Gestão de riscos como melhoria para a aquisição e distribuição de insulinas pelo SUS / Risk management as an improvement for the acquisition and distribution of insulins by SUS

Objetivo: identificar a melhoria por meio da gestão de risco aplicada aos processos de aquisição e distribuição de insulinas humanas NPH. Método: O estudo foi realizado por etapas: em 1º momento foram realizadas reuniões (Brainstorming) e em 2º momento foi elaborado um formulário eletrônico em forma de questionário sendo mostrado os "eventos" de riscos com os pesos inerentes à probabilidade e ao impacto que geraram o risco inerente aos processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde. Resultados: Considerando os processos houve maior incidência de riscos médios. Não foi apontado risco muito baixo, não foi identificado risco extremo e foram apresentados apenas 02 (dois) riscos altos. Conclusão: A gestão de risco do referido estudo é uma ferramenta de melhoria para os processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde.(AU)

Objective: to identify improvement through risk management applied to the acquisition and distribution processes of NPH human insulins. Method: The study was carried out in stages: in the 1st moment, meetings were held (Brainstorming) and in the 2nd moment, an electronic form was elaborated in the form of a questionnaire, showing the risk "events" with the weights inherent to the probability and impact they generated the risk inherent in the acquisition and distribution processes of NPH and Regular human insulins by the Ministry of Health. Results: Considering the processes, there was a higher incidence of medium risks. No very low risk was indicated, no extreme risk was identified and only 02 (two) high risks were presented. Conclusion: The risk management of the aforementioned study is an improvement tool for the processes of acquisition and distribution of NPH and Regular human insulins by the Ministry of Health.(AU)

Insulinas análogas de ação prolongada comparadas à insulina NPH para tratamento de diabetes mellitus tipo 2 em adultos: revisão rápida / Long-acting basal insulin analogues compared to nph insulin for type 2 diabetes mellitus in adults: rapid review

Tecnologia: Insulinas análogas de liberação prolongada versus insulina NPH (protamina neutra de Hagedorn). Indicação: Tratamento de adultos com diabetes mellitus tipo 2. Pergunta: Há diferenças de efeito nos principais desfechos de eficácia e segurança entre insulinas análogas de liberação prolongada versus insulina NPH no tratamento de pacientes com DM2? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada e incluída uma revisão sistemática. Conclusão: As insulinas análogas (glargina e detemir) não demonstraram superioridade nos desfechos de eficácia e segurança quando comparadas à insulina NPH, não demonstraram redução significativa em relação à mortalidade por todas as causas e complicações secundárias ao DM2. Quando comparadas à insulina NPH, foi observado redução na hipoglicemia confirmada e hipoglicemia noturna a favor das insulinas análogas e na hipoglicemia grave a favor da insulina detemir

Technology: Long-acting insulin analogues versus NPH insulin (human isophane insulin). Indication: Treatment of adults with type 2 diabetes mellitus. Question: Are there effect differences in key efficacy and safety outcomes between long-acting insulin analogues versus NPH insulin in the treatment of DM2 patients? Methods: Rapid review of evidence (overview) of systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: A systematic review was selected and included. Conclusion: Analog insulins (glargine and detemir) did not demonstrate superiority in efficacy and safety outcomes when compared to NPH insulin, did not demonstrate a significant reduction in all-cause mortality and complications secondary to DM2. When compared to NPH insulin, a reduction in confirmed hypoglycemia and nocturnal hypoglycemia in favor of analogue insulins and in severe hypoglycemia in favor of insulin detemir was observed

A prospective, randomized, open label, single-centre study for assessment of safety and effectiveness of recombinant human insulin 30/70 + insulin glulisine compared to recombinant human insulin NPH + regular in the management of type 2 diabetes mellitus patients in the Philippines

Background@#The high prevalence of type 2 diabetes mellitus (T2DM) in the Philippines has burdened the health care system. Therefore, we compared the standard of care Insulin 30/70 + Insulin Glulisine (Arm B) to a traditional insulin regimen NPH Insulin + Regular Insulin (Arm A) to test the concept that both insulin regimens provide comparable effectiveness and safety in real-world practice.@*Methods @#This is a ‘proof-of-concept,’ prospective, randomized, open label pragmatic study of 40 consecutive Filipino T2DM patients from October 2015 to June 2016. The primary endpoint was a reduction in HbA1c at 12 weeks. The secondary endpoints were changes in Fasting Plasma Glucose (FPG), Post Prandial Glucose (PPG), Capillary Blood Sugar (CBS), weight and insulin dose at 12 weeks. ANCOVA and Fisher’s exact tests were used.@*Results @#Patients in treatment arm A showed comparable glycemic control to arm B as measured by reductions in HbA1c (2.89% vs. 2.67%; P = 0.657), FPG (65.94 vs. 46.71 mg/dl; P = 0.57), PPG (76.49 vs. 86.96 mg/dl; P = 0.271) and CBS (115.15 vs. 145.95 mg/dl; P = 0.420). Both treatment arms reported similar weight gain (1.92 vs. 1.22 kg), experienced similar incidence of hypoglycemia (7 vs. 6 patients) and adverse events (AE) (8 vs. 8 patients).@*Conclusion @#The traditional combination of NPH Insulin + Regular Insulin offers comparable glycemic control and tolerance as the standard of care without any new safety signals in the Filipino T2DM population. With a lower price, it can be one of the strategies to reduce the fi nancial burden of antidiabetic treatment.

Factores de riesgo asociados al mal control metabólico en pacientes con diabetes mellitus tratados con insulina / Risk factors associated with poor metabolic control in patients with diabetes mellitus treatedwith insulin

Introducción: la diabetes mellitus (DM) constituye un problema de salud pública prioritario, tanto por su incidencia, prevalencia y la morbimortalidad que de ella derivan. Objetivo: determinar los factores de riesgo asociados al mal control metabólico en pacientes con DM tratados con insulina e internados en la sala de Clínica Médica del Hospital Nacional. Metodología: diseño de casos (diabéticos con mal control metabólico al alta) y controles (diabéticos con buen control metabólico al alta). Muestreo no probabilístico de casos consecutivos. Resultados: ingresaron al trabajo 119 pacientes, con una edad media de 60 años, el 57% de ellos de sexo femenino y el 43% masculino. El tipo de DM predominante fue el tipo 2 (96,5 %). Todos se encontraban en tratamiento con insulina tanto rápida, intermedia y prolongada. El tipo de insulina no influyó sobre el control metabólico. La insulina NPH fue la de uso predominante. El grupo control utilizó menor dosis promedio de insulina. Se analizó los efectos de la hipertensión arterial, la enfermedad renal crónica e infecciones en el control glicémico y ninguna de ellas influyó sobre el control de la misma al alta. Conclusión: el único factor estadísticamente significativo para el buen control metabólico al alta fue el mayor tiempo de internación.

Introduction: diabetes mellitus (DM) is a priority public health problem, both for its incidence, prevalence, morbidity and mortality that derive from it. Objective: to determine the risk factors associated with poor metabolic control in patients with DM treated with insulin and admitted to the Internal Medicine Department of the Hospital Nacional. Metodology: cases design (diabetics with poor metabolic control at discharge) and control group. (Diabetics with metabolic control at discharge).Non-probabilistic sampling of consecutive cases.Results: 119 patients were recruited, with an average age of 60 years, 57% of them female and 43% male. The predominant type 2 DM was (96.5%). All were treated with both fast, intermediate and prolonged insulin. The type of insulin had no influence on metabolic control. NPH insulin was the predominant use. The control group used insulin doses lower than average. The effect of hypertension was analyzed, chronic kidney disease and infections in glycemic control and none of them influenced the control at discharge. Conclusion: the only statistically significant factor for good metabolic control at discharge was a longer hospital stay.

Comportamiento de hemoglobina glicosilada y frecuencia de hipoglicemias en diabéticos tipo 2 tratados con insulina glargina o NPH / Glycosylated hemoglobin behavior and frequency of hypoglycemia in type 2 diabetics treated with insulin glargine or NPH

Objetivo: Evaluar comportamiento de hemoglobina glicosilada (HbA1c) y frecuencia de hipoglicemias sintomáticas con esquema basal con insulina NPH comparado con insulina glargina en diabéticos tipo 2 (DM2), atendidos en un programa de riesgo cardiovascular. Materiales y métodos: Estudio observacional de cohorte retrospectivo. Se revisaron 613 historias clínicas de pacientes con DM2 manejados con esquema basal con insulina NPH o glargina, de los cuales 76 cumplieron los criterios de inclusión. Se revisó historia clínica al momento de inclusión (consulta No. 1), a los seis (consulta No. 2) y a los doce meses (consulta No. 3). Resultados: Se analizaron 13 pacientes del grupo glargina y 63 del grupo NPH (edad 64,9 [± 10,9 años], 54 porciento mujeres). En la consulta No. 1 el promedio de HbA1c fue 7.8 porciento en grupo con NPH y 7.5 porciento en grupo glargina. Al final del seguimiento los niveles de HbA1c fueron 7.5 porciento en grupo NPH y 7.9 porciento en grupo glargina (p= 0.4). Los eventos de hipoglucemia fueron 3 en la primera consulta y 4 en la tercera, todos recibían NPH. En la segunda consulta se presentaron 5 eventos en pacientes con NPH y 1 caso con glargina (p=0.9). Las variables más fuertemente asociadas con niveles bajos de HbA1c fueron enfermedad renal crónica y sexo femenino. Conclusiones: Los pacientes con DM2 de este estudio no presentaron diferencia estadísticamente significativa en valores de HbA1c de acuerdo al tipo de insulina recibida.Se observó menor frecuencia de hipoglucemias en pacientes que utilizaban insulina glargina sin encontrarse diferencia estadísticamente significativa.

To evaluate performance of glycosylated hemoglobin (HbA1c) and frequencyof symptomatic hypoglycemia scheme with basal insulin glargine compared toNPH insulin in type 2 diabetics (DM2), served in a program of cardiovascularrisk. Materials and methods: Observational retrospective cohort. 613 medicalrecords of patients with DM2 managed scheme with basal insulin NPHor glargine, of which 76 met the inclusion criteria were reviewed. medicalrecords were reviewed at the time of inclusion (see No. 1), six (see No. 2)and twelve months (see No. 3). Results: 13 patients in the glargine group and63 in the NPH group (age 64.9 [± 10.9 years], 54% female) were analyzed.The consultation No. 1 mean HbA1c was 7.8% with NPH group and 7.5% inglargine group. At follow-up HbA1c levels were 7.5% in NPH group and 7.9%in glargine group (p = 0.4). Hypoglycemic events were 3 in the first visit and 4in the third, all received NPH. In the second consultation five events occurredin patients with NPH and 1 case with glargine (p = 0.9). The variables moststrongly associated with low levels of HbA1c were chronic kidney disease andwomen. Conclusions: Patients with DM2 of this study showed no statisticallysignificant difference in HbA1c values according to the type of insulinreceived. Lower frequency of hypoglycemia in patients using insulin glargineno statistically significant difference was observed.

Diabetes Mellitus tipo 2 con tendencia a la cetosis: Caso clínico / Ketosis prone type 2 diabetes (KPD)

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Biphasic insulin aspart 30 improved glycemic control in Chinese patients with type 2 diabetes poorly controlled on oral glucose-lowering drugs: a subgroup analysis of the A₁chieve study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials, while results from clinical practice remain limited. This subgroup analysis was to provide such findings from a large-scale non-interventional study.</p><p><b>METHODS</b>A1chieve was a multinational, prospective, open-label, non-interventional, 24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia, Africa, Europe, and Latin America. After physician had taken the decision to use this insulin, any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible. Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control were collected at baseline, week 12 and 24. This is a report of a Chinese subgroup analysis from the A1chieve study.</p><p><b>RESULTS</b>Totally, 4 100 patients constituted this subgroup. No serious adverse drug reactions were reported. Rates of total, major, nocturnal hypoglycemic events (events/patient per year) were 1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively. Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%, reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5 mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6 mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001).</p><p><b>CONCLUSION</b>In this subgroup analysis of the A1chieve study, biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.</p>

Clinical experience with BIAsp 30: Results from the Philippine cohort of the global a1chieve study

OBJECTIVE: To evaluate the safety, effectiveness and health-related quality of life (HRQoL) parameters of A1chieve study participants in the Philippine cohort, who were treated with BIAsp 30.METHODOLOGY: A1chieve is a non-interventional, six-month, observational study of 66,726 people with type 2 diabetes mellitus (T2DM), including both insulin users and non-insulin users, started on insulin detemir, insulin aspart, or BIAsp 30 in 28 countries across four continents. The present study evaluates the safety, effectiveness and HRQoL in 1,252 subjects from the Philippine cohort of the A1chieve study who were treated with BIAsp 30.RESULTS: At baseline, the mean age, duration of diabetes and mean BMI were found to be 55.5±11.7 years, 7.2 ± 5.6 years and 25.4 ± 5.3 kg/m2, respectively. Seventy-eight percent (78%) of subjects were insulin naïve and 22% were prior insulin users. At baseline, glycemic control was poor (HbA1c = 9.9%) in the entire cohort. Overall there was a 2.7% reduction in mean HbA1c and 44.2% subjects achieved the HbA1c target of CONCLUSION: BIAsp 30 is safe and efficacious for initiating and intensifying insulin therapy for Filipino T2DM patients.

Insulinas análogas de longa ação Diabetes Mellitus tipo II / Analog Long-acting Insulins Type II Diabetes Mellitus

A DOENÇA: Diabetes Mellitus (DM), de acordo com a Organização Mundial da Saúde (OMS), é o termo que descreve uma desordem metabólica de etiologia múltipla, caracterizada por hiperglicemia crônica e distúrbios no metabolismo de carboidratos, lipídios e proteínas resultantes de defeitos na secreção de insulina, na ação da insulina ou em ambos. Para a Sociedade Brasileira de Diabetes (SDB), a classificação atual do DM deve levar em conta a sua etiologia. Assim, convergente com associações internacionais e com a própria OMS, a Diabetes Mellitus é classificada em quatro classes clínicas: DM tipo 1, DM tipo 2, outros tipos específicos de DM e DM gestacional. O diabetes tipo 2 (DM2) é a forma mais presente destas manifestações, atingindo mais de 90% dos casos e caracteriza-se por defeitos na ação e secreção de insulina. Desenvolve-se geralmente em adultos e tem sido relacionada à obesidade, falta de atividade física e hábitos alimentares não saudáveis. TRATAMENTO: No tratamento do diabetes tipo 2, é recomendado um plano terapêutico que vise o controle glicêmico e a prevenção de complicações crônicas decorrentes da doença. Para isso, este plano deve englobar não apenas o tratamento farmacológico, mas medidas que conduzam à mudança de estilo vida, com orientação nutricional e atividade física, pois existem comprovadas evidências do impacto do tratamento não farmacológico na melhoria de parâmetros importantes para a doença, como redução da hemoglobina glicada, sensibilidade à insulina, diminuição do colesterol, perda de peso e gordura visceral, diminuição do risco de doença cardiovascular e melhora da qualidade de vida. Em relação ao tratamento farmacológico, atualmente está disponível no SUS para o tratamento da DM2 as insulinas de ação intermediária (insulina NPH) e de ação rápida (insulina regular), além de medicamentos hipoglicemiantes (biguanidas, derivados da uréia, sulfonamidas). A TECNOLOGIA: Insulinas análogas de longa ação: As insulinas análogas de longa ação são resultantes de mudanças estruturais na molécula de insulina humana, obtida a partir da tecnologia do DNA-recombinante, com o objetivo de estender a duração do efeito e diminuir a variação intra-individual. São consideradas alternativas terapêuticas para o controle glicêmico basal, possuindo o mesmo objetivo da insulina NPH. EVIDÊNCIAS CIENTÍFICAS: A Secretaria-Executiva da CONITEC realizou busca na literatura por artigos científicos, com o objetivo de localizar a melhor evidência científica disponível sobre o tema. Considerando o grande número de publicações sobre o tema, restringiram-se os resultados apenas às revisões sistemáticas disponíveis, entendendo que esta é a melhor evidência para avaliar a eficácia de uma tecnologia para tratamento. A busca por evidências sobre a eficácia das insulinas glargina e detemir em comparação à insulina NPH no controle do DM2 foi realizada nas bases de dados MEDLINE (via Pubmed), Cochrane Library (via Bireme) e Centre for Reviews and Dissemination. CONSIDERAÇÕES FINAIS: A evidência atualmente disponível sobre eficácia e segurança das insulinas análogas de longa ação (glargina e detemir) no tratamento do diabetes mellitus tipo 2 não mostrou que esta fosse superior à insulina NPH em relação ao controle glicêmico medido pela hemoglobina glicosilada (HbA1c), glicemia em jejum, redução da hipoglicemia severa e presença de efeitos adversos (segurança). No que diz respeito à menor ocorrência de hipoglicemia noturna, os resultados tendem a favorecer as insulinas análogas, mas deve-se avaliar o real benefício clínico frente à diferença aferida nos estudos. Deve-se, também, considerar as limitações metodológicas dos estudos, como a avaliação subjetiva e as diferentes definições para o episódio de hipoglicemia, o desenho aberto dos estudos, o potencial conflito de interesse de alguns autores e estudos patrocinados pelo produtor farmacêutico. Além disso, o curto período de seguimento dos estudos impede a mensuração de efeitos primordiais (morbidade, mortalidade, complicações em longo prazo), impossibilitando a medida da real relevância clínica das insulinas análogas de longa ação em relação ao tratamento convencional (insulina NPH). Assim, observa-se que a literatura científica internacional aponta na direção de que não há evidências de que as insulinas análogas trazem melhoras significativas nas condições de saúde dos pacientes e que o benefício clínico associado ao uso das insulinas análogas é ainda discreto frente aos custos relacionados ao tratamento. As insulinas análogas de longa ação (detemir e glargina) parecem não ser inferiores à insulina humana NPH, mas também não está claro se apresentariam alguma superioridade em benefício clínico. O impacto orçamentário também se apresentou como um obstáculo na incorporação destas insulinas análogas, quando consideramos o grande aporte de recursos necessários para a sua introdução e o seu benefício clínico incerto frente à insulina NPH. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 24ª reunião ordinária do plenário do dia 09/04/2014, por unanimidade, ratificaram a deliberação de não recomendar a incorporação das insulinas análogas de longa ação (detemir e glargina) para o tratamento do Diabetes Mellitus tipo II. DECISÃO: PORTARIA Nº 30, de 4 de setembro de 2014 - Torna pública a decisão de não incorporar as insulinas análogas para diabetes mellitus tipo II no âmbito do Sistema Único de Saúde - SUS.

Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study

BACKGROUND: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS: The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS: Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values < or =6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). CONCLUSION: Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.

Safety and Efficacy of Modern Insulin Analogues

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

IGF-I, leptina, insulina e proteínas associadas à qualidade do plasma seminal: ação local / IGF-I, leptine, insulin and proteins associated to seminal plasma quality: local action

É possível que a expressividade de alguns elementos do plasma seminal dos bovinos, como proteínas e hormônios, possa servir como marcadores para sêmen de alta ou baixa fertilidade. Vários estudos têm demonstrado a associação de proteínas do plasma seminal com a fertilidade de touros. Dentre as mais estudadas, destacam-se aquelas com afinidade à heparina, que exercem importantes papéis na capacitação espermática e na reação acrossômica. Alguns fatores endócrinos e/ou locais, podem estar associados à expressividade e/ou função destas proteínas, auxiliando nas condições espermáticas favoráveis à fecundação. Dentre estes, destacam-se a insulina, a leptina e o fator de crescimento semelhante à insulina do tipo I. Assim sendo, evidenciam diferenças entre animais, estando associados à estrutura e as condições metabólicas da célula espermática, auxiliando na determinação da qualidade do plasma seminal. Desta maneira, o estudo das proteínas do plasma seminal asociado à condição metabólica destes hormônios, presentes neste meio, pode servir como importante parâmetro de avaliação da condição reprodutiva do macho

It is possible that the expression of some elements in seminal plasma, such as proteins and hormones, may act as markers of quality. Several studies have demonstrated an association of seminal plasma proteins with fertility. Among the most studied, there are the proteins with affinity to heparin, which play an important role in sperm capacitation and acrosome reaction. Some endocrine factors and/or locals may be associated with the expression and function of these proteins, aiding in sperm condition conducive to fertilization. Among them stand out as insulin, leptin and growth factor insulin-like type I. Thesefactors may highlight the differences between these animals because they are associated with the metabolic condition and structure of sperm cells, aiding in determining the quality of seminal plasma. Thus, the study of seminal plasma proteins associated with the metabolic condition of these hormones are present in this medium can serve as a new parameter for assessment of male reproductive condition...

Switching from human insulin to biphasic insulin aspart 30 treatment gets more patients with type 2 diabetes to reach target glycosylated hemoglobin < 7%: the results from the China cohort of the PRESENT study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The clinical importance of glycaemic control in patients with diabetes has been well established. This study aimed to explore twice-daily biphasic insulin aspart 30 (BIAsp 30) for insulin initiation in patients with type 2 diabetes mellitus (T2DM) who had poor glycaemic control with human insulins (HIs). We use data from a Chinese cohort of the PRESENT study.</p><p><b>METHODS</b>In the 3-month study, Chinese subjects with T2DM started insulin therapy with BIAsp 30 in routine care. Glycaemic control was measured by glycosylated hemoglobin (HbA(1C)), fasting plasma glucose (FPG) and posting plasma glucose (PPG). The safety assessment included hypoglycaemia and other adverse events.</p><p><b>RESULTS</b>A total of 1989 subjects previously treated with His were switched to BIAsp 30 for 3-month treatment. Mean HbA(1C), FPG and PPG were significantly improved after the therapy. The overall rate of hypoglycaemia decreased at the end of the trial except for the patients previously treated with long-acting insulin. Most of the events were minor and diurnal hypoglycaemia. Only one serious adverse drug reaction (SADR), a local hypersensitivity, was reported. The majority of the patients (> or = 96.7%) and physicians (> or = 84.7%) were either satisfied or very satisfied with the treatment using BIAsp 30 compared with previous HI therapy.</p><p><b>CONCLUSION</b>The BIAsp 30 treatment improved both glycaemic control and patients' satisfaction without increasing hypoglycaemia in T2DM subjects inadequately controlled by His.</p>

Comparison on efficacy and safety of two regimens for treatment of type 2 diabetes mellitus: glargine plus metformin versus neutral protamine hagedorn plus metformin / 生物医学工程学杂志

This is a work aimed to investigate the efficacy and safety of the combination of metformin with glargine or with neutral protamine Hagedorn in treatment of type 2 diabetes mellitus. Sixty such patients with poor glycemic control by oral antidiabetic drugs were included and divided into group A and group B. Thirty patients in group A were treated with glargine and metformin, and the other 30 patients in group B were treated with neutral protamine Hagedorn and metformin for 12 weeks. Fasting plasma glucose (FPG), postprandial glucose(PPG) and HbA1c were measured before and after the treatment. Hypoglycemia was also noted. At the end of the study, the levels of FPG, PPG and HbAlc were significantly lower than the baseline levels in the two groups (P < 0.05). At the 12th week, the percentage of HbAlc < 7% in group A was 53.3% and that in group B was 40.0%; statistically, there was no significant difference (P > 0.05). After the end of the treatment, there was no significant difference in that the percentage of HbA1c < 7% was 70.6% in group A and 62.5% in group B; the two groups' HbA1c levels were > or = 7%-9% at the baseline (P > 0.05). No sigificant difference in respect to the incidence rate of hypoglycemia in the two groups was noted (P > 0.05). In the cases of type 2 diabetes mellitus with poor glycaemic control by oral antidiabetic drug, glucose and HbA1c can be lowered further by the combination of metformin with glargine or with neutral protamine Hagedorn, the incidence rate of hypoglycemia is low. Metformin plus glargine or plus neutral protamine Hagedorn is a safe and effective therapeutic choice for type 2 diabetes mellitus cases with poor glycaemic control; moreover, metformin plus neutral protamine is a cheaper and effective choice.

Utilização da insulina glargina em crianças menores de oito anos de idade / Use of insulin glargine in type 1 diabetes children with less than eight years old

OBJETIVOS: Avaliar prospectivamente a eficácia e a segurança da insulina glargina no controle metabólico de crianças com diabetes melito tipo 1 (DMT1) com menos de oito anos de idade. MÉTODOS: Foram avaliados 19 meninos e 11 meninas. Antes de iniciar a insulina glargina, todas as crianças foram colocadas em tratamento intensivo com insulina NPH e insulina asparte durante três meses. Posteriormente, os pacientes foram acompanhados por 12 meses para o tratamento com glargina. Todos os pacientes realizavam medidas da glicemia capilar 3-7 vezes ao dia. Desfechos principais: controle metabólico por meio da hemoglobina glicada (A1c); ocorrência de hipoglicemia leve (glicemia capilar < 60 mg/dL) e ocorrência de hipoglicemia grave (perda ou alteração na consciência, convulsão ou necessidade de intervenção médica). RESULTADOS: A1c média no início do estudo foi 8,68 por cento, semelhante ao valor obtido ao final dos 12 meses de tratamento com glargina (8,64 por cento; p = 0,82). A frequência de hipoglicemia leve às 3 horas da madrugada foi 1,43/3 meses por paciente com insulina NPH e de 0,28/3 meses por paciente com insulina glargina (p < 0,007). Em relação à hipoglicemia severa, houve uma diferença favorável à glargina: 0,008 versus 0,56 eventos/3 meses por paciente (p < 0,002). CONCLUSÕES: O uso da insulina glargina no tratamento de crianças com DMT1 foi considerado tão eficaz quanto o uso da NPH, apresentando, no entanto, melhor perfil de segurança caracterizado pelo menor risco de hipoglicemia noturna e severa.

OBJECTIVES: To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old. METHODS: Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention). RESULTS: Mean A1C at the study entry was 8.68 percent and after 12 months of glargine, was 8.64 percent (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002). CONCLUSIONS: The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

A evolução da insulinoterapia no diabetes melito tipo 1: [revisão] / Insulin therapy for type 1 diabetes mellitus: past and present: [review]

A descoberta da insulina foi o grande marco da história do diabetes melito e a grande conquista para o seu tratamento. A primeira insulina disponibilizada foi a regular. Na seqüência, Hagedorn acrescentou a protamina à insulina, criando, assim, a insulina NPH. Na década de 1950 foi sintetizada uma insulina desprovida de protamina, denominada insulina lenta. Com o advento da biologia molecular, sintetizou-se, via DNA recombinante, a insulina humana sintética. Mais recentemente, foram disponibilizados vários tipos de análogos de insulina que permitiram o melhor controle metabólico dos pacientes. O tratamento do diabetes melito tipo 1, além do processo educacional, incluindo a prática regular de atividades físicas e orientações dietéticas, resume-se na substituição plena de insulina de longa e curta durações de ação, de maneira individualizada, de acordo com a experiência do médico-assistente. No diabetes melito tipo 1, a preferência é pelas insulinas de menor variabilidade, por meio do esquema basal/bólus ou pelas bombas de infusão contínua de insulina subcutânea com o objetivo de mimetizar a liberação fisiológica de insulina pelas células-beta.

The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells.