Randomized clinical trial to evaluate the effect on postprandial glycemia of Nutren Control®, a glycemia-targeted specialized supplement, compared to standardized breakfast in patients with type-2 diabetes: the CONTROL DIABETES study / Ensayo clínico aleatorizado para evaluar el efecto sobre la glucemia posprandial de Nutren Control®, un suplemento especializado dirigido a la glucemia, en comparación con el desayuno estandarizado en pacientes con diabetes de tipo 2: el estudio CONTROL DIABETES

Objective: to evaluate the effects of a new glycemia targeted specialized supplement (GTSS) compared to a standard breakfast on postprandial blood glucose (PPG). Methods: patients with type 2 diabetes (T2D) and suboptimal control (A1C between 6.5 and 8.5 %) in monotherapy with metformin were included to this prospective, randomized, crossover trial. The standardized breakfast was isoenergetic compared to the GTSS, differing on macronutrients distribution. Both interventions were used once a day in the morning, each replacing breakfast for 7 consecutive days (14 days of observation). Intermittent scanning continuous glucose monitoring system (isCGM) determined the difference between the interventions regarding the incremental area under the curve (iAUC) of the PPG (3 hours after intervention), as a primary endpoint; secondary endpoints were the difference between the interventions regarding the glycemic peak, postprandial glucose excursion (PPGE), mean blood glucose (MBG) and time in range (TIR). Results: thirty-one T2D patients with ages between 39 and 69 years-old were enrolled. GTSS group had significantly lower iAUC of the PPG compared to standardized breakfast (33.3 [15.0 to 54.0] vs 46.8 [27.3 to 75.1] mg/dL), while also presenting a significantly lower PPG excursion (26.4 ± 17.2 vs 44.8 ± 24.4 mg/dL). There was no difference between the intervention periods regarding MBG, TIR and hypoglycemic events. Conclusion: The new GTSS, as a meal replacement in the breakfast, produced a 25 % reduction in the iAUC of the PPG, as accessed by isCGM, in comparison with an isocaloric-standardized meal. (AU)

Objetivo: evaluar los efectos de un suplemento especializado en el control de la glucosa (GTSS) frente a un desayuno estándar sobre la glucemia posprandial (PPG). Metodología: es un estudio cruzado, prospectivo, aleatorizado en el que se incluyeron a pacientes con diabetes tipo 2 (T2D) con control subóptimo de la glucemia (HbA1c entre 6,5 y 8,5 %) utilizando monoterapia con metformina. El desayuno estandarizado fue isocalórico en comparación con el GTSS y solamente la distribución calórica fue diferente. Ambas intervenciones se utilizaron una vez al día por la mañana, reemplazando cada una el desayuno durante 7 días consecutivos (14 días de observación). Se utilizó el sistema de monitoreo continuo de glucosa (isCGM) para determinar las diferencias entre las intervenciones con respecto al área bajo la curva (iAUC) de glucosa postprandial (PPG) (3 horas después de la intervención) como variable principal o primaria; las variables secundarias fueron la diferencia entre las intervenciones con respecto al pico glicémico, la excursión de glucosa posprandial (PPGE), la glucosa media en sangre (MBG) y el rango de tiempo (TIR). Resultado: se incluyeron treinta y un pacientes con T2D con edades entre 39 y 69 años. El grupo del GTSS tuvo un área bajo la curva (iAUC) significativamente más baja de la PPG en comparación con el grupo del desayuno estandarizado (33,3 [15,0 a 54,0] frente a 46,8 [27,3 a 75,1] mg/dL), mientras que también presentó una PPG significativamente más baja (26,4 + 17,2 vs. 44,8 + 24,4 mg/dL). No hubo diferencia entre los períodos de intervención con respecto a la MBG, el TIR y eventos hipoglucémicos. Conclusión: el nuevo GTSS, como sustituto del desayuno, produjo una reducción de la iAUC de la PPG del 25 %, según el isCGM, en comparación con un desayuno isocalórico normalizado. (AU)

Randomized clinical trial to evaluate the effect on postprandial glycemia of Nutren Control®, a glycemia-targeted specialized supplement, compared to standardized breakfast in patients with type-2 diabetes: the CONTROL DIABETES study.

Introduction: Objective: to evaluate the effects of a new glycemia targeted specialized supplement (GTSS) compared to a standard breakfast on postprandial blood glucose (PPG). Methods: patients with type 2 diabetes (T2D) and suboptimal control (A1C between 6.5 and 8.5 %) in monotherapy with metformin were included to this prospective, randomized, crossover trial. The standardized breakfast was isoenergetic compared to the GTSS, differing on macronutrients distribution. Both interventions were used once a day in the morning, each replacing breakfast for 7 consecutive days (14 days of observation). Intermittent scanning continuous glucose monitoring system (isCGM) determined the difference between the interventions regarding the incremental area under the curve (iAUC) of the PPG (3 hours after intervention), as a primary endpoint; secondary endpoints were the difference between the interventions regarding the glycemic peak, postprandial glucose excursion (PPGE), mean blood glucose (MBG) and time in range (TIR). Results: thirty-one T2D patients with ages between 39 and 69 years-old were enrolled. GTSS group had significantly lower iAUC of the PPG compared to standardized breakfast (33.3 [15.0 to 54.0] vs 46.8 [27.3 to 75.1] mg/dL), while also presenting a significantly lower PPG excursion (26.4 ± 17.2 vs 44.8 ± 24.4 mg/dL). There was no difference between the intervention periods regarding MBG, TIR and hypoglycemic events. Conclusion: The new GTSS, as a meal replacement in the breakfast, produced a 25 % reduction in the iAUC of the PPG, as accessed by isCGM, in comparison with an isocaloric-standardized meal.

Introducción: Objetivo: evaluar los efectos de un suplemento especializado en el control de la glucosa (GTSS) frente a un desayuno estándar sobre la glucemia posprandial (PPG). Metodología: es un estudio cruzado, prospectivo, aleatorizado en el que se incluyeron a pacientes con diabetes tipo 2 (T2D) con control subóptimo de la glucemia (HbA1c entre 6,5 y 8,5 %) utilizando monoterapia con metformina. El desayuno estandarizado fue isocalórico en comparación con el GTSS y solamente la distribución calórica fue diferente. Ambas intervenciones se utilizaron una vez al día por la mañana, reemplazando cada una el desayuno durante 7 días consecutivos (14 días de observación). Se utilizó el sistema de monitoreo continuo de glucosa (isCGM) para determinar las diferencias entre las intervenciones con respecto al área bajo la curva (iAUC) de glucosa postprandial (PPG) (3 horas después de la intervención) como variable principal o primaria; las variables secundarias fueron la diferencia entre las intervenciones con respecto al pico glicémico, la excursión de glucosa posprandial (PPGE), la glucosa media en sangre (MBG) y el rango de tiempo (TIR). Resultado: se incluyeron treinta y un pacientes con T2D con edades entre 39 y 69 años. El grupo del GTSS tuvo un área bajo la curva (iAUC) significativamente más baja de la PPG en comparación con el grupo del desayuno estandarizado (33,3 [15,0 a 54,0] frente a 46,8 [27,3 a 75,1] mg/dL), mientras que también presentó una PPG significativamente más baja (26,4 + 17,2 vs. 44,8 + 24,4 mg/dL). No hubo diferencia entre los períodos de intervención con respecto a la MBG, el TIR y eventos hipoglucémicos. Conclusión: el nuevo GTSS, como sustituto del desayuno, produjo una reducción de la iAUC de la PPG del 25 %, según el isCGM, en comparación con un desayuno isocalórico normalizado.

Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study.

BACKGROUND: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). METHODS: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned. RESULTS: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified. CONCLUSIONS: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).

Impact of regulatory assessment on clinical studies in Brazil / Impacto da avaliação regulatória em estudos clínicos no Brasil

SUMMARY Introduction: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. Objective: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. Method: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. Results: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. Conclusion: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country’s scientific development.

RESUMO Introdução: apesar da recente expansão de estudos clínicos alocados para o Brasil, a demora dos prazos regulatórios locais impacta diretamente em sua realização. Objetivo: este artigo analisa o processo de alocação de estudos clínicos para o Brasil em comparação a outros países, bem como o impacto financeiro dos estudos não realizados em decorrência da interrupção pela demora no processo regulatório. Método: foram comparados os processos de alocação de estudos em nove países com estágios semelhantes de desenvolvimento econômico e países da América Latina através dos siteshttp://data.worldbank.org/data-catalog/GDP-ranking-table, http://worldpopulationreview.com e clinicaltrials.gov, que engloba 185 países. Os 46 estudos patrocinados pela indústria farmacêutica tiveram o processo de avaliação regulatória analisado. Resultados: foram analisados 46 estudos patrocinados pela indústria submetidos no país entre junho de 2007 e junho de 2013; 18 (39%) foram descontinuados pelo atraso na obtenção das aprovações necessárias. Para os estudos aprovados, o recrutamento de pacientes começou, em média, aos 11 meses após os demais países. Estima-se que 530 pacientes brasileiros não tiveram a oportunidade de participar desses estudos. As perdas financeiras foram da ordem de 14,6 milhões de dólares para o país, incluindo custos com paciente, medicação, suprimentos e despesas administrativas. Conclusão: o Brasil tem um enorme potencial para a realização de estudos clínicos. Investigadores, associações de deficientes e pacientes portadores de doenças crônicas, patrocinadores e autoridades devem trabalhar juntos para desenvolver um processo de aprovação eficiente, previsível e antes de tudo transparente. O atual ambiente regulatório deve e pode ser melhorado e aperfeiçoado, caso contrário não resultará em benefícios tangíveis para o paciente, para a sociedade e a evolução médico-científica do país.

Impact of regulatory assessment on clinical studies in Brazil.

INTRODUCTION: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. OBJECTIVE: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. METHOD: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. RESULTS: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. CONCLUSION: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.

Association of back pain with hypovitaminosis D in postmenopausal women with low bone mass.

BACKGROUND: Back pain is a major public health problem due to its high frequency, to the resulting activity constraint, and the need for surgery in many cases. Back pain is more frequent in women than men, mainly in postmenopausal women. High prevalence of hypovitaminosis D has been detected in postmenopausal women, and it is associated with decreased bone mass, sarcopenia, vertebral fractures, and inflammation, which can be related to back pain. METHODS: The relation between back pain and hypovitaminosis D was evaluated in this study, as well the difference regarding the number of bedridden days, number of days away from work, and daily activities limitation between women with and without hypovitaminosis D. This study reviewed baseline data from an interventional phase III multicenter trial in low bone mass postmenopausal women. The study included demographic data, 25OHD determinations, Newitt/Cummings questionnaire on back pain, and vertebral fracture identified thought X-ray evaluation. RESULTS: The trial included 9354 participants, but only 9305 underwent all the evaluations. The age median was 67 (60 - 85 years old) and age at menopause was 49 (18 - 72 years). Hypovitaminosis D was found in 22.5% of the subjects, 15.3% of them had vertebral fractures, 67.5% with back pain, and 14.8% reduced their daily activities in the previous six months. Subjects with hypovitaminosis D, compared to those without hypovitaminosis D, reported more back pain (69.5 v 66.9%, p: 0.022), more cases of severe back pain (8.5% v 6.8%, p: 0,004), higher limitation in their daily activities (17.2 v 14.0%, p: 0.001), and more fractures (17.4 v 14.6%, p: 0,002); also, they had more trouble to perform daily activities addressed in the Newwit/Cummings questionnaire. CONCLUSION: Hypovitaminosis D was related to back pain, to its severity, and to difficulty in perform daily activities. TRIAL REGISTRATION: ClinicalTrial.gov: NCT00088010.

Body composition, metabolic syndrome and insulin resistance in type 1 diabetes mellitus.

OBJECTIVE: Our aim was to determine the relationship between body fat composition, metabolic syndrome (MS), and insulin resistance in type 1 diabetes (DM1). SUBJECTS AND METHODS: Forty-five DM1 women (36 ± 9 years; body mass index 24.6 ± 4.4 kg/m(2)) had body composition and insulin resistance determined by dual-energy X-ray absorptiometry and estimated glucose disposal ratio (eGDR), respectively. Twenty patients (45%) had MS according to World Health Organization (WHO) criteria. RESULTS: Women with DM1 and MS had increased central fat and lower eGDR than women without MS (41.9 ± 2.0 vs. 33.7 ± 1.8%; p = 0.004 and 4.99 ± 0.40 vs. 8.37 ± 0.39; p < 0.0001, respectively). Total body fat and peripheric fat were similar between the groups. Central fat negatively correlated with eGDR (r = -0.33; p = 0.03). CONCLUSION: Central fat deposition in young non-obese DM1 women was related to MS and insulin resistance. Thus, body fat composition analysis might be important to identify DM1 patients with increased metabolic risk.

Body composition, metabolic syndrome and insulin resistance in type 1 diabetes mellitus / Composição corporal, síndrome metabólica e resistência insulínica no diabetes melito tipo 1

OBJECTIVE: Our aim was to determine the relationship between body fat composition, metabolic syndrome (MS), and insulin resistance in type 1 diabetes (DM1). SUBJECTS AND METHODS: Forty-five DM1 women (36 ± 9 years; body mass index 24.6 ± 4.4 kg/m²) had body composition and insulin resistance determined by dual-energy X-ray absorptiometry and estimated glucose disposal ratio (eGDR), respectively. Twenty patients (45 percent) had MS according to World Health Organization (WHO) criteria. RESULTS: Women with DM1 and MS had increased central fat and lower eGDR than women without MS (41.9 ± 2.0 vs. 33.7 ± 1.8 percent; p = 0.004 and 4.99 ± 0.40 vs. 8.37 ± 0.39; p < 0.0001, respectively). Total body fat and peripheric fat were similar between the groups. Central fat negatively correlated with eGDR (r = -0.33; p = 0.03). CONCLUSION: Central fat deposition in young non-obese DM1 women was related to MS and insulin resistance. Thus, body fat composition analysis might be important to identify DM1 patients with increased metabolic risk.

OBJETIVO: Avaliar a relação entre composição corporal, síndrome metabólica (SM) e resistência insulínica (RI) no diabetes tipo 1 (DM1). SUJEITOS E MÉTODOS: Quarenta e cinco mulheres com DM1 (36 ± 9 anos; índice de massa corporal 24,6 ± 4,4 kg/m²) foram submetidas à análise de composição corporal e RI por meio de densitometria por dupla emissão de raios-X e taxa de disponibilização de glicose estimada (eGDR), respectivamente. Vinte mulheres (45 por cento) apresentavam SM, conforme critérios da Organização Mundial da Saúde (OMS). RESULTADOS: Mulheres com SM apresentaram maior gordura central e menor eGDR do que as sem SM (41,9 ± 2,0 vs. 33,7±1,8 por cento; p = 0,004 e 4,99 ± 0,40 vs. 8,37 ± 0,39; p < 0,0001). A gordura corporal total e a gordura periférica não diferiram entre os grupos. A gordura central foi inversamente correlacionada com eGDR (r = -0,33; p = 0,03). CONCLUSÃO: Deposição de gordura central em mulheres jovens não obesas com DM1 esteve associada com SM e RI. Avaliação da composição corporal pode ser importante na identificação de pacientes com risco metabólico elevado.

Increased epicardial adipose tissue in type 1 diabetes is associated with central obesity and metabolic syndrome.

AIMS: The present study evaluated the relationship between metabolic syndrome (MS), body fat composition and epicardial adipose tissue (EAT) in type 1 diabetes. Epicardial adipose tissue is a new independent marker of coronary artery disease (CAD). METHODS: forty-five type 1 diabetic women were evaluated (age 36 ± 9 years; body mass index 24.6 ± 4.4 kg/m(2)). Metabolic syndrome was defined by the World Health Organization criteria. Body fat composition and EAT were analyzed by dual-energy-X-ray absorptiometry and echocardiogram, respectively. RESULTS: twenty patients (45%) had MS. Patients with MS had greater android (central) fat deposition than patients without MS (41.9 ± 2.0% vs. 33.7 ± 1.8%, p=0.004). Total body fat and gynoid (peripheric) fat distribution were similar between the groups. Mean EAT was higher in patients with MS (6.15 ± 0.34 mm vs. 4.96 ± 0.25 mm; p=0.006) and EAT was positively correlated with android (central) fat distribution (r=0.44; p=0.002), however no correlation was found with gynoid (peripheric) fat distribution. CONCLUSIONS: there was a high incidence of MS in type 1 diabetes related to increased central adiposity, despite the absence of obesity. Metabolic syndrome and central obesity were associated with increased EAT. Thus, young non-obese type 1 diabetic women with central adiposity and/or MS may have increased EAT, what may predict CAD risk.

Concentração plasmática de 25 hidroxivitamina D em mulheres na pós-menopausa com baixa densidade mineral óssea / Concentration of 25-hydroxyvitamin D in postmenopausal women with low bone mineral density

OBJETIVOS: Determinar as concentrações plasmáticas médias de 25 hidroxivitamina D (25OHD) em mulheres na pós-menopausa com baixa densidade mineral óssea (DMO); encontrar o ponto de corte de elevação do paratormônio (PTH); avaliar a correlação entre 25OHD e DMO, parâmetros bioquímicos e presença de fraturas vertebrais. MÉTODOS: Estudo transversal, com dosagem de 25OHD e de PTH, e realização de DMO e radiografia de coluna. RESULTADOS: Houve elevada frequência de concentrações plasmáticas inadequadas de 25OHD (68,3 por cento) e 8 por cento de hiperparatireoidismo secundário. Não foram observadas diferenças significativas entre as concentrações plasmáticas de 25OHD e os parâmetros avaliados, exceto PTH, que apresentou associação inversa. O ponto de corte determinado foi de 61,5 nmol/L. CONCLUSÕES: A alta frequência de hipovitaminose D em idosas com baixa DMO sugere que a avaliação sistemática das concentrações plasmáticas de 25OHD deve ser realizada nessa população. Recomenda-se o uso de ponto de corte de 61,5 nmol/L até a realização de estudo epidemiológico que represente toda a cidade do Rio de Janeiro (RJ).

OBJECTIVES: This study was designed to determine mean serum concentrations of 25-hydroxyvitamin D (25OHD) in postmenopausal women with low bone mineral density (BMD), to find the cutoff of parathormone (PTH) elevation, and to evaluate the correlation 25OHD with BMD, biochemical parameters and vertebral fracture presence. METHODS: Transversal study, with collection of 25OHD and PTH, and determination of DMO and column radiograph. RESULTS: A high incidence of inadequate serum concentrations of 25OHD (68.3 percent) was found and 8 percent of secondary hyperparathyreoidism. No significant differences were found between 25OHD serum concentrations and the evaluated parameters, except for PTH, which showed a negative association. The established cutoff was 61.5 nmol/L. CONCLUSIONS: The elevated incidence of hipovitaminosis D in elderly women with low BMD suggests that a systematic evaluation of 25OHD serum concentrations must be done for this population.The use of 61.5 nmol/L as a cutoff is recommended until the realization of an epidemiologic study that represents all Rio de Janeiro city (RJ, Brazil).

[Concentration of 25-hydroxyvitamin D in postmenopausal women with low bone mineral density]. / Concentração plasmática de 25 hidroxivitamina D em mulheres na pós-menopausa com baixa densidade mineral óssea.

OBJECTIVES: This study was designed to determine mean serum concentrations of 25-hydroxyvitamin D (25OHD) in postmenopausal women with low bone mineral density (BMD), to find the cutoff of parathormone (PTH) elevation, and to evaluate the correlation 25OHD with BMD, biochemical parameters and vertebral fracture presence. METHODS: Transversal study, with collection of 25OHD and PTH, and determination of DMO and column radiograph. RESULTS: A high incidence of inadequate serum concentrations of 25OHD (68.3%) was found and 8% of secondary hyperparathyreoidism. No significant differences were found between 25OHD serum concentrations and the evaluated parameters, except for PTH, which showed a negative association. The established cutoff was 61.5 nmol/L. CONCLUSIONS: The elevated incidence of hipovitaminosis D in elderly women with low BMD suggests that a systematic evaluation of 25OHD serum concentrations must be done for this population.The use of 61.5 nmol/L as a cutoff is recommended until the realization of an epidemiologic study that represents all Rio de Janeiro city (RJ, Brazil).

[Profile of clinical research subjects in an independent outpatient center]. / Perfil de sujeitos de pesquisa clínica em um centro ambulatorial independente.

This paper assesses the quality of assistance in a clinical trial outpatient center as well as the patients understanding of the informed consent (IC); determine the reasons why they participate and detail socio-economic levels. A cross-sectional study was adopted in a clinical trial outpatient center using a self-explanatory questionnaire. All 100 respondents considered the assistance at the center excellent (86%) or good (9%). Almost all of them were well informed about the content of the IC. Their knowledge about the right to "confidentiality", present in all ICs, was 6 times higher than their knowledge about their right to "access the results", generally not included in the IC. The main reasons for participating were "to know more about ones health" (59%) and to "to benefit other people in the future" (47%). The participants income varied from 3 to 5 minimum wages (48%) and most (66%) concluded at least the 4th grade of basic education in Brazil. The subjects showed the economical characteristics of the average population of Rio de Janeiro. Their level of education allowed them to sign and to understand what they were signing. They were aware of the existence of the IC and its content. The main reason for participating was for one s own benefit and for the benefit of others.

Perfil de sujeitos de pesquisa clínica em um centro ambulatorial independente / Profile of clinical research subjects in an independent outpatient center

Este artigo tem como objetivos avaliar a qualidade de atendimento de um centro de pesquisa clínica e o entendimento do termo de consentimento informado (TCLE); determinar os motivos da participação e detalhar níveis socioeconômicos. Foi feito um estudo transversal em centro de pesquisa ambulatorial, através de questionário auto-explicativo. Dos cem questionários avaliados, todos os sujeitos de pesquisa consideraram o centro como ótimo (86 por cento) ou bom (9 por cento). A quase totalidade foi bem informada do conteúdo do TCLE e o conhecimento do direito "confidencialidade", comum a todos os TCLEs, foi seis vezes maior que " acesso aos dados", que não faz parte. Os principais motivos para participarem foram para "saber mais sobre a sua saúde" (59 por cento) e para "beneficiar outras pessoas no futuro" (47 por cento). A principal faixa de renda salarial dos participantes foi entre dois e cinco salários mínimos (48 por cento) e a maioria (66 por cento) concluiu pelo menos até a 4º série do ensino fundamental. A população possui o mesmo perfil econômico do Rio de Janeiro, nível de escolaridade suficiente para assinar e compreender o que está assinando, conhecendo não só a existência do TCLE, mas demonstrando conhecer seu conteúdo. O motivo principal para participação é para autobenefício e por atitude altruísta.

This paper assesses the quality of assistance in a clinical trial outpatient center as well as the patients´understanding of the informed consent (IC); determine the reasons why they participate and detail socio-economic levels. A cross-sectional study was adopted in a clinical trial outpatient center using a self-explanatory questionnaire. All 100 respondents considered the assistance at the center excellent (86 percent) or good (9 percent). Almost all of them were well informed about the content of the IC. Their knowledge about the right to "confidentiality", present in all ICs, was 6 times higher than their knowledge about their right to "access the results", generally not included in the IC. The main reasons for participating were "to know more about ones health" (59 percent) and to "to benefit other people in the future" (47 percent). The participants´ income varied from 3 to 5 minimum wages (48 percent) and most (66 percent) concluded at least the 4th grade of basic education in Brazil. The subjects showed the economical characteristics of the average population of Rio de Janeiro. Their level of education allowed them to sign and to understand what they were signing. They were aware of the existence of the IC and its content. The main reason for participating was for one´s own benefit and for the benefit of others.

Glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis / Osteoporose induzida por glicocorticóide

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.

A osteoporose induzida por glicocorticóides é a causa mais freqüente de osteoporose secundária. Os glicocorticóides causam uma perda óssea rápida nos primeiros meses de uso da medicação; entretanto, o seu efeito mais importante é uma supressão significativa da formação óssea. A administração oral de glicocorticóides está associada a um aumento no risco de fraturas na coluna e no quadril. O risco é dose dependente; entretanto, mesmo doses baixas de glicocorticóides podem aumentar o risco de fraturas. Os pacientes em uso de glicocorticóides perdem mais osso trabecular que osso cortical; em conseqüência, as fraturas são mais freqüentes na coluna que no quadril. O uso concomitante de cálcio e vitamina D ou formas ativas da vitamina D previne a perda óssea, e as drogas anti-reabsortivas são efetivas na prevenção e tratamento da perda óssea e diminuem o risco de fraturas. Apesar de os efeitos deletérios dos glicocorticóides sobre o osso serem bastante conhecidos, poucos pacientes são orientados ou recebem tratamento preventivo associado à terapia com glicocorticóides.

Diagnóstico e tratamento da osteoporose: avaliação da freqüência em centro especializado no Rio de Janeiro / Diagnosis and treatment of osteoporosis: frequency in a Rio de Janeiro Osteoporosis Center

A osteoporose é doença freqüente, caracterizada por uma diminuição da densidade mineral óssea e aumento no risco de fraturas. É atualmente problema de saúde pública em todo mundo com custos cada vez maiores. O objetivo deste estudo foi avaliar a freqüencia de osteopenia e osteoporose em pacientes examinados em um Centro de Diagnóstico de Osteoporose no Rio de Janeiro e o uso de medicamentos que atuam sobre o esqueleto nestes pacientes. Foram analisados os resultados de 2.270 exames de densitometria óssea em um período de 90 dias. Os autores avaliaram a distribuição quanto ao sexo, faixa etária, diagnóstico, sítios do esqueleto analisados e tratamento instituído. Na análise dos dados foi aplicado o teste do qui quadrado e na comparação das proporções e relação entre os tratamentos e o diagnóstico foi utilizado o teste Z da curva normal. Observamos que a idade média dos pacientes foi de 59ñ10,9 anos, 2.237 eram do sexo feminino e 33 do sexo masculino. Os resultados mostraram que 46,9 por cento apresentavam osteopenia e 19,4 por cento apresentavam osteoporose. Entre os pacientes com osteopenia apenas 55,1 por cento estavam usando alguma medicação e entre aqueles com osteoporose apenas 59,6 por cento estavam sendo tratados (7,3 por cento usavam o medicamento da classe dos bisfosfonatos, o alendronato e 4,2 por cento usavam o raloxifeno da classe dos SERMs). Os autores concluem que apesar da presença elevada de casos de osteopenia e ou osteoporose detectados através do exame de sensitometria óssea, um grande número de pacientes não está sendo efetivamente tratado

Consenso brasileiro de osteoporose 2002 / Brazilian consensus on osteoporosis 2002

Objetivo: estabelecer diretrizes para o diagnóstico precoce, prevenção e tratamento da osteoporose. Métodos: representantes das diferentes especialidades que estudam e trabalham com os diferentes aspectos da osteoporose participaram deste consenso, no qual estabeleceram estas diretrizes baseados em uma revisão sistemática da literatura buscando evidências científicas consistentes. Os trabalhos foram selecionados pela sua metodologia, desenho, medidas adequadas e validade dos resultados contemplando procedimentos diagnósticos, preventivos e terapêuticos. Resultados: Após extensa discussão os participantes produziram um texto básico sujeito a correções posteriores, e revisões até a aprovação final

Fitoestrogênios: posicionamento do departamento de endocrinologia feminina da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) / Phytoestrogens: position of the department of female endocrinology of the Brazilian Society of Endocrinology and Metabolism

Para avaliar a utilidade dos fitoestrogênios (FE) na terapia de reposição hormonal da menopausa (TRHM), o Departamento de Endocrinologia Feminina da SBEM reuniu um grupo de especialistas para fazer uma revisão bibliográfica e selecionar trabalhos nos quais a metodologia adotada demonstrasse rigor científico. Os FE têm ações estrogênicas e antiestrogênicas, predominantemente sobre os receptores de estrogênios (E) ß, com potência estrogênica muito inferior à do estradiol. O conteúdo de FE nas suas fontes vegetais é variável, dependendo da forma de cultivo, safra, armazenamento e industrialização. Também a conversão dos precursores em fitormõnios ativos no organismo humano tem grande variabilidade individual. A maior parte das pesquisas com FE é realizada in vitro ou com animais de laboratório, nem sempre podendo ser extrapoladas para humanos. Com relação à síndrome do climatério, alguns estudos sugerem discreta melhora dos fogachos, sem modificação do ressecamento vaginal ou das alterações do humor. No metabolismo lipídico, alimentação rica em soja, mas não isoflavonas isoladamente, promove redução do colesterol total, do LDL-col e dos triglicerídeos, mas não elevam o HDL-col, como os E, e podem causar aumento da lipoproteína (a), que os E contribuem para diminuir. Embora alguns estudos de curta duração sugiram aumento da densidade mineral óssea com uso de isoflavonas, não há demonstração de redução de fraturas. Conclui-se que não há evidências convincentes que justifiquem o uso de FE ou alimentação rica em soja como alternativa para a TRHM.