Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

Periodontal disease in gestational and type 1 diabetes mellitus pregnant women

Objective: The present study evaluated the relationship between periodontal disease and its clinical variables in Brazilian non-diabetic pregnant women (C), gestational diabetes mellitus (GDM), or type 1 diabetes mellitus (T1DM). Subjects and methods: A periodontal exam was performed in one hundred and sixty-one pregnant women (GDM:80; T1DM:31; C:50) by a single-blinded calibrated examiner who recorded plaque index (PI), gingival index (GI), bleeding index (BI), gingival margin location (GM), probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and tooth mobility index (MI). The medical variables were age, pregestational body mass index (pre-BMI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA(1c)). Results: The GI, GM, PD, CAL, BOP, and MI were significantly higher (P < 0.01) among GDM and T1DM than for C. The PI was higher in GDM and similar between C and T1DM. The Adjusted Final Model for medical variables to evaluate the effects of groups on periodontal parameters confirmed these results. Conclusions: The presence of periodontal disease was significantly higher in Brazilian diabetic pregnancies (GDM and T1DM) when compared to non-diabetic pregnant women (C). The degree of periodontal disease was similar between the GDM and T1DM groups. Age, pregestational BMI, and HbA(1c) were factors related to CAL development in these two types of diabetes mellitus.

Thiazolidinediones and type 2 diabetes: new drugs for an old disease

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA(1c) and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA(1c) than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.

Effects of physical exercise training in DNA damage and repair - could the difference be in hOGG1 Ser326Cys polymorphism?

Acute physical exercise is associated with increased oxygen consumption, which could result in an increased formation of reactive oxygen species (ROS). ROS can react with several organic structures, namely DNA, causing strand breaks and a variety of modified bases in DNA. Physical exercise training seems to decrease the incidence of oxidative stress-associated diseases, and is considered as a key component of a healthy lifestyle. This is a result of exercise-induced adaptation, which has been associated with the possible increase in antioxidant activity and in oxidative damage repair enzymes, leading to an improved physiological function and enhanced resistance to oxidative stress (Radak et al. 2008). Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is involved in the base excision repair (BER) pathway and encodes an enzyme responsible for removing the most common product of oxidative damage in DNA, 8-hydroxyguanine (8-OH-G). The genetic polymorphism of hOGG1 at codon 326 results in a serine (Ser) to cysteine (Cys) amino acid substitution (Ser326Cys). It has been suggested that the carriers of at least one hOGG1Cys variant allele exhibit lower 8-OH-G excision activity than the wild-type (Wilson et al. 2011). The aim of this study was to investigate the possible influence of hOGG1 Ser326Cys polymorphism on DNA damage and repair activity in response to 16 weeks of combined physical exercise training, in thirty healthy Caucasian men. Comet assay was carried out using peripheral blood lymphocytes and enabled the evaluation of DNA damage, both strand breaks and FPG-sensitive sites, and DNA repair activity. Genotypes were determined by PCR-RFLP analysis. The subjects with Ser/Ser genotype were considered as wild-type group (n=20), Ser/Cys and Cys/Cys genotype were analyzed together as mutant group (n=10). Regarding differences between pre and post-training in the wild-type group, the results showed a significant decrease in DNA strand breaks (DNA SBs) (p=0.002) and also in FPG-sensitive sites (p=0.017). No significant differences were observed in weight (p=0.389) and in lipid peroxidation (MDA) (p=0.102). A significant increase in total antioxidant capacity (evaluated by ABTS) was observed (p=0.010). Regarding mutant group, the results showed a significant decrease in DNA SBs (p=0.008) and in weight (p=0.028). No significant differences were observed in FPG-sensitive sites (p=0.916), in ABTS (p=0.074) and in MDA (p=0.086). No significant changes in DNA repair activity were observed in both genotype groups. This preliminary study suggests the possibility of different responses in DNA damage to physical exercise training, considering the hOGG1 Ser326Cys polymorphism.

Estudo experimental para avaliação da rigidez dos vasos sanguíneos: testes para validação clínica

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de mestre em Engenharia Biomédica.

Estudo comparativo de medição da velocidade da onda de pulso: VasoCheck versus complior

A medição da Velocidade da Onda de Pulso (VOP), enquanto meio complementar de diagnóstico e tratamento das doenças cardiovasculares, é considerada um marcador precoce de compromisso arterial em diversos contextos clínicos. O seu papel consolida-se na prevenção primária da patologia arterial, através da avaliação das propriedades mecânicas dos vasos sanguíneos, nomeadamente, quanto à sua rigidez e distensibilidade. Neste trabalho pretende-se comparar os valores experimentais da VOP obtidos com dois métodos de medição diferentes. Para a obtenção das ondas de pulso, utilizaram-se dois equipamentos não-invasivos que permitem uma avaliação in-vivo das propriedades mecânicas dos vasos sanguíneos. Estes distinguem-se pelo princípio físico em que se baseiam: o Complior usa sensores de pressão, baseando-se no princípio piezoeléctrico e o protótipo do equipamento VasoCheck, desenvolvido no nosso grupo da NMT, usa sensores ópticos de infra-vermelho, baseando-se no princípio fotopletismográfico (FPG). As medições com os dois métodos realizaram-se em ambiente controlado, numa amostra de 42 voluntários dos 20 aos 30 anos de idade, de ambos os sexos, saudáveis e sem diagnóstico cardiovascular associado. Os dados experimentais obtidos com os métodos e sensores acima enunciados foram tratados estatisticamente. Os valores da VOP obtidos com o método FPG mostraram-se consistentes e em boa concordância com os obtidos com o método piezoeléctrico. O método FPG aparenta ser mais rápido na sua utilização. Futuramente, evidencia-se importante repetir a série de medições com os dois métodos numa amostra maior, estendendo-a também a voluntários com diagnóstico cardiovascular conhecido. Com base neste trabalho foi apresentada a comunicação painel “Análise comparativa de dois métodos de medição da Velocidade da Onda de Pulso” na International Conference on Health Technology Assessment and Quality Management 2012, realizada a 3 e 4 de Fevereiro de 2012 na Escola Superior de Tecnologia da Saúde de Lisboa.

Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study).

OBJECTIVE: The associations between inflammation, diabetes and insulin resistance remain controversial. Hence, we assessed the associations between diabetes, insulin resistance (using HOMA-IR) and metabolic syndrome with the inflammatory markers high-sensitive C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand eight hundred and eighty-four men and 3201 women, aged 35-75, participated in this study. METHODS: C-reactive protein was assessed by immunoassay and cytokines by multiplexed flow cytometric assay. In a subgroup of 532 participants, an oral glucose tolerance test (OGTT) was performed to screen for impaired glucose tolerance (IGT). RESULTS: IL-6, TNF-α and hs-CRP were significantly and positively correlated with fasting plasma glucose (FPG), insulin and HOMA-IR. Participants with diabetes had higher IL-6, TNF-α and hs-CRP levels than participants without diabetes; this difference persisted for hs-CRP after multivariate adjustment. Participants with metabolic syndrome had increased IL-6, TNF-α and hs-CRP levels; these differences persisted after multivariate adjustment. Participants in the highest quartile of HOMA-IR had increased IL-6, TNF-α and hs-CRP levels; these differences persisted for TNF-α and hs-CRP after multivariate adjustment. No association was found between IL-1β levels and all diabetes and insulin resistance markers studied. Finally, participants with IGT had higher hs-CRP levels than participants with a normal OGTT, but this difference disappeared after controlling for body mass index (BMI). CONCLUSION: We found that subjects with diabetes, metabolic syndrome and increased insulin resistance had increased levels of IL6, TNF-α and hs-CRP, while no association was found with IL-1β. The increased inflammatory state of subjects with IGT is partially explained by increased BMI.

National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants.

BACKGROUND: Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. METHODS: We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. FINDINGS: In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6-11·2) in men and 9·2% (8·0-10·5) in women in 2008, up from 8·3% (6·5-10·4) and 7·5% (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5%, 11·6-20·1 for men; and 15·9%, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. INTERPRETATION: Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. FUNDING: Bill & Melinda Gates Foundation and WHO.

4B.05: Plasma Lasma copeptin is associated with insulin resistance in a Swiss population-based study

OBJECTIVE: Previous studies suggest that arginine vasopressin may have a role in metabolic syndrome (MetS) and diabetes by altering liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We tested whether plasma copeptin, the stable C-terminal fragment of arginine vasopressin prohormone, was associated with insulin resistance and MetS in a Swiss population-based study. DESIGN AND METHOD: We analyzed data from the population-based Swiss Kidney Project on Genes in Hypertension. Copeptin was assessed by an immunoluminometric assay. Insulin resistance was derived from the HOMA model and calculated as follows: (FPI x FPG)/22.5, where FPI is fasting plasma insulin concentration (mU/L) and FPG fasting plasma glucose (mmol/L). Subjects were classified as having the MetS according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Mixed multivariate linear regression models were built to explore the association of insulin resistance with copeptin. In addition, multivariate logistic regression models were built to explore the association between MetS and copeptin. In the two analyses, adjustment was done for age, gender, center, tobacco and alcohol consumption, socioeconomic status, physical activity, intake of fruits and vegetables and 24 h urine flow rate. Copeptin was log-transformed for the analyses. RESULTS: Among the 1,089 subjects included in this analysis, 47% were male. Mean (SD) age and body mass index were 47.4 (17.6) years 25.0 (4.5) kg/m2. The prevalence of MetS was 10.5%. HOMA-IR was higher in men (median 1.3, IQR 0.7-2.1) than in women (median 1.0, IQR 0.5-1.6,P < 0.0001). Plasma copeptin was higher in men (median 5.2, IQR 3.7-7.8 pmol/L) than in women (median 3.0, IQR 2.2-4.3 pmol/L), P < 0.0001. HOMA-IR was positively associated with log-copeptin after full adjustment (β (95% CI) 0.19 (0.09-0.29), P < 0.001). MetS was not associated with copeptin after full adjustment (P = 0.92). CONCLUSIONS: Insulin resistance, but not MetS, was associated with higher copeptin levels. Further studies should examine whether modifying pharmacologically the arginine vasopressin system might improve insulin resistance, thereby providing insight into the causal nature of this association.

Plasmid DNA damage induced by singlet molecular oxygen released from the naphthalene endoperoxide DHPNO2 and photoactivated methylene blue

To investigate oxidative lesions and strand breaks induction by singlet molecular oxygen (¹O2), supercoiled-DNA plasmid was treated with thermo-dissociated DHPNO2 and photoactivated-methylene blue. DNA lesions were detected by Fpg that cleaves DNA at certain oxidized bases, and T4-endoV, which cleaves DNA at cyclobutane pyrimidine dimers and apurinic/apyrimidinic (AP) sites. These cleavages form open relaxed-DNA structures, which are discriminated from supercoiled-DNA. DHPNO2 or photoactivated-MB treatments result in similar plasmid damage profile: low number of single-strand breaks or AP-sites and high frequency of Fpg-sensitive sites; confirming that base oxidation is the main product for both reactions and that ¹O2 might be the most likely intermediate that reacts with DNA.

Photodynamic DNA damage induced by phycocyanin and its repair in Saccharomyces cerevisiae

In the present study, we analyzed DNA damage induced by phycocyanin (PHY) in the presence of visible light (VL) using a set of repair endonucleases purified from Escherichia coli. We demonstrated that the profile of DNA damage induced by PHY is clearly different from that induced by molecules that exert deleterious effects on DNA involving solely singlet oxygen as reactive species. Most of PHY-induced lesions are single strand breaks and, to a lesser extent, base oxidized sites, which are recognized by Nth, Nfo and Fpg enzymes. High pressure liquid chromatography coupled to electrochemical detection revealed that PHY photosensitization did not induce 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) at detectable levels. DNA repair after PHY photosensitization was also investigated. Plasmid DNA damaged by PHY photosensitization was used to transform a series of Saccharomyces cerevisiae DNA repair mutants. The results revealed that plasmid survival was greatly reduced in rad14 mutants, while the ogg1 mutation did not modify the plasmid survival when compared to that in the wild type. Furthermore, plasmid survival in the ogg1 rad14 double mutant was not different from that in the rad14 single mutant. The results reported here indicate that lethal lesions induced by PHY plus VL are repaired differently by prokaryotic and eukaryotic cells. Morever, nucleotide excision repair seems to play a major role in the recognition and repair of these lesions in Saccharomyces cerevisiae.

Development according to pubertal stage in Brazilian children and adolescents with short-term diabetes

The anthropometric status and metabolic control of 51 recently diagnosed Brazilian schoolchildren with type 1 diabetes (DM1), during the first 5 years of the disease, were compared with those of normal children (60 girls and 132 boys) belonging to the same environmental condition and pubertal stage. Metabolic control was evaluated on the basis of fasting plasma glucose (FPG) and HbA1c levels. The criteria of the National Center for Health Statistics were used for anthropometric evaluation. FPG (205 ± 51 mg/dl for girls vs 200 ± 34 mg/dl for boys) and % above upper normal limit of median HbA1c (1.8% for girls vs 2.5% for boys with diabetes) were not significantly different during follow-up. The Z-score of the last height evaluation was lower in the girls' group (-0.14 vs -0.53, P<0.05). By forward stepwise analysis, the Z-score of the initial height was statistically significant as a determinant factor for height at the end of the study in both girls and boys with DM1. The Z-score of weight at last evaluation was not different from that at diagnosis in either sex. However, analysis according to pubertal stage showed a tendency to a weight increase in the girls. The weight recovery and height loss in girls with DM1 follows the trend of the normal Brazilian population.

Hydrogen peroxide induces a specific DNA base change profile in the presence of the iron chelator 2,2’ dipyridyl in Escherichia coli

Pretreatment of Escherichia coli cultures with the iron chelator 2,2’-dipyridyl (1 mM) protects against the lethal effects of low concentrations of hydrogen peroxide (<15 mM). However, at H2O2 concentrations equal to or greater than 15 mM, dipyridyl pretreatment increases lethality and mutagenesis, which is attributed to the formation of different types of DNA lesions. We show here that pretreatment with dipyridyl (1 mM) prior to challenge with high H2O2 concentrations (≥15 mM) induced mainly G:C→A:T transitions (more than 100X with 15 mM and more than 250X with 20 mM over the spontaneous mutagenesis rate) in E. coli. In contrast, high H2O2 concentrations in the absence of dipyridyl preferentially induced A:T→T:A transversions (more than 1800X and more than 300X over spontaneous mutagenesis for 15 and 20 mM, respectively). We also show that in the fpg nth double mutant, the rpoB gene mutation (RifS-RifR) induced by 20 mM H2O2 alone (20X higher) was increased in 20 mM H2O2 and dipyridyl-treated cultures (110X higher), suggesting additional and/or different lesions in cells treated with H2O2 under iron deprivation. It is suggested that, upon iron deprivation, cytosine may be the main damaged base and the origin of the pre-mutagenic lesions induced by H2O2.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7%) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5% in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): £2.93 mm (RR = 0.54; 95%CI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm² (RR = 0.66; 95%CI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm³ (RR = 0.74; 95%CI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95%CI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): ≤108.8 mg/dL (RR = 0.53; 95%CI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and ofXpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.