Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucose-lowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

Depressive symptomatology, weight status and obesogenic risk among Australian adolescents: a prospective cohort study

OBJECTIVES: Adolescence is a period of increased risk for mental health problems and development of associated lifestyle risk behaviours. This study examined cross-sectional and longitudinal associations between obesogenic risk factors, weight status, and depressive symptomatology in a cohort of Australian adolescents.

DESIGN: Prospective cohort study.

SETTING: The study used repeated measures data from the Australian Capital Territory (ACT) It's Your Move project, an Australian community-based obesity prevention intervention. Intervention effect was non-significant therefore intervention and comparison groups were combined in this study.

PARTICIPANTS: Total sample was 634 secondary school students (female n=338, male n=296) with mean age 13 years (SD=0.6) at baseline (2012) and 15 years (SD=0.6) at follow-up (2014) recruited from 6 government secondary schools in the ACT.

PRIMARY AND SECONDARY OUTCOMES MEASURES: Primary outcome was depressive symptomatology measured by Short Mood and Feelings Questionnaire. Secondary outcomes were weight status, physical activity, screen time and diet related measures.

RESULTS: Increased physical activity was associated to lower depressive symptomatology among males (OR=0.35, p<0.05). Sweet drink (OR=1.15, p<0.05) and takeaway consumption (OR=1.84, p<0.05) were associated with higher levels of depressive symptomatology among females at follow-up. Males who were classified as overweight or obese at baseline, and remained so over the study period, were at increased risk of depressive symptomatology at follow-up (b=1.63, 95% CI 0.33 to 2.92). Inactivity among males over the 2-year study period was predictive of higher depressive symptomatology scores at follow-up (b=2.55, 95% CI 0.78 to 4.32). For females, those who increased their consumption of takeaway foods during the study period were at increased risk for developing depressive symptomatology (b=1.82, 95% CI -0.05 to 3.71).

CONCLUSIONS: There are multiple, probably complex, relationships between diet, physical activity and outcomes of obesity and mental health as well as between the outcomes themselves. Healthier diets and increased physical activity should be foundations for healthier body weight and mental health.

Long-term cost-effectiveness of weight management in primary care

Background:  As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively.

Methods:  Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain.

Results:  Mean weight changes in Counterweight attenders was −3 kg and −2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was £59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was ‘dominant’ (cost-saving) under ‘base-case scenario’, where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was £2017 where background weight gain was limited to 0.5 kg/year, and £2651 at 0.3 kg/year. Under a ‘best-case scenario’, where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained ‘dominant’ with background weight gains 1 kg, 0.5 kg or 0.3 kg/year.

Conclusion:  Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

Mudanças no hábito de fumar e ganho de peso gestacional : um estudo de coorte em capitais brasileiras

Objetivo: Avaliar a influência de mudanças no hábito de fumar sobre o ganho de peso gravídico materno. Métodos: Foram entrevistadas 5.564 gestantes com 20 anos ou mais, sem diabetes mellitus prévio em serviços de pré-natal geral de seis capitais brasileiras, entre 1991 e 1995, e acompanhamos, através de revisão de prontuários, as gestações até o parto, identificando 4.000 gestantes com peso pré-gravídico relatado, peso medido no terceiro trimestre, hábito de fumar e época de sua eventual modificação, quando disponíveis. Resultados: Entre as gestantes ex-fumantes (915, 23% do total), 240 (26%) pararam de fumar durante a gravidez. A mediana de cigarros/dia das que continuaram fumantes (717, 18%) foi reduzida de 10 para 5 após o início da gravidez. Após ajustar para idade, escolaridade, cor da pele, IMC pré-gravídico, paridade e centro clínico, as ex-fumantes ganharam 1.030 g (IC95% 590 a 1.460) a mais que as nunca fumantes, sendo maior a diferença (1.540, IC95% 780 a 2.300 g) nas que pararam após a concepção. O ganho do peso na gravidez se correlacionou, tanto em fumantes quanto em ex-fumantes, com o número de cigarros diminuídos na gravidez. Conclusão: Diminuir ou parar de fumar na gravidez, embora importante para uma gestação saudável, é fator de risco para ganho de peso materno.

Dietas de proteína reduzida e de diferentes digestabilidades suplementadas com aminoácidos sintéticos para frangos de corte

O conceito de proteína ideal adquiriu grande importância, devido à necessidade de maximizar o uso dos aminoácidos para a deposição de proteína corporal. O objetivo deste trabalho foi avaliar a formulação de rações com teor reduzido de PB suplementadas com aminoácidos sintéticos e de diferentes digestibilidades. Foram realizados dois experimentos (exp) utilizando frangos de corte machos das linhagens Ross (exp I) e Cobb (exp 11),no período de 3 a 6 semanas. No exp I foram testadas rações à base de milho e farelo de soja com quatro níveis de PB (20,8; 19,7; 18,6 e 17,5%). No exp 11,além dos tratamentos com os mesmos níveis de PB do exp I e digestibilidade padrão (DP), compostos principalmente por milho e farelo de soja, também foram testados dois tratamentos com dietas contendo 20,8 e 17,5% de PB e alta digestibilidade (AD), à base de milho, farelo de soja, amido de milho e proteína isolada de soja. Nos dois experimentos o ganho de peso, a conversão alimentar e o rendimento de cortes nobres foram negativamente afetados pela redução da PB dietética (P<0,05). Entretanto, as respostas de digestibilidade da matéria seca e digestibilidade da matéria orgânica, a retenção relativa de PB e a energia metabolizável aparente corrigida para nitrogênio foram superiores nas aves alimentadas com as dietas de baixos níveis de PB (P<0,05), mas não suficientes para compensar as perdas no desempenho. Não houve efeito da dieta AD sobre as respostas avaliadas, talvez em função das características físicas dos ingredientes utilizados.

Efeito de polimorfismos no gene LEP na expressão da leptina em adipócitos de bovinos de corte

Os caracteres produtivos são normalmente influenciados por muitos fatores, sendo difícil determinar todos os locos envolvidos em um fenótipo específico. Por isso, a seleção animal tem se baseado principalmente em uma estimativa direta ou indireta do fenótipo. A leptina é um importante regulador do metabolismo energético, da adiposidade e da reprodução. E por desempenhar diferentes funções, pode ser considerado um bom gene candidato para o estudo de associações entre marcadores moleculares e a eficiência reprodutiva ou ganho de peso. Em várias espécies, têm sido descritos diversos polimorfismos no gene da leptina, influenciando o ganho de peso, a reprodução, e outras características produtivas. Em bovinos, o STR IDVGA51 e o SNP LEPSau3A1, foram descritos por afetarem a performance reprodutiva, os alelos IDVGA51*181 e LEPSau3A1*2 estando associados a um aumento no intervalo entre partos de 79 e 81 dias, respectivamente, e os STRs BMS1074 e BM1500 afetam o ganho de peso, em vacas, no pós-parto: os alelos BMS1074*151 e BM1500*135 reduzindo e aumentando, respectivamente, o ganho de peso diário. Para confirmar o efeito ou não destes alelos na expressão do gene da leptina, este trabalho comparou os níveis de mRNA de leptina em animais portadores e não portadores dos alelos IDVGA51*181, LEPSau3A1*2, BMS1074*151 e BM1500*135, com os objetivos de: 1. Verificar as distribuições genotípicas e alélicas dos marcadores IDVGA51, BMS1074, BM1500 e LEPSau3A1, em uma amostra de 137 bovinos da raça Brangus-Ibagé, provenientes da Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA-Pecuária Sul, Bagé-RS). 2. Identificar, no rebanho, animais portadores e não portadores dos alelos IDVGA51*181, LEPSau3A1*2, BMS1074*151 ou BM1500*135, previamente descritos como associados à eficiência reprodutiva e ganho de peso. 3. Avaliar os animais, criados em campo nativo, com pastagem natural, quanto à sua condição corporal. 4. Realizar procedimento cirúrgico, para obtenção de amostras de tecido adiposo subcutâneo e omental. 5. Dosar os níveis de mRNA de leptina nos adipócitos destes dois tecidos, através do método quantitativo em tempo real (Real-Time RT-PCR), comparando a expressão do gene LEP entre indivíduos portadores e não portadores dos alelos de predisposição a ganho de peso e desempenho reprodutivo.

Ação Sacietogênica de um inibidor de tripsina da semente de tamarindo (Tamarindus indica L.)

The seeds are excellent sources of proteinase inhibitors and have been highlighted owing to various applications. Among these applications are those in effect on food intake and weight gain that stand out because of the increasing number of obese individuals. This study evaluated the effects of trypsin inhibitor present in the seed of tamarind (Tamarindus indica L.) reduction in weight gain, biochemical and morphological alterations in Wistar rats. For this, we partially purified a trypsin inhibitor tamarind seed. This inhibitor, ITT2 at a concentration of 25 mg / kg body weight, over a period of 14 days was able to reduce food intake in rats (n = 6) by approximately 47%, causing a reduction in weight gain approximately 70% when compared with the control group. With the evaluation of the in vivo digestibility was demonstrated that the animals lost weight due to satiety, presented by the reduction of food intake, since there were significant differences between true digestibility for the control group (90.7%) and the group treated with inhibitor (89.88%). Additionally, we checked the deeds of ITT2 on biochemical parameters (glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, gamma glutamyl transferase albumin, globulin, total protein and C-reactive protein) and these, when assessed in the study groups showed no statistically significant variations. We also evaluate the histology of some organs, liver, stomach, intestine, and pancreas, and showed no changes. And to evaluate the effect of trypsin inhibitor on food intake due to the satiety is regulated by cholecystokinin (CCK) were measured plasma levels, and it was observed that the levels of CCK in animals receiving ITT2 were significantly higher ( 20 + 1.22) than in animals receiving only solution with casein (10.14 + 2.9) or water (5.92 + 1.15). Thus, the results indicate that the effect caused ITT2 satiety, reducing food intake, which in turn caused a reduction in weight gain in animals without causing morphological and biochemical changes, this effect caused by the elevation of plasma levels CCK

Aspectos da biologia reprodutiva de Eretmochelys imbricata (testudines, cheloniidae) no litoral sul do Rio Grande do Norte, Brasil

Female hawksbill turtles (Eretmochelys imbricata) nesting along the southeastcoastline of Rio Grande do Norte State, Brazil (6º13'40"S, 35º03'05"W) were captured and weighed during the four months from January to April 2007, in the course of the annual egglaying season, which extended from 06 rd November 2006 to 30 rd May 2007. In all, 99 weight measurements were performed. On first contact the females exhibited an average post-oviposition weight of 79.1 kg (range 56.2-98.9 kg, SD = 10.9 kg, n = 44 females). Those individuals which were subsequently recaptured showed a mean weight loss of 1.7 kg (range 0.7-4.5 kg, SD = 1.0 kg, n = 39 sets of measurements on 20 females) in the interval between two consecutive post-ovipositions, separated by a maximum time interval of 17 days. In the cases where the female aborted the nesting process, the pre-oviposition weight was measured. The clutch weight, that is to say, the weight loss between consecutive pre-oviposition and post-oviposition measurements (separated by a maximum time interval of 3 days), was found to be 5.2 kg (range 4.3-6.0 kg, SD = 0.9 kg, n = 6 sets of measurements). This value is significantly higher (t-test, p<0.001) than the loss between two consecutive post-oviposition measurements with the same female. The mean recovery in body weight, that is to say, the average gain in weight between successive post-oviposition and pre-oviposition captures of the same individual (separated by a time interval of 12 to 17 days), was found to be 3.0 kg (range 1.9-4.3 kg, SD = 1.0 kg, n = 4 sets of measurements) Although the small sample size makes it unwise to generalise, the recovery in body weight was found to be always significantly lower (t-test, p<0.005) than the clutch weight. This fact is in agreement with the observed weight loss tendency throughout the breeding season for this species. Considering the clutch weight and the internidal recovery in body weight we found that the total weight loss of the adult hawksbill females after three to five nesting events varied from 10.4% (range 8.7-11.9%, SD = 1.6%, n = 3) to 14.1% (range 11.8-15.4%, SD = 1.3%, n = 6) in relation to their initial pre-oviposition weight. If there were no body weight recovery during the internesting interval we estimate that a female that nests three to five times in the course of the season would lose from 19% to 31% of its initial weight. We emphasise that our clutch weight estimate was performed by weighing the females and not by multiplying the number of eggs in the nest by their average unit weight. In this way, our measurements take into account the loss of liquid during the oviposition. Despite the unequivocal evidence of body weight recovery during the internidal interval, it is not clear if the cause of this process is rehydration or feeding

Effect of poultry viscera meal inclusion in broiler diets in different rearing periods on performance, carcass and parts yields

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estimates of genetic parameters for visual scores and their correlation with production and reproductive traits in Brahman cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Excesso de peso em região do nordeste brasileiro: contraste entre escolares de rede pública e privada de ensino

The prevalence of obesity has been increased in the last three decades. It is already considered as epidemic by the World Health Organization and reaches around 300 million people worldwide. The weight gain in all ages is related to a sedentary way of life and hyper caloric food ingestion at the modern society. Obesity is a chronic disease and leads to high blood pressure, diabetes, cardiovascular diseases and cancer. The aim of this study was to evaluate the prevalence of weight excess among student in Natal schools and to analyze its association with age, gender, school category and geographic localization in city zones. This was a transversal study which enrolled 1927 children. 1084 of these were between 6 and 8 years-old (group 1) and 843 were 9 to 10 years-old (group 2). 895 of the total children studied in private schools and 1032 studied in public schools. 33,6% of the students had body mass index equal or above the 85th percentile and were considered as having weight excess. There was no statistical difference in this prevalence considering neither gender nor age. The weight excess prevalence in private schools was 54,5% and in public ones was 15,6% (p<0,01; OR=6,49). Weight excess was also more prevalent in the south and east city zones (41,3%) which have better quality of life index than in the north and west zones (28,4%) (p<0,01). In conclusion, the weight excess prevalence among students is found to be high in Natal and programs of intervention and prevention of obesity are necessary. The higher prevalence in private schools as in the wealthier city zones reflects the link between obesity and high socioeconomic level found in countries in developing. This was an interdisciplinary work with participation of epidemiology, child nutrition and pediatric endocrinology following the recommendations and principles of the Post graduation Program in Health Sciences of the Federal University of Rio Grande do Norte

Síndrome metabólica e risco cardiovascular na pós- menopausa: avaliação por diferentes critérios diagnósticos e influência de fatores sócio-econômicos

The metabolic syndrome (MetS) involves a group of risk factors and is associated with a significantly higher risk of developing cardiovascular diseases (CVD) and type 2 diabetes. Recent studies have shown the importance of preventing CVD through early diagnosis and treatment of patients with MetS. The objective of our study was to determine the prevalence of MetS by different diagnostic criteria in postmenopausal women and analyze the influence of socioeconomic factors on cardiovascular risk in this sample of the population. A cross-sectional study involving 127 postmenopausal women (45 to 64 years) from Natal and Mossoró, Brazil. The study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte. The experimental protocol consisted of applying structured interview, clinical examination and implementation of dosages blood. The diagnosis of MetS was based on NCEP-ATP III (National Cholesterol Education Program-Adult Treatment Panel III) and IDF (International Diabetes Federation) criteria. The research was accomplished with the participation of an interdisciplinary team in their several phases. The result of the sample studied had mean age of 53.9 ± 4.6 years and per capita income of 54.5 dollars. The prevalence of MetS, according to NCEP-ATP III and IDF criteria, was 52.8% and 61.4$, respectively. The agreement rate between NCEP-ATP III and IDF criteria was 81.9%, with a kappa value of 0.63 (CI 95%, 0.49-0.76), indicating good agreement between the two definitions. The most prevalent cardiovascular risk factor was HDL < 50 mg/dl, observed in 96.1% of the women analyzed, followed by increased waist circumference (≥ 80 cm) in 78.0%, elevated blood pressure in 51.2%, triglycerides ≥ 150 mg/dl in 40.9% and glycemia ≥ 100 mg/dl in 37.0% of the women. The occurrence of MetS was significantly associated with schooling and body mass index (BMI). High blood pressure was significantly associated with low family income, low schooling and weight gain. There was no significant association between the intensity of climacteric symptomatology and the occurrence of MetS. The conclusions of the research were that MetS and its individual components show a high prevalence in postmenopausal Brazilian women, and significant associations with weight gain and low socioeconomic indicators. The data point to the need for an interdisciplinary approach at the basic health care level, directed toward the early identification of risk factors and the promotion of cardiovascular health of climacteric women.

Length-weight relationship and condition factor of the mangrove crab Ucides cordatus (Linnaeus, 1763) (Crustacea, Brachyura, Ucididae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Risco de doença cardiovascular em mulheres com história de distúrbio hipertensivo da gravidez

OBJECTIVE: Preeclampsia is a disease that can lead to a high maternal and infant morbidity. Worldwide, the incidence of this disease is highly variable and there is no data on this disorder in the Brazilian population. This study aimed at determining incidence and risk factors in the hypertensive disorders during pregnancy in a neighborhood of Natal, in addition to observing the evolution of these disorders one year and five years after delivery. METHODS: Prospective cohort study to assess the outcome of pregnancies of 242 women who became pregnant between 2004-2007 in the neighborhood of Bom Pastor in the city of Natal, state of RN, Brazil. Five years after delivery, there was an active search of thirty-nine (39) women who became pregnant and had a hypertensive disorder during pregnancy and/or pré-eclâmpsia, out of the total of 242 participants in the initial study. We administered a structured questionnaire to obtain basic information about the current clinical situation of patients and occurrences of subsequent pregnancy and presence of hypertensive disorders during pregnancy. We also searched for information on the use of hypotensive drugs and contraceptives. The following characteristics were checked and recorded: a) current weight, b) blood pressure c) body mass index - BMI, and we collected biological samples (blood and urine) for measurement of biochemical parameters and evaluation of microalbuminúria. Finally, we monitored the ambulatory blood pressure (ABP), which uses the method of automatic measurement of heart rate, systolic and diastolic blood pressure and an average of the two for the period of 24 hours. RESULTS: Out of 218 women who completed the study, the incidence of hypertensive disorders was of 16.9% (37 out of 218), while the incidence of preeclampsia was 13.8% (30 of 218). Women with preeclampsia had a BMI (body mass index) averaged of 25.3 (± 4.8) while this ratio in normotensive women was of 23.5 (± 3.7), p = 0.02. The risk of preeclampsia rises with age (OR 1084 p = 0.0034) and with a family history of hypertension (OR 2.6 p = 0.01). The follow-up one year after delivery revealed that 50% of women with hypertensive disorders in pregnancy remained hypertensive. High BMI was also observed after 5 years of delivery. CONCLUSIONS: an elevated BMI, age above 35 years and excessive weight gain during pregnancy were associated with hypertension in the long term in patients with prior preeclampsia. History of preeclampsia increases the risk of chronic hypertension

Performance and ruminal morphologic characteristics of Saanen kids fed ground, pelleted or extruded total ration

The aim of the present study was to determine feed intake and average weight gain and to evaluate the ruminal morphologic characteristics of Saanen kids slaughtered at 30, 45 and 60 days of age, according to a completely randomized design. Thirty-six non-castrated male Saanen kids were fed ground total ration, pelleted total ration, or extruded total ration. Feed intake and refusals were controlled daily and the animals were weighed at birth and then once a week. Newborn kids received a milk replacer and were weaned at 45 days. Immediately after slaughter, the animals were eviscerated, the entire digestive apparatus was removed from the carcass. The reticulo-rumen was separated, emptied, washed and weighed. Samples were collected from the dorsal sac, pillar area and ventral sac of the rumen, fixed for about 24h in Bouin's solution, dehydrated, embedded in Histosec and cut into 5 mu m sections. Results showed that dry matter intake (DMI) at weaning and post-weaning and weight gain were higher (P < 0.05) in animals that received the pelleted total ration. The weight of the reticulo-rumen accompanied body development and was heavier in these animals. Histologically, after weaning ruminal papillae were more developed in animals that received pelleted total ration. Length of papillae increased with increase of age. The ratio of papillary height to papillary width increased with age in the ventral sac and until weaning (P > 0.05). We conclude that the pelleting process of the total ration favored increased intake, with a 46.7% increase in weight gain and increase in rumen weight and papillae length, suggesting that best results are obtained with this processing. In general, no difference was observed between the results obtained with extruded and ground total ration, although animals fed extruded total ration showed an increase in rumen weight and papillae width. (c) 2004 Elsevier B.V All rights reserved.