Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model- independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns

Different circulating ghrelin responses to isoglucidic snack food in healthy individuals

The last decade has seen much debate on ghrelin as a potential target for treating obesity. Despite a close connection between snack food intake and obesity, snacking is controversially reviewed as a good habit in a healthy nutritional regimen. The aim of the study was to evaluate whether a different nutrient composition influences postprandial ghrelin levels and glucose increments induced by 6 isoglucidic snack food. 20 healthy individuals (10 M/10 F; BMI 23.1\ub10.5; age 33\ub10.67 years, mean and SE) from H San Raffaele Scientific Institute and Milan University were enrolled. The subjects underwent OGTT (50 g) and 6 isoglucidic test-meal loads to assess the ghrelin circulating levels and the area under glycemic curves induced by 6 commercial snacks. 3 h after hazelnut chocolate intake, ghrelin was significantly lower than with wafer chocolate intake (p<0.002). As a response to all snacks, the glycemic curves were not different even though hazelnut chocolate showed the lowest glycemic curve. Moreover, snack fat content was found to be inversely correlated to 3-h plasma ghrelin levels (p<0.0001; R2=0.77) and positively associated with satiety scores (p<0.02; R2=0.28). Also energy load was inversely correlated to 3-h plasma ghrelin (p<0.0001; R 2=0.73). Our results indicate that snack food administered in equivalent glucidic loads elicits postprandial ghrelin suppression and satiety ratings in different ways. Further studies are needed to elucidate the role of ghrelin as hunger-hormone in the regulation of energy balance

Desempenho acadêmico de doutores egressos do Programa de Pós-Graduação em Medicina Ciências Médicas da Faculdade de Medicina da UFRGS

Introdução: embora, no Brasil, muito tenha sido feito para estimular a criação e manutenção de programas de pós-graduação ainda há carência de meios para avaliar e para mensurar a evolução profissional dos egressos. O objetivo é compreender a trajetória dos Doutores formados pelo Programa de Pós-Graduação em Medicina Ciências Médicas (PPGCM), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS) e propor um índice de desempenho acadêmico e de inserção profissional. Métodos: foi realizado um estudo transversal. Foram coletados dados dos Currículos Lattes dos egressos de doutorado do Programa de Pós-Graduação em Medicina: Ciências Médicas (PPGCM), no período de 1987 a 2014. Foram extraídos apenas os dados pertinentes a sua origem, curso de graduação e de mestrado, produção intelectual, inserção acadêmica e a posição profissional. Resultados: foram analisados 324 doutores egressos, 221 eram graduados em Medicina. Foram utilizadas as variáveis: graduação em medicina, vínculo laboral em universidade pública, exerce atividade como orientador em nível de doutorado, exerce atividade como orientador em nível de mestrado, bolsista de produtividade em pesquisa do CNPq e possui registro do índice H no currículo Lattes. O coeficiente de determinação (R2) demonstrou que as variáveis incluídas no modelo explicam 99% do modelo hierárquico. Conclusão: os resultados demonstram que os egressos têm contribuído para a construção de conhecimento qualificado disseminado em jornais de circulação internacional, formação de recursos humanos, interagir e criar parcerias em seu ambiente de trabalho, gerenciar e repassar o conhecimento, bem como para fomentar o conhecimento na área das ciências médicas com relevância regional, nacional e internacional

Effects of restraint stress on the daily rhythm of hydrolysis of adenine nucleotides in rat serum

<p>Abstract</p> <p>Background</p> <p>Adenosine 5-triphosphate (ATP) and its breakdown products ADP and adenosine can act as extracellular messengers in a range of biological processes. Extracellular adenine nucleotides are metabolized by a number of enzymes including NTPDases and 5'-nucleotidase, which are considered to be the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATPase and ADPase activities in rat serum exhibit a 24-h temporal pattern, with higher enzyme activity during the dark (activity) phase. It was found that stress can cause disruptions in biological circadian rhythms and in the cardiovascular system. Therefore, the aim of the present study was to examine the influence of acute stress exposure upon temporal patterns of NTPDase and 5-nucleotidase enzyme activities in rat blood serum.</p> <p>Methods</p> <p>Adult male Wistar rats were divided into 4 groups: ZT0, ZT6, ZT12 and ZT18. Each group was subdivided in 4 groups: control, immediately, 6 h and 24 h after one hour of restraint stress. ATP, ADP and AMP hydrolysis were assayed in the serum.</p> <p>Results</p> <p>All stressed groups showed significant decreases in all enzyme activities at ZT 12 and ZT 18 when compared with control.</p> <p>Conclusion</p> <p>Acute stress provokes a decrease in nucleotidase activities dependent on the time that this stress occurs and this effect appears to persist for at least 24 hours. Stress can change levels of nucleotides, related to increased frequency of cardiovascular events during the activity phase. Altered levels of nucleotides in serum may be involved in cardiovascular events more frequent during the activity phase in mammals, and with their etiology linked to stress.</p

Circadian rhythm of activity levels: influence of chronotype.

Aim: The aim of this study is to investigate, by an actigraph monitoring, the differences in the circadian rhythm of activity level in relation to the chronotype for the sake of studying its influence on physical performance. Morning-type (M-type), Evening-type (E-types) and Neither-type (N-type) are the classified chronotypes; several studies showed the differences between M-types and E-types in the circadian rhythm of different physiological variables: M-types use to wake up and go to bed early and to have their best performances in the first part of the day, otherwise E-types go to bed and wake up late and they have the peak performances in the evening (Vitale et al., 2013). Method: The morningness\u2013eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To evaluate the circadian rhythmicity of activity levels we used the single cosinor method (Halberg et al., 1977) and we define three parameters characteristic of each statistically significant rhythm: M, MESOR (Midline Estimating Statistic Of Rhythm); A, Amplitude; \u3d5, acrophase. The population circadian characteristics were determined and then compared using the Hotelling test. Results: Rhythmometric analysis, with the single cosinor method, on the activity data collected by the actigraph revealed a statistically significant circadian rhythm (p<0.001) for all the 50 subjects. The population mean cosinors were calculated grouping the different chronotypes: M-types, E-types and N-types (p<0.001). No statistical differences about MESOR were showed for all group combinations (p>0.05) but a significant difference (p<0.05) was observed if considering the Amplitude-Acrophase test for all groups combinations, in particular M-types had an early acrophase of the circadian rhythm of the activity levels, at 14.37, while E-types showed an acrophase with more than 2 hours late, at 17.04 (p<0.001); the group of Ntypes showed an intermediate acrophase, at 15.45, between morning-types and evening-types. Conclusion: We can assume that there is a clear difference between \u201clarks\u201d and \u201cowls\u201d and this results are in line with other studies that showed the biological differences among chronotypes. We can conclude that M-types are more active in the early afternoon and that E-types have the peak of their activity in the late afternoon. Further studies are needed to better understand if and how the chronotype influence a physical performance. References 1. Halberg F., Carandente F., Cornelissen G., Katinas G.S. (1977). Glossary of chronobiology. Chronobiologia 4 (Suppl. 1):1-189. 2. Vitale J.A., Calogiuri G., Weydahl A. (2013). Percept. Mot. Skills. 116(3):1020-1028

Aerobic 3-month physical activity program in breast cancer survivors: effects on sleep behavior, anthropometric indices of adiposity and fasting glucose metabolism

Background: Evidences exist that sleep disorders are associated with an increased risk of cancer, including breast cancer (BC) (Verkasalo et al., 2005). Also adiposity and hypersinsulinemia have been acknowledged as factors involved in cancer mortality including BC (Pisani, 2008). Physical activity (PA) has the potential to counterbalance all of these risk factors. In fact, PA has been shown to produces beneficial effects on sleep quality and BC prognosis, as well as on adiposity and glucose metabolism (Mann et al., 2014). We thus designed a randomized controlled trial to test the effect of an aerobic PA program on sleep behavior, anthropometric indices of adiposity and fasting glucose metabolism in BC women included in a dietary intervention trial for prevention of BC recurrences. Subjects and Methods: 42 BC women, aged 35-70 years, wererandomized into an intervention (IG=19) and control group (CG=23). The IG had to participate in a 3-month active PA program that included two sessions of one-hour brisk walking per week. At baseline and after 3-month, all women were requested to undergo an anthropometric visit, to collect a blood sample for detemination of fasting insulin and glucose levels, to wear the Actigraph Actiwatch for one week for sleep parameters evaluation (Actual Sleep Time (AST), Actual Wake Time (AWT), Sleep Efficiency (SE); Sleep Latency (SL); Mean Activity Score (MAS); Movement and Fragmentation Index (MFI) and Immobility time (IT)). Results: At the end of the 3-month PA program, CG showed an overall worsening of sleep behaviour. In fact, SE, IT and AST decreased (p&lt;0.01), while AWT, MAS and MFI increased (p&lt;0.01). In contrast, IG did not show any sign of sleep deterioration. As for the indices of adiposity, a significant reduction in waist circumference (p&lt;0.05) and % fat mass (p&lt;0.01) was observed in IG, but not in CG. Although fasting glucose and insulin levels did not show any significant change in either group, it was nevertheless encouraging that the two groups displayed an opposite trend as far as the changes in fasting insulin were concerned: fasting insulin showed a mean reduction (-0.9 \u3bcU//ml) in the IG group and a mean increment in the CG (+0.7 \u3bcU/ml). Conclusion: Our results suggest that a standardized PA program in BC survivors prevents sleep deterioration, reduces anthropometric indices of adiposity and may prove useful in preventing the development of hyperinsulinemic levels. REFERENCES 1. Mann et al. (2014). Diabetes Metab Res Rev. 30: 257-268 2. Pisani P. (2008). Arch Physiol Biochem 114: 63\u201370. 3. Verkasalo PK et al. (2005). Cancer Res 65(20): 9595\u2013600

Actigraphy-based activity levels and anthropometric measurements in breast cancer survivors: effects of aerobic physical activity

The research investments for the identification of modifiable factors associated with BC recurrences is increasing. Adiposity and other anthropometric indices have been acknowledged as factors involved in BC recurrences and mortality (1). Physical activity (PA) has the potential to counterbalance all of these risk factors (2). We designed a randomized controlled trial to test the effect of an aerobic PA program on anthropometric indices of adiposity and circadian rhythm activity level, evaluated by actigraphy, in BC women included in a dietary intervention trial for prevention of BC recurrences. 40 BC women, aged 35-70 years, were randomized into an intervention (IG=19) and a control group (CG=21). The IG participated in a 3-month active PA program that included two sessions of one-hour brisk walking per week. At baseline and after 3 months, both IG and CG were evaluated for the following parameters: height, weight, BMI, waist circumferences, % fat mass, % lean mass; energy expenditure and motion level (Total Energy Expenditure-TEE, number of steps, PA level, Metabolic Equivalents-METs) using a SenseWear Pro 3 Armband; and activity level circadian rhythm using the Actigraph Actiwatch. At the end of the 3-month PA program, IG showed a significant reduction in fat mass % while CG improved weight and BMI. The population mean cosinor applied to IG and CG at PRE and POST revealed the presence of a significant circadian rhythm in two groups (

Spontaneous nocturnal growth hormone secretion in anorexia nervosa

In anorexia nervosa, serum GH levels are increased under basal conditions and respond abnormally to provocative stimuli. We report here, for the first time, an analysis of pulsatile GH secretion in these patients performed by Cluster algorithm. Seven anorectic and six normal weight, healthy women underwent serial blood sampling at 20-min intervals form 2030-0830 h for GH estimation. The total area under the curve (AUC; micrograms per L/min) was elevated 4-fold in anorectic patients compared to controls (4743.0 +/- 1520.09 vs. 1148.6 +/- 519.27; P < 0.01), largely due to an increase in the non-pulsatile fraction (3212.5 +/- 990.45 vs. 378.7 +/- 123.27; P < 0.01). Accordingly, the valley mean value was higher in anorectic than in control subjects (5.9 +/- 2.25 vs. 1.0 +/- 1.30 micrograms/L; P < 0.01). Furthermore, pulsatile AUC was also greater in anorectic patients (1530.4 +/- 654.72 vs. 769.8 +/- 404.02; P < 0.01) due to a significant increase in GH peak frequency (5.0 +/- 0.81 vs. 3.0 +/- 0.89; P < 0.01). No correlations were observed in these patients between body mass index and any of the parameters of spontaneous GH release, whereas a positive correlation was found between insulin-like growth factor I levels and pulsatile AUC (r2 = 0.583; P < 0.05), peak height (r2 = 0.743; P = 0.01), peak increment (r2 = 0.801; P < 0.01), and GH valley mean (r2 = 0.576; P < 0.05). In conclusion, it appears that the enhanced GH secretion in anorexia nervosa is the result of an increased frequency of secretory pulses superimposed on enhanced tonic GH secretion. Although this latter is consistent with a reduction of hypothalamic SRIH tone, the former may be accounted for by an increased number of GHRH discharges. Considering that in normal weight and obese subjects parameters of GH release are negatively correlated with adiposity indexes, the lack of such a negative correlation in our patients suggests that the enhancement of spontaneous GH release in anorectic patients is not merely the consequence of malnutrition-dependent impairment of insulin-like growth factor I production, but reflects a more complex hypothalamic dysregulation of GH release

Anthropometric indices of adiposity and fasting glucose metabolism in breast cancer survivors: effects of aerobic physical activity

Adiposity and hypersinsulinemia are factors involved in cancer mortality including BC (1). Physical activity (PA) has the potential to counterbalance these risk factors. In fact, PA has been shown to produce beneficial effects on adiposity and glucose metabolism (2). We thus designed a randomized controlled trial to test the effect of an aerobic PA program on anthropometric indices of adiposity and fasting glucose metabolism in BC women included in a dietary intervention trial for prevention of BC recurrences. 42 BC women, aged 35-70 years, were randomized into an intervention (IG=19) and control group (CG=23). The IG had to participate in a 3-month active PA program that included two sessions of one-hour brisk walking per week. At baseline and after 3-month, all women were requested to undergo an anthropometric visit and to collect a blood sample for determination of fasting insulin and glucose levels. At the end of the 3-month PA a significant reduction in waist circumference (p&lt;0.05) and percentage fat mass (p&lt;0.01) were observed in IG, but not in CG. In addition, only IG increased significantly their Metabolic Equivalent of Task (METs) (p&lt;0.05). Although fasting glucose and insulin levels don\u2019t show any significant change in either group, it is nevertheless encouraging that the two groups displayed an opposite trend as far as the changes in fasting insulin were concerned: fasting insulin shows a mean reduction (-0.9 \uf06dU//ml) in the IG group and a mean increment in the CG (+0.7 \uf06dU/ml). The results suggest that a standardized PA program in BC survivors reduces anthropometric indices of adiposity and may prove useful in preventing the development of hyperinsulinemic levels. References 1. Mann et al. (2014) Changes in insulin sensitivity in response to different modalities of exercise: a review of the evidence. Diabetes Metab Res Rev. 30(4): 257-268. 2. Pisani (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114(1): 63\u201370