Changes in plasma endocannabinoids concentrations correlate with 18F-FDG PET/MR uptake in brown adipocytes in humans.

Introduction: Recent data suggest a possible role of endocannabinoids in the regulation of brown adipose tissue (BAT) activity. Those findings indicate potential treatment options for obesity. The aim of this study was to evaluate the relationship between plasma endocannabinoids concentrations and the presence of BAT in humans. Methods: The study group consisted of 25 subjects divided into two groups: BAT positive BAT(+), (n = 17, median age = 25 years) and BAT negative BAT(-), (n = 8, median age = 28 years). BAT was estimated using 18F-FDG PET/MR after 2 h of cold exposure. The level of plasma endocannabinoids was assessed at baseline, 60 min and 120 min of cold exposure. Results: In both groups, BAT(+) and BAT(-), during the cooling, we observed a decrease of the same endocannabinoids: arachidonoylethanolamide (AEA), eicosapentaenoyl ethanolamide (EPEA) and oleoyl ethanolamide (OEA) with a much more profound decline in BAT(+) subjects. Statistically significant fall of PEA (palmitoylethanolamide) and SEA (stearoylethanolamide) concentrations after 60 min (FC = 0.7, p = 0.007 and FC = 0.8, p = 0.03, respectively) and 120 min (FC = 0.81, p = 0.004, and FC = 0.9, p = 0.01, respectively) of cooling was observed only in individuals with BAT. Conclusion: We noticed the profound decline of endocannabinoids concentrations in subjects with increased 18F-FDG PET/MR uptake in BAT. Identification of a new molecules related to BAT activity may create a new target for obesity treatment.

Optimization of a GC-MS method for the profiling of microbiota-dependent metabolites in blood samples: An application to type 2 diabetes and prediabetes.

Changes in serum or plasma metabolome may reflect gut microbiota dysbiosis, which is also known to occur in patients with prediabetes and type 2 diabetes (T2DM). Thus, developing a robust method for the analysis of microbiota-dependent metabolites (MDMs) is an important issue. Gas chromatography with mass spectrometry (GC-MS) is a powerful approach enabling detection of a wide range of MDMs in biofluid samples with good repeatability and reproducibility, but requires selection of a suitable solvents and conditions. For this reason, we conducted for the first time the study in which, we demonstrated an optimisation of samples preparation steps for the measurement of 75 MDMs in two matrices. Different solvents or mixtures of solvents for MDMs extraction, various concentrations and volumes of derivatizing reagents as well as temperature programs at methoxymation and silylation step, were tested. The stability, repeatability and reproducibility of the 75 MDMs measurement were assessed by determining the relative standard deviation (RSD). Finally, we used the developed method to analyse serum samples from 18 prediabetic (PreDiab group) and 24 T2DM patients (T2DM group) from our 1000PLUS cohort. The study groups were homogeneous and did not differ in age and body mass index. To select statistically significant metabolites, T2DM vs. PreDiab comparison was performed using multivariate statistics. Our experiment revealed changes in 18 MDMs belonging to different classes of compounds, and seven of them, based on the SVM classification model, were selected as a panel of potential biomarkers, able to distinguish between patients with T2DM and prediabetes.

Different Protein Sources Enhance 18FDG-PET/MR Uptake of Brown Adipocytes in Male Subjects.

BACKGROUND: The unique ability of brown adipocytes to increase metabolic rate suggests that they could be targeted as an obesity treatment. OBJECTIVE: The objective of the study was to search for new dietary factors that may enhance brown adipose tissue (BAT) activity. METHODS: The study group comprised 28 healthy non-smoking males, aged 21-42 years old. All volunteers underwent a physical examination and a 75 g oral glucose tolerance test (75g-OGTT). Serum atrial and brain natriuretic peptide (ANP, BNP), PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16) and eukaryotic translation initiation factor 4E (eIF4E) measurements were taken, and 3-day food intake diaries were completed. Body composition measurements were assessed using dual-energy X-ray absorptiometry (DXA) scanning and bioimpedance methods. An fluorodeoxyglucose-18 (FDG-18) uptake in BAT was assessed by positron emission tomography/magnetic resonance (PET/MR) in all participants after 2 h cold exposure. The results were adjusted for age, daily energy intake, and DXA lean mass. RESULTS: Subjects with detectable BAT (BAT(+)) were characterized by a higher percentage of energy obtained from dietary protein and fat and higher muscle mass (p = 0.01, p = 0.02 and p = 0.04, respectively). In the BAT(+) group, animal protein intake was positively associated (p= 0.04), whereas the plant protein intake negatively correlated with BAT activity (p = 0.03). Additionally, the presence of BAT was inversely associated with BNP concentration in the 2 h of cold exposure (p = 0.002). CONCLUSION: The outcomes of our study suggest that different macronutrient consumption may be a new way to modulate BAT activity leading to weight reduction.

Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer.

The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for DEMs was found for miR-146-5p (AUC = 0.770) expression, indicating possible clinical applicability in PTC diagnosis. The combination of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) showed an AUC of 0.841. Validation by real-time quantitative polymerase chain reactions (qRT-PCRs) confirmed our findings. The introduction of an miRNA diagnostic panel based on the results of our study may help to improve therapeutic decision making for questionable cases. The use of miRNAs as biomarkers of PTC may become an aspect of personalized medicine.

PET/MRI-Evaluated Activation of Brown Adipose Tissue via Cold Exposure Impacts Lipid Metabolism.

Although brown adipose tissue (BAT) is considered to play a protective role against obesity and type 2 diabetes, the mechanisms of its activation and associations with clinical parameters are not well described. Male adults underwent a 2 h cold exposure (CE) to activate BAT and, based on the results of PET/MRI performed after the CE, were divided into BAT(+) and BAT(-) groups. During the CE procedure, blood samples were collected and alterations in plasma metabolome in both groups were investigated using LC-MS. Additionally, associations between clinical factors and BAT were examined. Moreover, levels of glucose, insulin, leptin, TNF-α, FGF21, and FABP4 were assessed in serum samples. In the BAT(+) group, levels of LPC(17:0), LPE(20:4), LPE(22:4), LPE(22:6), DHA, linoleic acid, and oleic acid increased during CE, whereas levels of sphinganine-phosphate and sphingosine-1-phosphate decreased. Levels of LPE(O-18:0), 9-HpODE, and oleic acid were elevated, while the level of LPE(20:5) was reduced in BAT(+) compared to BAT(-) subjects. AUCs of LPC(18:2), LPC(O-18:2)/LPC(P-18:1), and SM(d32:2) negatively correlated with BAT. In the BAT(+) group, the concentration of FABP4 during and after CE was decreased compared to the basal level. No alterations were observed in the BAT(-) group. In conclusion, using untargeted metabolomics, we proved that the plasma metabolome is affected by cold-induced BAT activation.

PET/MRI-evaluated brown adipose tissue activity may be related to dietary MUFA and omega-6 fatty acids intake.

An investigation of new ways to activate brown adipose tissue (BAT) is highly valuable, as it is a possible tool for obesity prevention and treatment. The aim of our study was to evaluate the relationships between dietary intake and BAT activity. The study group comprised 28 healthy non-smoking males aged 21-42 years. All volunteers underwent a physical examination and 75-g OGTT and completed 3-day food intake diaries to evaluate macronutrients and fatty acid intake. Body composition measurements were assessed using DXA scanning. An FDG-18 PET/MR was performed to visualize BAT activity. Brown adipose tissue was detected in 18 subjects (67% normal-weight individuals and 33% overweight/obese). The presence of BAT corresponded with a lower visceral adipose tissue (VAT) content (p = 0.04, after adjustment for age, daily kcal intake, and DXA Lean mass). We noted significantly lower omega-6 fatty acids (p = 0.03) and MUFA (p = 0.02) intake in subjects with detected BAT activity after adjustment for age, daily average kcal intake, and DXA Lean mass, whereas omega-3 fatty acids intake was comparable between the two groups. BAT presence was positively associated with the concentration of serum IL-6 (p = 0.01) during cold exposure. Our results show that BAT activity may be related to daily omega-6 fatty acids intake.

An Association between Diet and MC4R Genetic Polymorphism, in Relation to Obesity and Metabolic Parameters-A Cross Sectional Population-Based Study.

The melanocortin-4 receptor (MC4R) gene harbours one of the strongest susceptibility loci for obesity and obesity-related metabolic consequences. We analysed whether dietary factors may attenuate the associations between MC4R genotypes and obesity and metabolic parameters. In 819 participants genotyped for common MC4R polymorphisms (rs17782313, rs12970134, rs633265, and rs135034), the anthropometric measurements, body fat content and distribution (visceral and subcutaneous adipose tissue, VAT and SAT, respectively), and blood glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides concentrations, and daily macronutrient intake were assessed. ANOVA or Kruskal-Wallis tests were used, and multivariate linear regression models were developed. We observed that the CC genotype carriers (rs17782313) presented higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations when they were stratified to the upper quantiles of protein intake. An increase in energy derived from proteins was associated with higher BMI (Est. 5.74, R2 = 0.12), body fat content (Est. 8.44, R2 = 0.82), VAT (Est. 32.59, R2 = 0.06), and VAT/SAT ratio (Est. 0.96, R2 = 0.05). The AA genotype carriers (rs12970134) presented higher BMI, body fat, SAT and VAT, fasting blood glucose, triglycerides and total cholesterol concentrations. An increase in energy derived from proteins by AA carriers was associated with higher VAT (Est.19.95, R2 = 0.06) and VAT/SAT ratio (Est. 0.64, R2 = 0.05). Our findings suggest that associations of the common MC4R SNPs with obesity and its metabolic complications may be dependent on the daily dietary intake, which may open new areas for developing personalised diets for preventing and treating obesity and obesity-related comorbidities.

Oxidative stress and radioiodine treatment of differentiated thyroid cancer.

It is hypothesized that the oxidative stress level in thyroid cancer patients is additionally upregulated by radioactive iodine (RAI) treatment, that may exert an important impact on future health concerns. In our study, we evaluated the oxidative stress level changes using the measurement of malondialdehyde (MDA) concentration in patients with differentiated thyroid cancer (DTC) undergoing RAI treatment. Considering the results obtained in the study group, the serum levels of MDA in DTC patients were significantly higher compared to the healthy subjects (p < 0.05). The MDA concentration was significantly higher on the third day after RAI (p < 0.001) and significantly lower one year after RAI (p < 0.05) in DTC patients compared to the baseline concentration. Moreover, the redox stabilization after RAI treatment in patients with DTC during a year-long observation was demonstrated. Accordingly, an increased oxidative stress impact on the related biochemical parameters reflecting the health conditions of the DTC patients was determined. Our study showed that increased oxidative stress reflected by MDA measurements in DTC patients is further enhanced by RAI, but this effect is no longer observed one year after the therapy.

Dosimetry during adjuvant 131I therapy in patients with differentiated thyroid cancer-clinical implications.

The activity of radioiodine (131I) used in adjuvant therapy for thyroid cancer ranges between 30 mCi (1.1 GBq) and 150 mCi (5.5 GBq). Dosimetry based on Marinelli's formula, taking into consideration the absorbed dose in the postoperative tumour bed (D) should systematise the determination of 131I activity. Retrospective analysis of 57 patients with differentiated thyroid cancer (DTC) after thyreidectomy and adjuvant 131I therapy with the fixed activity of 3.7 GBq. In order to calculate D from Marinelli's formula, the authors took into account, among other things, repeated dosimetry measurements (after 6, 24, and 72 h) made during scintigraphy and after administration of the therapeutic activity or radioiodine. In 75% of the patients, the values of D were > 300 Gy (i.e. above the value recommended by current guidelines). In just 16% of the patients, the obtained values fell between 250 and 300 Gy, whereas in 9% of the patients, the value of D was < 250 Gy. The therapy was successful for all the patients (stimulated Tg < 1 ng/ml and 131I uptake < 0.1% in the thyroid bed in follow-up examination). Dosimetry during adjuvant 131I therapy makes it possible to diversify the therapeutic activities of 131I in order to obtain a uniform value of D.

Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis.

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.

Mass spectrometry-based determination of lipids and small molecules composing adipose tissue with a focus on brown adipose tissue.

Adipose tissue has been the subject of research for a very long time. Many studies perform a comprehensive analysis of different types of adipose tissue with an emphasis on brown adipose tissue. Mass spectrometry-based approaches are particularly useful in the exploration not only of the metabolic composition of adipose tissue but also its function. In the presented review, a complex and critical overview of publications devoted to the analysis of adipose tissue by means of mass spectrometry was performed. Detailed investigation of analytical aspects related to either untargeted or targeted analysis of adipose tissue was performed, leading to the formation of a collection of hints at the available analytical methods. Moreover, a profound analysis of the metabolic composition of brown adipose tissue was performed. Brown adipose tissue metabolome was characterized on structural and functional levels, providing information about its exact metabolic composition but also connecting these molecules and placing them into biochemical pathways. All our work resulted in a very broad picture of the analysis of adipose tissue, starting from the analytical aspects and finishing on the current knowledge about its composition.

Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study.

Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

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.

Enhancing the efficacy of 131I therapy in non-toxic multinodular goitre with appropriate use of methimazole: an analysis of randomized controlled study.

PURPOSE: It is possible to raise the rate of the uptake of 131I in the thyroid gland (RAIU) by increasing the endogenous TSH level through appropriate use of methimazole (MMI) prior to 131I therapy. The purpose of this paper is to assess the impact of pre treatment with MMI on the efficacy of 131I therapy in non-toxic multinodular goitre (NMG). METHODS: Thirty-one patients with NMG received 131I treatment in order to reduce the volume of the thyroid (TVR). Those in group 1 (n = 16) were administered 10 mg of methimazole for 6 weeks. Four days after its discontinuation, they received 131I. Patients in group 2 (n = 15) were given a placebo instead of MMI. The therapeutic activity of 131I was constant (800 MBq) and was repeated every 6 months. Treatment was discontinued when TVR reached <40 ml. RESULTS: In group 1, RAIU increased approximately twofold. Ten patients from group 2 and four patients from group 1 received further doses of 131I. The median of time until TVR decreased below 40 ml was 9 months [6-12 months] and 18 months [14-22 months] in group 2. At 2 years after the 131I therapy, the occurrence of hypothyroidism did not differ significantly (36% in group 1 and 33% in group2, p = 0.074). CONCLUSIONS: Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of 131I administration, without an increase in the incidence of post-treatment hypothyroidism.

The interplay between muscle mass decline, obesity, and type 2 diabetes.

The world's population is progressively becoming older, and age­related conditions are a major public health concern. A worrying phenomenon worldwide is the increasing obesity among aging societies, which occurs in parallel with a higher prevalence of sarcopenia in older populations. As a result of the combination of these 2 states, new medical conditions, such as sarcopenic obesity, have recently become a public health concern. Data from the literature indicate a higher risk of metabolic syndrome, type 2 diabetes (T2D), and atherosclerosis among patients with sarcopenic obesity than the risk associated with simple obesity or sarcopenia alone. The mechanisms underlying sarcopenic obesity are multifactorial. There is an interplay between low­grade inflammation, insulin resistance, hormonal changes, a sedentary lifestyle, eating habits, and aging. The aim of this review is to summarize the available data regarding the definition, epidemiology, and pathways that lead to sarcopenic obesity, as well as treatment strategies.

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.

Efficacy of 99mTc-DTPA SPECT/CT in diagnosing Orbitopathy in graves' disease.

BACKGROUND: The most frequently used methods of assessing Graves' orbithopathy (GO) include: Clinical Activity Score (CAS), ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI). There exists another, slightly forgotten, imaging method: single-photon emission computed tomography (SPECT) with the use of diethylenetriaminepentaacetic acid tagged with 99mTc (99mTc-DTPA). These days it is possible to conduct a SPECT examination fused with a CT scan (SPECT/CT), which increases the diagnostic value of the investigation. The aim of this paper is to evaluate the usefulness of 99mTc-DTPA SPECT/CT in diagnosing Graves orbitopathy, as compared with other methods. METHODS: Twenty-three patients with suspected active (infiltrative-edematous) Graves' orbithopathy were included in the study. Each patient underwent a CAS, an MRI, and a SPECT/CT. The obtained results were analysed statistically, with the assumed statistical significance of p < 0.05. RESULTS: The SPECT/CT and MRI were found to have the highest sensitivity: 0.93 each. The SPECT/CT had the highest specificity: 0.89. MRI and CAS had lower values: 0.78 and 0.56, respectively. The occurrence of an active form of GO had no impact on the exacerbation of exophthalmos or the thickness of the oculomotor muscles. CONCLUSIONS: The 99mTc-DTPA SPECT/CT method provides a very good tool for assessing the active form of GO and can, alongside the MRI scan, be used as a referential diagnostic procedure in GO.

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.

[Differences in dietary habits and food preferences of adults depending on the age]. / Róznice w nawykach i preferencjach iywieniowych osob doroslych w zaleznosci od wieku.

BACKGROUND: Changes in the structure and functioning of the body occur with age. Also nutrition is continually modified. Eating habits may affect favorably or unfavorably on the process of aging and the functioning of various tissues, organs and the whole body. OBJECTIVES: The purpose of the study was to evaluate dietary habits and food preferences of patients in different age groups. In the studied groups also body mass index (BMI) and body fat content were analyzed. MATERIAL AND METHOD: 237 people (133 women and 104 men, age 18-79 years) were examined. The participants completed questionnaires of the frequency of food consumption and food preferences. The height, weight, body mass index (BMI), the percentage of body fat (BIA) were also measured. For statistical analysis the assessment of correlation Spearman's rank order and nonparametric ANOVA rank Kruskal-Wallis were used. RESULTS: With age, the frequency of milk (p < 0,05) and cheese (p < 0,05) consumption decreased whereas consumption of cottage cheese increased (p < 0,05). Increased consumption of offal (p < 0,05), salt (p < 0,05) and coffee (p< 0, 05) was also noted. With age, the respondents preferred animal fats (p < 0.05) and vegetable fats (p < 0.05). The frequency of butter consumption decreased (p < 0.05) and consumption of vegetable fats increased (p < 0,05). The consumption of brown rice (p < 0,05), whole wheat pasta (p < 0,05) and cereals (p < 0,05) was reduced whereas the consumption of groats (p < 0,05) potatos (p < 0,05) and fruits (p < 0,05) increased. The decreased desire (p < 0,05) and frequency of nuts / almonds consumption (p < 0,05) were noted. With age, the BMI and percentage of body fat were increasing (p < 0,05, R = 0,39, p < 0,05, R = 0,31, respectively). CONCLUSIONS: Taste preferences and dietary habits vary depending on age and may be one of the elements affecting the increase in BMI, body fat content, bone mass loss and increased risk of metabolic disorders. The observed changes in dietary habits can contribute to the development of dyslipidemia, glucose dysmetabolism and arterial hypertension, especially in the presence of overweight and obesity.