Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Glucose control and psychosocial outcomes with use of automated insulin delivery for 12 to 96 weeks in type 1 diabetes: a meta-analysis of randomised controlled trials.

BACKGROUND: Glycaemic control of Type 1 Diabetes Mellitus (T1DM) remains a challenge due to hypoglycaemic episodes and the burden of insulin self-management. Advancements have been made with the development of automated insulin delivery (AID) devices, yet, previous reviews have only assessed the use of AID over days or weeks, and potential benefits with longer time of AID use in this population remain unclear. METHODS:  We performed a systematic review and meta-analysis of randomised controlled trials comparing AID (hybrid and fully closed-loop systems) to usual care (sensor augmented pumps, multiple daily insulin injections, continuous glucose monitoring and predictive low-glucose suspend) for adults and children with T1DM with a minimum duration of 3 months. We searched PubMed, Embase, Cochrane Central, and Clinicaltrials.gov for studies published up until April 4, 2023. Main outcomes included time in range 70-180 mg/dL as the primary outcome, and change in HbA1c (%, mmol/mol), glucose variability, and psychosocial impact (diabetes distress, treatment satisfaction and fear of hypoglycaemia) as secondary outcomes. Adverse events included diabetic ketoacidosis (DKA) and severe hypoglycaemia. Statistical analyses were conducted using mean differences and odds ratios. Sensitivity analyses were performed according to age, study duration and type of AID device. The protocol was registered in PROSPERO, CRD42022366710. RESULTS: We identified 25 comparisons from 22 studies (six crossover and 16 parallel designs) including a total of 2376 participants (721 in adult studies, 621 in paediatric studies, and 1034 in combined studies) which were eligible for analysis. Use of AID devices ranged from 12 to 96 weeks. Patients using AID had 10.87% higher time in range [95% CI 9.38 to 12.37; p < 0.0001, I2 = 87%) and 0.37% (4.77 mmol/mol) lower HbA1c (95% CI - 0.49% (- 6.39 mmol/mol) to - 0.26 (- 3.14 mmol/mol); p < 0·0001, I2 = 77%]. AID systems decreased night hypoglycaemia, time in hypoglycaemia and hyperglycaemia and improved patient distress, with no increase in the risk of DKA or severe hypoglycaemia. No difference was found regarding treatment satisfaction or fear of hypoglycaemia. Among children, there was no difference in glucose variability or time spent in hypoglycaemia between the use of AID systems or usual care. In sensitivity analyses, results remained consistent with the overall analysis favouring AID. CONCLUSION: The use of AID systems over 12 weeks, regardless of technical or clinical differences, improved glycaemic outcomes and diabetes distress without increasing the risk of adverse events in adults and children with T1DM.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity.

AIM: This study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents. METHODS: This study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR). RESULTS: The eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles. CONCLUSIONS: In a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.

Diabetes tipo 2 e transplante renal: estudo comparativo sobre adesão medicamentosa / Diabetes tipo 2 y trasplante renal: estudio comparativo sobre la adhesión farmacológica / Type 2 diabetes and kidney transplant: comparative study on medication adherence

Resumo Objetivo Investigar a adesão medicamentosa no Diabetes Mellitus tipo 2 entre transplantados renais e não transplantados. Métodos Estudo comparativo entre pacientes assistidos no Centro de Diabetes (Grupo 1 sem transplante renal) e no Ambulatório de Pós-Transplante Renal do Hospital do Rim e da Hipertensão (Grupo 2 com transplante renal), ambos na cidade de São Paulo. A amostra foi composta por maiores de 18 anos, com diagnóstico de diabete tipo 2 prévio e em uso de medicamentos para o controle glicêmico. A coleta de dados ocorreu de outubro de 2017 a outubro de 2018. Aplicou-se aos participantes: formulário sócio clínico, instrumento de Medida de Adesão ao Tratamento Medicamentoso no Diabetes Mellitus (antidiabéticos orais e insulina) e a escala de Ansiedade e Depressão. O projeto foi aprovado no Comitê de Ética e Pesquisa como 0712/2017. Resultados Amostra composta de 107 pacientes (Grupo 1: 56 e Grupo 2: 51), maior porcentagem de homens, média de idade de 63,3 anos, provenientes da região metropolitana de São Paulo, aposentados, casados, com sobrepeso, sem sintomas de ansiedade e depressão. Os pacientes autorreferiram ter adesão aos medicamentos para o controle do diabetes, porém os resultados da hemoglobina glicada variaram entre 8,3 e 8,7% entre os grupos, ambos acima de 7%. Conclusão Ao analisar a relação entre a adesão autorreferida, hemoglobina glicada, ansiedade e depressão não foi possível evidenciar correlação estatisticamente significante. Os parâmetros avaliados neste estudo não permitiram estabelecer a relação de causa e efeito.

Resumen Objetivo Investigar la adhesión farmacológica en la Diabetes mellitus tipo 2 en trasplantados renales y no trasplantados. Métodos Estudio comparativo entre pacientes atendidos en el Centro de Diabetes (Grupo 1 sin trasplante renal) y en los Consultorios Externos de Postrasplante Renal del Hospital del Riñón y de la Hipertensión (Grupo 2 con trasplante renal), ambos en la ciudad de São Paulo. La muestra fue formada por mayores de 18 años, con diagnóstico previo de diabetes tipo 2 y en uso de medicamentos para control glucémico. La recopilación de datos se realizó de octubre de 2017 a octubre de 2018. Se aplicaron los siguientes instrumentos a los participantes: formulario socio-clínico, instrumento de Medida de Adhesión al Tratamiento Farmacológico (antidiabéticos orales e insulina) y escala de Ansiedad y Depresión. El proyecto fue aprobado por el Comité de Ética e Investigación con el número 0712/2017. Resultados Muestra formada por 107 pacientes (Grupo 1: 56 y Grupo 2: 51), mayor porcentaje de hombres, promedio de edad 63,3 años, provenientes de la región metropolitana de São Paulo, jubilados, casados, con sobrepeso, sin síntomas de ansiedad y depresión. Los pacientes autodeclararon adherir a los medicamentos para el control de la diabetes, pero los resultados de la hemoglobina glicosilada variaron entre 8,3 y 8,7 % entre los grupos, más de 7 % en ambos. Conclusión Al analizar la relación entre la adhesión autodeclarada, la hemoglobina glicosilada, la ansiedad y la depresión, no se observó correlación estadísticamente significativa. Los parámetros evaluados en este estudio no permitieron establecer una relación de causa y efecto.

Abstract Objective To investigate medication adherence in type 2 Diabetes Mellitus among kidney transplant recipients and non-transplant recipients. Methods Comparative study between patients assisted at the Diabetes Center (Group 1 without kidney transplant) and at the Post-Renal Transplant Outpatient Clinic of the Hospital do Rim e da Hipertensão (Group 2 with kidney transplant), both in the city of São Paulo. The sample consisted of people over 18 years of age with a previous diagnosis of type 2 diabetes using medication for glycemic control. The data collection period was from October 2017 to October 2018. The following was applied to participants: socio-clinical form, instrument for Measuring Adherence to Medication Treatment in Diabetes Mellitus (oral antidiabetics and insulin) and the Anxiety and Depression scale. The project was approved by the Research Ethics Committee as 0712/2017. Results Sample composed of 107 patients (Group 1: 56 and Group 2: 51), higher percentage of men, mean age of 63.3 years, from the metropolitan region of São Paulo, retired, married, overweight, without symptoms of anxiety and depression. Even though patients self-reported adherence to medication for diabetes control, results of glycated hemoglobin ranged between 8.3 and 8.7% between groups, both above 7%. Conclusion When analyzing the relationship between self-reported adherence, glycated hemoglobin, anxiety and depression, a statistically significant correlation could not be found. The parameters evaluated in this study did not allow establishing a cause and effect relationship.

The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

Parents' cardiovascular risk factors are related to overweight and obesity in young Brazilians with type 1 diabetes.

AIM: To identify family background characteristics and cardiovascular disease (CVD) risk factors linked to overweight and obesity in Brazilian with type 1 diabetes (T1D). METHODS: We performed cross-sectional anthropometric and laboratory analyses in young individuals with T1D. RESULTS: Among 181 participants, 87 were women and 94 were men (64%/78% normal weight, 27%/15% overweight and 9%/7% obese). Obese men were older; were more likely to be Black; had higher triglyceride levels and diastolic blood pressure (BP), lower estimated glucose disposal rate (eGDR) and higher prevalence of first-degree relatives (FDR) with hypertension and early CVD. Overweight and obese women were more likely to have lower eGDR, and obese women were more likely to have FDR with obesity. CONCLUSION: One third of young people with T1D were overweight or obese. Excess weight was associated with family history (FH) of obesity for women and FH of early CVD or hypertension for men. BMI was related to decreased insulin sensitivity in both genders, but only men with T1D had metabolic impairment. Our data highlight the importance of considering family background in individuals with T1D.

The first series of cases of ketosis-prone type 2 diabetes (flatbush diabetes) in Brazilian adults.

Ketosis-prone type 2 diabetes (KPD) is an emerging form of diabetes mellitus characterized by unprovoked ketoacidosis, absence of autoimmunity and beta-cell dysfunction. The KPD may improve after initial glycemic compensation and evolve to exogenous insulin independence, most cases were observed in populations with African or Hispanic backgrounds. We reviewed the literature on KPD and, to date, only one case of KPD has been described in Brazil's multi-ethnic population. A group of adult Brazilian KPD patients without autoimmunity and insulinopenia was identified for this study. We report a retrospective study of four KPD cases (3 males) evaluated in southeast Brazil, the patients were overweight or obese, age between the third and fifth decades of life, had a family history of type 2 diabetes, hyperglycemia (809.5 ± 344.2 mg/dL), acidosis (pH 7.21 ± 0.07; normal range (nr): 7.35-7.45 and bicarbonate 9.1 ± 6.2; nr: 22-26 mEq/mL), ketonuria (142.5 ± 114.4 mg/dL; nr: absence), absence of glutamic acid decarboxylase antibodies (GAD-65), and beta-cell function reserve (C-peptide 1.19 ± 0.53 ng/mL - nr: 1.1-4.4 ng/mL) on diagnosis. After glycemic compensation, there was increase of C-peptide (2.21 ± 0.41) indicating the recovery of beta-cell function and the time to insulin independence was 7.7 ± 3.5 months. They evolved after the period of glucotoxicity with insulin withdrawal and could be treated with oral antidiabetic therapy. This is the first case series of KPD described in Brazil being characterized by ketoacidosis at diagnosis, absence of autoimmunity, recovery of beta-cell function and insulin independence.

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes.

AIMS: To investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. METHODS: Participants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). RESULTS: Ninety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. CONCLUSION: CAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study.

Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2 ± 1.3vs. 40.7 ± 0.6 years old, OR 1.04; P = 0.001) and pretransplant hyperglycaemia and BMI ≥ 25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P = 0.032 and 57.4% vs. 27.7%, OR 3.5; P < 0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P = 0.0001), acute rejection (P = 0.021), calcium channel blockers (P = 0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio ≥ 3.5 at 1 year (P = 0.01) and at 3 years (P = 0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P = 0.035), pretransplant BMI ≥ 25 kg/m2 (P = 0.0001), posttransplant transient hyperglycaemia (P = 0.0001), and TG/HDL ratio ≥ 3.5 at 3-year posttransplant (P = 0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.

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.

Retinal malperfusion in albuminuric Type 1 diabetes mellitus patients without clinical signs of diabetic retinopathy: a prospective pilot study.

BACKGROUND: To report fluorescein angiography findings in a group of albuminuric Type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy. METHODS: Fifteen albuminuric T1DM patients with normal/near normal estimated glomerular filtration rate without diabetic retinopathy underwent fluorescein angiography; presence of microaneurysms, vascular permeability changes and retinal malperfusion were evaluated. RESULTS: Fluorescein angiography revealed microaneurysms, blood-retinal barrier breakdown and retinal ischemia in 10 (67%) and 11 (73%); 8 (53%) and 9 (60%); 2 (13%) and 5 (33%) of patients at baseline and follow up, respectively. Follow up time averaged 24.6 months, minimum follow up time was 20 months. Patients who presented retinal malperfusion had higher HbA1C and lower estimated glomerular filtration rate. CONCLUSIONS: Most albuminuric T1DM patients with a normal fundus exam had angiographic signs of diabetic retinopathy, some presenting retinal malperfusion. Retinal changes may be found with more sensitive testing in these patients, especially with impaired estimated glomerular filtration rate, even if the fundus exam is normal, and fluorescein angiography should be considered. These findings point to a homogenous presentation of the diabetic microangiopathies.

Diretriz brasileira baseada em evidências sobre prevenção de doenças cardiovasculares em pacientes com diabetes: posicionamento da Sociedade Brasileira de Diabetes (SBD), da Sociedade Brasileira de Cardiologia (SBC) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) / Brazilian evidence-based guideline on cardiovascular disease prevention in patients with diabetes: positioning of the Brazilian Society of Diabetes (SBD), the Brazilian Society of Cardiology (SBC) and the Brazilian Society of Endocrinology and Metabology (SBEM)

Resumo Fundamentação: desde o primeiro posicionamento da Sociedade Brasileira de Diabetes (SBD) sobre diabetes e prevenção cardiovascular, em 2014,1 importantes estudos têm sido publicados na área de prevenção cardiovascular e tratamento do diabetes,2 os quais contribuíram para a evolução na prevenção primária e secundária nos pacientes com diabetes. Ferramentas de estratificação de risco mais precisas, novos fármacos hipolipemiantes e novos antidiabéticos com efeitos cardiovasculares e redução da mortalidade, são parte desta nova abordagem para os pacientes com diabetes. O reconhecimento de que o diabetes é uma doença heterogênea foi fundamental, sendo claramente demonstrado que nem todos os pacientes diabéticos pertencem a categorias de risco alto ou muito alto. Um porcentual elevado é composto por pacientes jovens, sem os fatores de risco clássicos, os quais podem ser classificados adequadamente em categorias de risco intermediário ou mesmo em baixo risco cardiovascular. O presente posicionamento revisa as melhores evidências atualmente disponíveis e propõe uma abordagem prática, baseada em risco, para o tratamento de pacientes com diabetes. Estruturação: perante este desafio e reconhecendo a natureza multifacetada da doença, a SBD uniu-se à Sociedade Brasileira de Cardiologia (SBC) e à Sociedade Brasileira de Endocrinologia e Metabolismo (SBEM), e formou um painel de especialistas, constituído por 28 cardiologistas e endocrinologistas, para revisar as melhores evidências disponíveis e elaborar uma diretriz contendo recomendações práticas para a estratificação de risco e prevenção da Doença Cardiovascular (DVC) no Diabetes Melito (DM). As principais inovações incluem: (1) considerações do impacto de novos hipolipemiantes e das novas medicações antidiabéticas no risco cardiovascular; (2) uma abordagem prática, baseada em fator de risco, para orientar o uso das estatinas, incluindo novas definições das metas da Lipoproteína de Baixa Densidade-colesterol (LDL-colesterol) e colesterol não Lipoproteína de Alta Densidade HDL; (3) uma abordagem baseada em evidências, para avaliar a isquemia miocárdica silenciosa (IMS) e a aterosclerose subclínica em pacientes com diabetes; (4) as abordagens mais atuais para o tratamento da hipertensão; e (5) recomendação de atualizações para o uso de terapia antiplaquetária. Esperamos que esta diretriz auxilie os médicos no cuidado dedicado aos pacientes com diabetes. Métodos: inicialmente, os membros do painel foram divididos em sete subcomitês para definirem os tópicos principais que necessitavam de uma posição atualizada das sociedades. Os membros do painel pesquisaram e buscaram no PubMed estudos clínicos randomizados e metanálises de estudos clínicos e estudos observacionais de boa qualidade, publicados entre 1997 e 2017, usando termos MeSH: [diabetes], [diabetes tipo 2], [doença cardiovascular], [estratificação de risco cardiovascular] [doença arterial coronária], [rastreamento], [isquemia silenciosa], [estatinas], [hipertensão], [ácido acetilsalicílico]. Estudos observacionais de baixa qualidade, metanálises com alta heterogeneidade e estudos transversais não foram incluídos, embora talvez tenham impactado no Nível de Evidência indicado. A opinião de especialistas foi usada quando os resultados das buscas não eram satisfatórios para um item específico. É importante salientar que este posicionamento não teve a intenção de incluir uma revisão sistemática rigorosa. Um manuscrito preliminar, destacando recomendações de graus e níveis de evidência (Quadro 1), foi esboçado. Este passo levou a várias discussões entre os membros dos subcomitês, que revisaram os achados e fizeram novas sugestões. O manuscrito foi, então, revisto pelo autor líder, encarregado da padronização do texto e da inclusão de pequenas alterações, sendo submetido à apreciação mais detalhada pelos membros dos comitês, buscando uma posição de consenso. Depois desta fase, o manuscrito foi enviado para a banca editorial e edição final, sendo encaminhado para publicação. Quadro 1 Graus de recomendações e níveis de evidências adotados nesta revisão Grau de recomendação Classe I A evidência é conclusiva ou, se não, existe consenso de que o procedimento ou tratamento é seguro e eficaz Classe II Há evidências contraditórias ou opiniões divergentes sobre segurança, eficácia, ou utilidade do tratamento ou procedimento Classe IIa As opiniões são favoráveis ao tratamento ou procedimento. A maioria dos especialistas aprova Classe IIb A eficácia é bem menos estabelecida, e as opiniões são divergentes Classe III Há evidências ou consenso de que o tratamento ou procedimento não é útil, eficaz, ou pode ser prejudicial Níveis de Evidência A Múltiplos estudos clínicos randomizados concordantes e bem elaborados ou metanálises robustas de estudos clínicos randomizados B Dados de metanálises menos robustas, um único estudo clínico randomizado ou estudos observacionais C Opinião dos especialistas

A Systematic Review of Treatment of Painful Diabetic Neuropathy by Pain Phenotype versus Treatment Based on Medical Comorbidities.

BACKGROUND: Painful diabetic neuropathy (PDN) is a serious, polymorphic, and prevalent complication of diabetes mellitus. Most PDN treatment guidelines recommend a selection of drugs based on patient comorbidities. Despite the large numbers of medications available, most randomized clinical trials (RCTs) conducted so far have yielded unsatisfactory outcomes. Therefore, treatment may require a personalized approach based on pain phenotype or comorbidities. METHODS: To evaluate whether or not a patient's pain phenotype or comorbidities can influence the response to a specific PDN treatment, we conducted a systematic review using two different approaches: pain phenotype and associated comorbidities-based treatment. RESULTS: Out of 45 identified papers, 7 were thoroughly reviewed. We found four RCTs stratified according to pain phenotype with three main results: (1) paroxysmal pain had a better response to pregabalin; (2) the preservation of thermal sensation or nociception anticipated a positive response to the topical treatment of pain; and, (3) after a failure to duloxetine (60 mg/day), the patients with evoked pain or severe deep pain had a better response to association of duloxetine/pregabalin while those with paresthesia/dysesthesia benefited from duloxetine monotherapy (120 mg/day). By contrast, the other three papers provided weak and even contradictory evidence about PDN treatment based on comorbidities. CONCLUSION: Although more studies are needed to provide an adequate recommendation for clinical practice, our systematic review has provided some evidence that PDN phenotyping may optimize clinical outcomes and could, in the future, lead to both less empirical medicine and more personalized pain therapeutics.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

BACKGROUND: Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. MAIN BODY: The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. CONCLUSIONS: Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM)

BACKGROUND: Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. MAIN BODY: The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy.

Seborrheic keratoses and severe hypoinsulinemic hypoglycemia associated with insulin grow factor 2 secretion by a malignant solitary fibrous tumor.

A rare sign of some malignant tumors is a sudden eruption of multiple seborrheic keratoses called Leser-Trélat sign. Overproduction of insulin-like growth factor-2 (IGF2) or its precursor is the main mechanism related to non-islet cell tumor hypoglycemia. Doege-Potter syndrome is the name given to paraneoplastic hypoinsulinemic hypoglycemia in presence of a solitary fibrous tumor. This report describes a case of a patient with hypoinsulinemic hypoglycemia and Leser-Trélat sign associated with a malignant solitary fibrous tumor with IGF2 secretion. Both conditions have improved after tumor excision.

Cardiovascular autonomic neuropathy contributes to sleep apnea in young and lean type 1 diabetes mellitus patients.

Knowledge about association between sleep apnea and cardiovascular autonomic neuropathy (CAN) in type 1 diabetes mellitus (T1DM) might give some insight into the pathogenesis of this condition in these patients. In obese patients, excessive central adiposity, including a large neck circumference, can contribute to obstructive sleep apnea (OSA). Its presence in non-obese patients, however, indicates that it could be correlated with autonomic neuropathy. The aim of this study was to compare the prevalence of OSA in young and lean T1DM patients with and without CAN. We studied 20 adult, non-obese, T1DM patients who were divided into two groups according to the results of the cardiovascular autonomic reflex tests (CARTs). These two groups (9 with CAN and 11 without CAN) were compared to a control group of 22 healthy individuals, who were matched by age and BMI. A polysomnography was performed and sleep was analyzed. The CAN+ group had a significantly higher prevalence of sleep apnea compared to the other groups (67% CAN+; 23% CAN-; 4.5% controls: CAN+ vs. Control; p = 0.006 and CAN+ vs. CAN-; p = 0.02). The CAN- group had higher sleep efficiency compared to the CAN+ group, demonstrating impaired sleep architecture in diabetics with this chronic complication. In conclusion, OSA may be related to the presence of CAN in young and lean T1DM patients. It could contribute to worse the prognosis and reducing the quality of life of these patients without specific treatment of these conditions.