Monika Puzianowska-Kuźnicka

Functional polymorphisms of the leptin and leptin receptor genes are associated with longevity and with the risk of myocardial infarction and of type 2 diabetes mellitus.

INTRODUCTION Longevity is commonly associated with good health and with delayed onset of age-related diseases with usually benign course. Leptin (LEP) significantly affects metabolism and numerous functions of the organism. To find out if extreme longevity and its phenotype are associated with genetic variants of leptin and leptin receptor (LEPR) genes, we analysed the frequencies of the -2548 G/A and +19 G/A LEP, as well as the K109R, Q223R, and K656N LEPR polymorphisms in centenarians and in control groups. MATERIAL AND METHODS The frequencies of the LEP and LEPR polymorphisms were tested by restriction fragment length polymorphism in 128 centenarians, 414 young controls (Y), 226 myocardial infarction (MI) patients, and 190 type 2 diabetes mellitus (DM2) patients. RESULTS The GG genotype of the -2548 G/A LEP polymorphism was significantly more common in centenarians than in the Y, MI and DM2 groups (p = 0.048, p = 0.003, p = 0.049, respectively). In addition, the AA genotype of the K109R LEPR polymorphism was significantly less frequent in centenarians than in the Y, MI, and DM2 groups (p = 0.026, p = 0.013, and p = 0.001, respectively). CONCLUSIONS We suggest that the leptin pathway plays a role in the regulation of longevity, possibly by modulating the risk of development of MI and of DM2.

ADIPOQ -11377C>G Polymorphism Increases the Risk of Adipokine Abnormalities and Child Obesity Regardless of Dietary Intake.

Objective: The aim of the present study was to verify whether selected functional single nucleotide polymorphisms in LEP, LEPR, and ADIPOQ loci are associated with the development of obesity and serum levels of the respective adipokines in prepubertal white children with obesity. Methods: Frequencies of −2548G>A LEP (rs7799039), Q223R (rs1137101) and K656N (rs8129183) LEPR, and −11377C>G (rs266729) and −11426A>G (rs16861194) ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism in 101 obese (standard deviation score [SDS]-body mass index [BMI] >2) and 67 normal-weight (SDS-BMI <−1 + 1>) children. Serum adipokine concentrations were measured using the enzyme-linked immunosorbent assay method. Results: The GC/GG genotypes of −11377C>G ADIPOQ polymorphism were associated with a higher risk of obesity (P = 0.022, odds ratio 2.08 [95% confidence interval 1.11–3.90]). Individuals carrying the GG genotype had a higher leptin/total adiponectin ratio by 25% than CC homozygotes (Ptrend = 0.05). In the multivariate linear regression model, we found differences among particular genotypes of this polymorphism in concentrations of high molecular weight (HMW) adiponectin (Ptrend = 0.043) and HMW/total adiponectin ratio (Ptrend = 0.048), with the lowest values in GG homozygotes. Positive correlations between SDS-BMI and dietary reference intake percentage were observed in individuals homozygous for allele C (r = 0.403, P = 0.01) and CG heterozygotes (r = 0.428, P = 0.004). No significant correlations between both parameters were found in the GG homozygotes. Conclusions: Among the analyzed polymorphisms, only −11377C>G ADIPOQ single nucleotide polymorphism was associated with obesity during the prepubertal period. Adipokine abnormalities coexisting with the lack of relations between SDS-BMI and dietary intake may predict a higher risk of future obesity-related disorders in obese children carrying the GG genotype than in those with other genotypes.

The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling.

Abstract Background: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. Materials and methods: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR. Results: The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3 mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for ‘latent inflammation’ proved to be hs-CRP and IL-6 serum levels. In the case of ‘nutritional status’, important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant. Conclusion: The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.

Complementary Effects of Genetic Variations in LEPR on Body Composition and Soluble Leptin Receptor Concentration after 3-Month Lifestyle Intervention in Prepubertal Obese Children

In obese individuals, weight loss might be affected by variants of the adipokine-encoding genes. We verified whether selected functional single nucleotide polymorphisms in LEP, LEPR and ADIPOQ are associated with changes in serum levels of the respective adipokines and weight loss in 100 prepubertal obese (SDS-BMI > 2) Caucasian children undergoing lifestyle intervention. Frequencies of the -2548G > A LEP, Q223R LEPR, K656N LEPR, -11377C > G and -11426A > G ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism. Serum adipokine and soluble leptin receptor (sOB-R) concentrations were measured using the ELISA method. Among the analyzed polymorphisms, only LEPR polymorphisms were associated with changes of SDS-BMI or sOB-R concentrations in children after therapy. Carriers of the wild-type K665N and at least one minor Q223R allele had the greatest likelihood of losing weight (OR = 5.09, p = 0.006), an increase in sOB-R (ptrend = 0.022) and decrease in SDS-BMI correlated with the decrease of fat mass (p < 0.001). In contrast, carrying of the wild-type Q223R and at least one minor K665N allele were associated with a decrease in sOB-R concentrations and a decrease in SDS-BMI correlated with a decrease in fat-free mass (p = 0.002). We suggest that the combination of different LEPR variants, not a single variant, might determine predisposition to weight loss in the prepubertal period.

Prevalence of diabetes in Poland in the years 2010–2014

Introduction. Each year diabetes affects larger and larger number of people. Despite this fact, the number of people suffering from diabetes in Poland is not known precisely. In order to assess this prevalence, the thesis aims at assessing the prevalence of diabetes in the years 2010–2014 in the total Polish population by using the databases of the National Health Fund. Material and methods. In the period from 1st January 2010 until 31st December 2014 patients were distinguished according to PESEL (Personal Identification) numbers: 1. for whom health care providers have indicated diabetes-related ICD-10 codes as the main cause of the medical intervention in billing reports; 2. who had got their prescriptions filled for any hypoglycemic agents or for glucose meter test strips. The number of patients recorded as diabetes patients according to the ICD-10 code and the number of patients who had their prescriptions filled for hypoglycemic agents or test strips were assessed. On the basis of these data the prevalence of diabetes (percentage of people with diabetes in a given year or a percentage of people who had got their prescriptions filled for hypoglycemic agents or test strips in relation to the general population) in respective years and an average prevalence rate for respective voivodeships were assessed. Results. The average percentage of people with diabetes in the years 2010–2014 were found to be 4.47% (± 0.09%). This percentage has gradually increased in the consecutive years from 4.39% in 2010 to 4.61% in 2014. The average percentage of people who had got their prescriptions filled for diabetes related medicines or glucose meter test strips amounted to 5.88% in the years 2010–2014. The largest percentage of people with diabetes was in Silesian Voivodeship and amounted to 5.5% (± 0.1%), the second consecutive voivodeship was Łódź with 5.0% (± 0.2%) of people with diabetes and Opole Voivodeship on the third place with 4.9% (0.1%) inhabitants with diabetes. The smallest percentage of people with diabetes was noted in Warmian-Masurian Voivodeship — 3.5% (± 0.1%) and Subcarpathian Voivodeship — 3.6% (± 0.2%). Conclusions. 1. Average diabetes prevalence rate in Poland in the years 2010–2014 amounted to 4.47% (the assessment was carried out on the basis of the number of people recorded by the National Health Fund as patients with diabetes) or 5.88% (assessment on the basis of the number of people who got their prescriptions filled for reimbursable hypoglycemic agents or glucose meter test strips). 2. Diabetes prevalence in Poland increases in the consecutive years. 3. Prevalence of diabetes varies among voivodeships. (Clin Diabet 2015; 4, 6: 232–237)

Paraoxonase 1 activity and level of antibodies directed against oxidized low density lipoproteins in a group of an elderly population in Poland - PolSenior study.

UNLABELLED The aim of this study was to assess two factors influencing the amount of oxidized LDL-paraoxonase 1 (PON1) activity and the level of anti-oxidized LDL antibodies (anti-ox LDL) in a large group of elderly individuals in Poland. The effects of cognitive status, hypertension and metabolic syndrome and of selected serum lipids and inflammation indicators on PON1 activity and anti-ox LDL level were also examined. The investigated population consisted of 3154 individuals aged 65 and more - participants of the population-based PolSenior project. PON1 arylesterase activity was determined spectrophotometrically, anti-ox-LDL antibodies using ELISA method. PON1 activity significantly decreased with advancing age, was lower in males than in females and decreased in persons with impaired cognition. Individuals with hypertension and high lipid levels showed higher PON1 activity. Lower PON1 activity was related to higher level of inflammation indicators - hsCRP and IL-6. The significant association of PON1 activity with age, HDL-C, LDL-C, sex and IL-6 was confirmed in multivariate analysis. Anti-ox LDL antibodies level was significantly higher in the two oldest subgroups of males. It was significantly lower in males than in females. It was decreased in persons with higher serum triglycerides. No relationship of anti-ox LDL level with cognition, hypertension, metabolic syndrome, inflammation indicators and serum lipid levels was observed. In some persons very high levels of anti-ox LDL were stated, most frequently in the oldest persons, particularly in men. CONCLUSION Both investigated antioxidant factors - PON1 activity and anti-ox LDL level, could play an important role in aging.

NGS Reveals Molecular Pathways Affected by Obesity and Weight Loss-Related Changes in miRNA Levels in Adipose Tissue

Both obesity and weight loss may cause molecular changes in adipose tissue. This study aimed to characterize changes in adipose tissue miRNome in order to identify molecular pathways affected by obesity and weight changes. Next generation sequencing (NGS) was applied to identify microRNAs (miRNAs) differentially expressed in 47 samples of visceral (VAT) and subcutaneous (SAT) adipose tissues from normal-weight (N), obese (O) and obese after surgery-induced weight loss (PO) individuals. Subsequently miRNA expression was validated by real-time PCR in 197 adipose tissues and bioinformatics analysis performed to identify molecular pathways affected by obesity-related changes in miRNA expression. NGS identified 344 miRNAs expressed in adipose tissues with ≥5 reads per million. Using >2 and <−2 fold change as cut-offs we showed that the expression of 54 miRNAs differed significantly between VAT-O and SAT-O. Equally, between SAT-O and SAT-N, the expression of 20 miRNAs differed significantly, between SAT-PO and SAT-N the expression of 79 miRNAs differed significantly, and between SAT-PO and SAT-O, the expression of 61 miRNAs differed significantly. Ontological analyses disclosed several molecular pathways regulated by these miRNAs in adipose tissue. NGS-based miRNome analysis characterized changes of the miRNA profile of adipose tissue, which are associated with changes of weight possibly responsible for a differential regulation of molecular pathways in adipose tissue when the individual is obese and after the individual has lost weight.

Chorobowość z powodu cukrzycy w Polsce w latach 2010–2014

Wstep. Cukrzyca kazdego roku dotyka coraz wiekszej grupy osob. Mimo to liczba osob chorych na cukrzyce w Polsce nie jest dokladnie znana. Aby moc te chorobowośc oszacowac, celem pracy stala sie ocena chorobowości z powodu cukrzycy w latach 2010–2014 w calej populacji polskiej z uzyciem bazy danych Narodowego Funduszu Zdrowia. Material i metody. Od 1 stycznia 2010 roku do 31 grudnia 2014 roku wyodrebniono wedlug numerow PESEL pacjentow: 1. dla ktorych świadczeniodawcy w sprawozdaniach rozliczeniowych ze świadczen jako glowną przyczyne interwencji medycznej wykazali kody ICD-10 związane z cukrzycą; 2. ktorzy zrealizowali recepty na jakikolwiek refundowany lek hipoglikemizujący lub na refundowane testy paskowe do glukometrow. Oceniono liczbe pacjentow wykazanych jako osoby chore na cukrzyce na podstawie kodu ICD-10 oraz liczbe pacjentow, ktorzy zrealizowali recepty na leki hipoglikemizujące lub testy paskowe. Na podstawie tych danych oceniono chorobowośc z powodu cukrzycy (odsetek osob wykazanych jako chore na cukrzyce w danym roku lub odsetek osob, ktore zrealizowaly recepty na leki hipoglikemizujące lub testy paskowe w odniesieniu do populacji ogolnej) w poszczegolnych latach oraz średni wskaźnik chorobowości dla poszczegolnych wojewodztw. Wyniki. Średni odsetek osob wykazanych jako chore na cukrzyce w latach 2010–2014 wyniosl 4,47% (± 0,09%). Odsetek ten w kolejnych latach sukcesywnie wzrastal z 4,39% w 2010 roku do 4,61% w 2014. Średni odsetek osob, ktore zrealizowaly recepty na leki lub paski w latach 2010–2014, wyniosl 5,88%. Najwiekszy średni udzial osob wykazanych jako chore na cukrzyce byl w wojewodztwie śląskim i wynosil 5,5% (± 0,1%), drugim wojewodztwem w kolejności bylo wojewodztwo lodzkie — 5,0% (± 0,2%), a trzecim wojewodztwo opolskie — 4,9% (0,1%). Najmniejszym średnim odsetkiem osob wykazanych jako chore na cukrzyce odznaczaly sie wojewodztwa warminsko-mazurskie — 3,5% (± 0,1%) i podkarpackie — 3,6% (± 0,2%). Wnioski. 1. Średni wskaźnik chorobowości z powodu cukrzycy w Polsce w latach 2010–2014 wyniosl 4,47% (ocena dokonana na podstawie liczby osob wykazanych do NFZ jako chore na cukrzyce) albo 5,88% (ocena na podstawie liczby osob, ktore zrealizowaly recepty na refundowane leki hipoglikemizujące lub paski testowe do glukometrow). 2. Chorobowośc z powodu cukrzycy w Polsce wzrasta w kolejnych latach. 3. Chorobowośc z powodu cukrzycy rozni sie miedzy poszczegolnymi wojewodztwami.