55-31.61), and cigarette smoking increased the likelihood of both recurrent and chronic LBP. The likelihood of chronic low back pain was significantly increased by components of metabolic syndrome such as high blood pressure (over 9-fold), type 2 diabetes (over 3-fold), and hyperlipidemia (over 2-fold) (p<0.001, p<0.001, and p<0.01, respectively). CONCLUSIONS: A sedentary lifestyle significantly increased the incidence of recurring low back pain, while increased physical activity had a significant effect on the presence of chronic low back pain. In the sedentary lifestyle group, conditions classified within metabolic syndrome were found to significantly increase the chances of developing nonspecific low back pain.

CE-MS-based serum fingerprinting to track evolution of type 2 diabetes mellitus.

Development of type 2 diabetes mellitus (T2DM) is preceded by insulin resistance (IR), which may evolve to impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). IFG and IGT are considered as prediabetic states (PD). Prediabetes indicates the high risk for the future development of diabetes, it is estimated that up to 70% of prediabetics eventually develop T2DM. The risk of T2DM development is increased in overweight (OW) and obese (OB) people; however normal weight (NW) individuals also suffer from T2DM. The present study was designed to evaluate whether changes in polar metabolites induced by T2DM evolution are different between NW, overweight and obese individuals. CE-MS serum fingerprinting was performed on 197 serum samples obtained from OW, OB, and NW humans whom were IR, prediabetics, diabetics or with normal glucose homeostasis. Metabolic changes evoked by the progression of T2DM differ between obese, overweight, and normal weight subjects. Based on obtained results several metabolites can be proposed as a promising target to track T2DM evolution; BCAA in OW and NW humans, lysine in OB, while acetylcarnitine and methionine independently on body mass index. Validation of obtained results on larger population is required.

The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.

Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.