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).

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil.

BACKGROUND: Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients. METHODS: This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers 'occasionally' and 'never' to the question 'Do you have symptoms when you have a low sugar level?' denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from 'not afraid at all' to 'absolutely terrified'. RESULTS: From 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1DM and 5.4 ± 3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%). CONCLUSIONS: Referred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.

Clinical inertia on insulin treatment intensification in type 2 diabetes mellitus patients of a tertiary public diabetes center with limited pharmacologic armamentarium from an upper-middle income country.

BACKGROUND: Clinical inertia is related to the difficulty of achieving and maintaining optimal glycemic control. It has been extensively studied the delay of the period to insulin introduction in type 2 diabetes mellitus (T2DM) patients. This study aims to evaluate clinical inertia of insulin treatment intensification in a group of T2DM patients followed at a tertiary public Diabetes Center with limited pharmacologic armamentarium (Metformin, Sulphonylurea and Human Insulin). METHODS: This is a real life retrospective record based study with T2DM patients. Demographic, clinical and laboratory characteristics were reviewed. Clinical inertia was considered when the patients did not achieve the individualized glycemic goals and there were no changes on insulin daily dose in the period. RESULTS: We studied 323 T2DM patients on insulin therapy (plus Metformin and or Sulphonylurea) for a period of 2 years. The insulin daily dose did not change in the period and the glycated hemoglobin (A1c) ranged from 8.8 + 1.8% to 8.7 ± 1.7% (basal vs 1st year; ns) and to 8.5 ± 1.8% (basal vs 2nd year; p = 0.035). The clinical inertia prevalence was 65.8% (basal), 61.9% (after 1 year) and 58.2% (after 2 years; basal vs 1st year vs 2nd year; ns). In a subgroup of 100 patients, we also studied the first 2 years after insulin introduction. The insulin daily dose ranged from 0.22 ± 0.12 to 0.32 ± 0.24 IU/kg of body weight/day (basal vs 1st year; p < 0.001) and to 0.39 ± 0.26 IU/kg of body weight/day (basal vs 2nd year; p < 0.05). The A1c ranged from 9.6 + 2.1% to 8.6 + 2% (basal vs 1st year; p < 0.001) and to 8.7 + 1.7% (1st year vs 2nd year; ns). The clinical inertia prevalence was 78.5% (at the moment of insulin therapy introduction), 56.2% (after 1 year; p = 0.001) and 62.2% (after 2 years; ns). CONCLUSION: Clinical inertia prevalence ranged from 56.2 to 78.5% at different moments of the insulin therapy (first 2 years and long term) of T2DM patients followed at a tertiary public Diabetes Center from an upper-middle income country with limited pharmacologic armamentarium.

Diabetes mellitus no Brasil: características clínicas, padrão de tratamento e custos associados ao cuidado da doença / Diabetes Mellitus in Brazil: clinical characteristics, standard treatment choice and cost

Objetivo: Descrever a utilização de recursos de saúde associados ao tratamento do Diabetes Mellitus tipo 2 (DM2) no sistema público de saúde brasileiro, assim como o padrão de tratamento e seus eventos adversos, a ocorrência de complicações vasculares e o controle metabólico nos pacientes. Métodos: Estudo observacional, retrospectivo, conduzido em 4 centros do Sistema Único de Saúde envolvendo pacientes com DM2. Os dados foram coletados dos prontuários médicos de setembro a dezembro de 2013. Foi conduzida análise descritiva considerando três faixas de duração da doença desde o seu diagnóstico e a estratificação dos pacientes de acordo com o período recordatório e presença de complicações vasculares. Resultados: 161 pacientes foram analisados. Os principais esquemas terapêuticos utilizados foram a combinação de metformina, insulina NPH e insulina regular; de glibenclamida e metformina; e metformina isolada. A associação metformina e insulina apresentou maior frequência de eventos adversos (28,9%) e a glibenclamida, metformina e insulina, menor frequência (5,7%). A maioria dos pacientes mostrou complicações microvasculares, sendo nefropatia e neuropatia frequentes em todos os estratos analisados. Em pacientes com DM2 avançado (≥ 15 anos de duração), a retinopatia mostrou-se prevalente. A frequência de eventos macrovasculares variou de 21,3% a 37,9% entre os grupos, sendo a doença coronariana a mais frequente. Um custo total médio de R$ 931,88±1.400,75 por paciente foi observado para os pacientes sem complicações vasculares e de R$ 1.212,37±1.012,38 para aqueles com complicações. Conclusão: Informações relevantes sobre o manejo de pacientes brasileiros com DM2 foram descritas, sugerindo alta frequência de complicações vasculares e maiores custos associados a elas.

Objective: The aim of this study is to describe the use of public health resources to Type 2 Diabetes Mellitus (T2DM) and its costs in Brazil. Furthermore, we describe the standard treatment choice and its related adverse events as well as patients' metabolic control and vascular complications. Methods: This observational and retrospective study was conducted in four public health centers from Brazilian Public Health System (SUS); a secondary assistance level for long-term treatment for outpatients with T2DM. Data were collected from medical records from September to December 2013. A descriptive analysis is available for three groups according to time of disease since diagnosis. The recall and vascular complications were also considered. Results: 161 patients were studied. The most frequent treatments were metformin in monotherapy, metformin + NPH insulin + regular insulin and metformin + glibenclamide. Metformin + insulin therapy had the highest rate of adverse events (28.9%), while glibenclamide + metformin + insulin therapy, the lowest rate (5.7%). The majority of patients developed microvascular complications, specially nephropathy and neuropathy. Retinopathy was the most frequent complication for the group of patients with end stage T2DM (≥ 15 years). The frequency of macrovascular events ranged from 21.3% to 37.9% between groups. Coronary disease was the most frequent macrovascular complications. The mean cost per patient was R$ 1.212,37±1.012,38 for patient group presenting vascular complications and R$ 931,88±1.400,75 for the group not presenting complications. Conclusion: We describe current use of public health resources regarding T2DM treatment in Brazil, as well as T2DM treatment´s characteristics.

The cost of type 2 diabetes in Brazil: evaluation of a diabetes care center in the city of São Paulo, Brazil.

BACKGROUND: The worldwide increase of diabetes, a long duration, slow progression disease, impacts health care costs. The aim of this study was to estimate, from the society's perspective, the annual cost per patient with Type 2 Diabetes (T2DM) at a specialized, outpatient center in the city of São Paulo, capital of São Paulo state, Brazil. METHODS: Data from 209 patients were collected during the years 2009 and 2010 in a São Paulo diabetes care center which is part of the tertiary sector of SUS, Brazil's National Health Care System. Data were collected by means of interviews and reviews of medical charts, and the quality of life was appraised using the SF36-v2 questionnaire. Direct medical costs were divided in five categories: 1) medication; 2) laboratory tests; 3) hospitalizations and procedures; 4) reactive strips for capillary blood glucose monitoring; and 5) medical consultations. Direct non-medical costs referred to transportation of patient and companion for treatment. Indirect costs included early retirements, sick leave and absenteeism in the workplace. Statistical analysis of the data was performed by the SPSS software, version 17.0. RESULTS: Our sample comprised 122 women (58%) and 87 men (42%), with mean age of 63 years and average diabetes duration of 13 years. The mean annual cost was US$ 1,844 per patient, out of which US$ 1,012 corresponded to direct costs (55%) and US$ 831 to indirect costs (45%). From the direct medical costs, medications accounted for the greatest proportion (42%), followed by reactive strips (27%), hospitalizations and procedures (14%), laboratory tests and image examinations (7%), as well as medical consultations (4%). Non-medical costs (transportation) corresponded to 7% of the total direct costs. Besides, the results indicated that men have better quality of life than women. CONCLUSION: This study demonstrated a high T2DM cost in Brazil, considering the governmental per capita expenses in health care, which accounted for US$ 466 in 2010 (World Health Statistics 2013 96-104 2013). Taking into account the high prevalence of the disease (IDF Diabetes Atlas. 5th edition. 29-48 2012), this survey recommends the enforcement of policies for the prevention of diabetes and its complications, and urges for better allocation of healthcare resources.

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation / Seguimento clínico de dois pacientes brasileiros com MODY-glicoquinase (MODY2) e descrição de uma nova mutação

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Mutações no gene da glicoquinase (GCK) são determinantes de uma forma de diabetes monogênico denominada de MODY2 (maturity-onset diabetes of the young, tipo 2). O padrão clínico dessa forma de distúrbio glicêmico é bastante estável, com hiperglicemia leve, geralmente não progressiva. Intervenções farmacológicas raramente são necessárias e complicações crônicas secundárias ao diabetes são infrequentes. Descrevemos o acompanhamento clínico de dois casos de MODY2 com duas mutações diferentes, uma no éxon 7, p.Glu265Lys (c.793 G>A) já descrita anteriormente, e outra inédita no éxon 2 p.Ser69Stop (c. 206C>G). A evolução clínica de ambos os casos demonstra uma semelhança no padrão metabólico dessa forma de diabetes ao longo dos anos. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation.

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years.

Consensus report: the current role of self-monitoring of blood glucose in non-insulin-treated type 2 diabetes.

The Coalition for Clinical Research--Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20-21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the group's final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that: SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.

Conducting cost-effectiveness analyses of type 2 diabetes in low- and middle-income countries: can locally generated observational study data overcome methodological limitations?

In low- and middle-income countries, the high personal and economic burden of type 2 diabetes is further compounded by inadequate resources for diabetes care when compared with high-income countries. Health technology assessments (HTAs) aim to inform policy decision makers in their efforts to achieve more effective allocation of resources by providing evidence-based input on new technologies. Within the hierarchy of evidence, randomized controlled trials (RCTs) remain the 'gold standard' used to inform HTAs, but are limited by poor external validity (ie, generalizability to real-world populations). Unlike RCTs, observational studies are able to enrol broader patient populations, but their design renders such studies vulnerable to confounding factors and selection bias. However, it is increasingly recognized that observational studies can complement RCTs by supporting and extending efficacy findings from RCTs to real-world clinical practice, particularly across geographical populations. They can also provide locally relevant baseline and disease natural history data to populate health economic models. Thus, observational data are likely to be of considerable informative value to policy makers in developing countries reaching decisions on diabetes care within an environment of scarce resources.

Prevalence and correlates of inadequate glycaemic control: results from a nationwide survey in 6,671 adults with diabetes in Brazil.

Diabetes is a significant public health burden on the basis of its increased incidence, morbidity, and mortality. This study aimed to estimate the prevalence of inadequate glycaemic control and its correlates in a large multicentre survey of Brazilian patients with diabetes. A cross-sectional study was conducted in a consecutive sample of patients aged 18 years or older with either type 1 or type 2 diabetes, attending health centres located in ten large cities in Brazil (response rate = 84%). Information about diabetes, current medications, complications, diet, and satisfaction with treatment were obtained by trained interviewers, using a standardized questionnaire. Glycated haemoglobin (HbA(1c)) was measured by high-performance liquid chromatography in a central laboratory. Patients with HbA(1c) > or = 7 were considered to have inadequate glycaemic control. Overall 6,701 patients were surveyed, 979 (15%) with type 1 and 5,692 (85%) with type 2 diabetes. The prevalence of inadequate glycaemic control was 76%. Poor glycaemic control was more common in patients with type 1 diabetes (90%) than in those with type 2 (73%), P < 0.001. Characteristics significantly associated with improved glycaemic control included: fewer years of diabetes duration, multi professional care, participation in a diabetes health education program, and satisfaction with current diabetes treatment. Despite increased awareness of the benefits of tight glycaemic control, we found that few diabetic patients in Brazil met recommended glycaemic control targets. This may contribute to increased rates of diabetic complications, which may impact health care costs. Our data support the public health message of implementation of early, aggressive management of diabetes.

[Clinical heterogeneity and coexistence of diabetic neuropathies: difference and similarities between types 1 and 2 diabetes mellitus]. / Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2.

OBJECTIVE: To evaluate the heterogeneity and the coexistence of diabetic neuropathy (DNP) in type 1 (T1DM) and 2 (T2DM) diabetes mellitus. METHODS: 74 T2DM and 20 T1DM patients were evaluated according to age (years), time from diagnosis of diabetes (TDD, years), body mass index (BMI, kg/m(2)), HbA1c and DNP type (American Diabetes Association criteria). RESULTS: T1DM was younger (32.7 +/- 11.0 versus 56.9 +/- 10.3; p = 0.0001), leaner (BMI: 23.6 +/- 3.85 versus 28.4 +/- 5.3; p = 0.0005) and they had longer TDD (17.1 +/- 9.7 versus 10.4 +/- 6.8; p = 0.003). Cardiovascular autonomic neuropathy (CAN) (60% versus 32.4%; p = 0.02) and its coexistence with polyneuropathy (PN) (62.5% versus 33.3%; p = 0.03) were more common in T1DM. Chronic painful polyneuropathy (CPP) was more prevalent in T2DM (60.8% versus 30.0%; p = 0.009). Logistic regression showed HbA1c as an independent variable related to PN (p = 0.04) in both groups. TDD (p = 0.03) and CPP (p = 0.003) were related to CAN in T1DM. Age (p = 0.0004) was related to CPP in T2DM. CONCLUSIONS: The DNP have shown a heterogeneity distribution in type 1 and type 2 diabetes mellitus. The related factors to different phenotypes of this complication, apart from hyperglycemia, may be variable between these two types of diabetes mellitus.

Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2 / Clinical heterogeneity and coexistence of diabetic neuropathies: difference and similarities between types 1 and 2 diabetes mellitus

OBJETIVO: Estudar a heterogeneidade e a coexistência das neuropatias no diabetes melito tipos 1 (DMT1) e 2 (DMT2). MÉTODOS: Foram avaliados 74 DMT2 e 20 DMT1 em relação à idade (anos), tempo de diagnóstico do DM (TDDM, em anos), índice de massa corpórea (IMC, kg/m²), HbA1c e tipo de neuropatia (critérios da American Diabetes Association). RESULTADOS: DMT1 era mais jovem (32,7 ± 11 versus 56,9 ± 10,3; p = 0,0001), com maior TDDM (17,1 ± 9,7 versus 10,4 ± 6,8; p = 0,003) e menor IMC (23,6 ± 3,8 versus 28,4 ± 5,3; p = 0,0005). A neuropatia autonômica cardiovascular (NAC) (60 por cento versus 32,4 por cento; p = 0,02) e a coexistência desta com polineuropatia (PND) (62,5 por cento versus 33,3 por cento; p = 0,03) foram mais prevalentes no DMT1; a PND dolorosa crônica (PNDDC) (60,8 por cento versus 30,0 por cento; p = 0,009) o foi no DMT2. A HbA1c (p = 0,04) foi preditiva de PND em ambos os grupos. O TDDM (p = 0,03) e a PNDDC (p = 0,003) foram preditivos de NAC no DMT1. A idade (p = 0,0004) teve valor preditivo para PNDDC no DMT2. CONCLUSÕES: As neuropatias apresentam distribuição heterogênea no DMT1 e no DMT2. Com exceção do controle glicêmico, os fatores relacionados a essa complicação diferem de acordo com o tipo de diabetes.

OBJECTIVE: To evaluate the heterogeneity and the coexistence of diabetic neuropathy (DNP) in type 1 (T1DM) and 2 (T2DM) diabetes mellitus. METHODS: 74 T2DM and 20 T1DM patients were evaluated according to age (years), time from diagnosis of diabetes (TDD, years), body mass index (BMI, kg/m²), HbA1c and DNP type (American Diabetes Association criteria). RESULTS: T1DM was younger (32.7 ± 11.0 versus 56.9 ± 10.3; p = 0.0001), leaner (BMI: 23.6 ± 3.85 versus 28.4 ± 5.3; p = 0.0005) and they had longer TDD (17.1 ± 9.7 versus 10.4 ± 6.8; p = 0.003). Cardiovascular autonomic neuropathy (CAN) (60 percent versus 32.4 percent; p = 0.02) and its coexistence with polyneuropathy (PN) (62.5 percent versus 33.3 percent; p = 0.03) were more common in T1DM. Chronic painful polyneuropathy (CPP) was more prevalent in T2DM (60.8 percent versus 30.0 percent; p = 0.009). Logistic regression showed HbA1c as an independent variable related to PN (p = 0.04) in both groups. TDD (p = 0.03) and CPP (p = 0.003) were related to CAN in T1DM. Age (p = 0.0004) was related to CPP in T2DM. CONCLUSIONS: The DNP have shown a heterogeneity distribution in type 1 and type 2 diabetes mellitus. The related factors to different phenotypes of this complication, apart from hyperglycemia, may be variable between these two types of diabetes mellitus.

A importância da hemoglobina glicada (A1c) para a avaliação do controle glicêmico em pacientes com diabetes mellitus: aspectos clínicos e laboratoriais

Posicionamento oficial de 2004 do grupo interdisciplinar de diferentes sociedades médicas sobre a avaliação do controle glicêmico.

Diabetic cardiovascular autonomic neuropathy: risk factors, clinical impact and early diagnosis.

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.

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

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.

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce / Diabetic cardiovascular autonomic neuropathy: risk factors, clinical impact and early diagnosis

A neuropatia autonômica cardiovascular (NAC) constitui uma das complicações de maior repercussão clínica do diabete melito (DM) e, ao mesmo tempo, está entre as menos diagnosticadas. Nesta revisão, são discutidos os principais fatores de risco para o desenvolvimento e a progressão da NAC nos pacientes com DM, a história natural da neuropatia autonômica e seu impacto na doença cardiovascular do DM, bem como os testes para o diagnóstico precoce e o estadiamento da NAC na prática clínica. A pesquisa bibliográfica teve como base dois bancos de dados: Medline e Tripdatabase, com os seguintes descritores: diabetic cardiovascular autonomic neuropathy e cardiovascular autonomic neuropathy and diabetes. Os artigos de 1998 a 2007 em inglês e alemão foram selecionados. A NAC em estágios iniciais (precoce e intermediária) pode ser diagnosticada e revertida, porém, nos casos avançados (estágio grave), resta apenas o tratamento sintomático. A NAC está associada a um maior índice de morbidade e mortalidade cardiovasculares e pior qualidade de vida nos indivíduos diabéticos

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.

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.