Joäo Roberto de Sá

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce

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.

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.

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/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% 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.

Latent Autoimmune Diabetes of the Adult (LADA) in a Brazilian Indian

CONTEXT Latent autoimmune diabetes of the adult (LADA) as originally described represents perhaps as many as 10 - 20% of adult-onset patients with diabetes. DESIGN case report. CASE REPORT A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA) is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD) characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.

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)

BackgroundSince 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 bodyThe 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.ConclusionsDiabetes 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.

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.

Doença arterial coronariana subclínica em pacientes com Diabetes Mellitus tipo 1 em hemodiálise

BACKGROUND In patients with type 1 diabetes mellitus, atherosclerosis occurs earlier in life and coronary artery disease (CAD) constitutes the major cause of death. OBJECTIVE Evaluate the prevalence and anatomic characteristics of coronary artery disease (CAD) in type 1 diabetic patients with chronic renal failure undergoing hemodialysis. METHODS This is a descriptive study of 20 patients with type 1 diabetes mellitus undergoing hemodialysis without known CAD. CAD was assessed by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). QCA was performed in all lesions >30%, visually. All proximal 18-mm segments of the coronary arteries were analyzed by IVUS. All other coronary segments with stenosis >30% were also analyzed. RESULTS Angiography detected 29 lesions >30% in 15 patients (75%). Eleven (55%) of the lesions were >50% and 10 (50%) >70%. Thirteen patients had all 3 major arteries interrogated by IVUS. Atherosclerosis was present in all patients and in all 51 proximal 18-mm segments analyzed. The mean vessel diameter of these segments was significantly larger at the IVUS than at the QCA, for all vessels. IVUS images of 25 (86.2%) of the 29 lesions >30% were obtained. Fibrotic plaques were common (48%) and 60% had intermediate vessel remodeling. CONCLUSION CAD was present in all vessels of all type 1 diabetic patients undergoing hemodialysis. These findings are in agreement with other autopsy, angiography and IVUS studies. Additionally, they indicate the need for additional epidemiological and imaging studies to better understand and treat such a complex and serious clinical condition affecting young people.

Hypertension and Diabetes

SummaryThe choice of an appropriate antihypertensive agent and the hazards of postural hypotension are common problems faced in the treatment of diabetic hypertensive patients. The results of 3 studies addressing these problems are described in this report. In the first study, indoramin, an α-blocking agent, was administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension. Blood pressure control was achieved in 57% of patients with mild, and in none with moderate hypertension. The blood glucose and insulin responses to an oral 50g glucose loading, as well as the blood concentrations of HbA1 did not change during therapy. Seven patients were excluded because of side effects. In 4 of them postural hypotension was observed.In the second study, the effects of angiotensin-converting enzyme (ACE) inhibitors, administered to patients with non-insulin-dependent diabetes and mild to moderate hypertension, were evaluated. Blood pressure control was achieved in 78% of the patients on captopril ( n=14 ) and in 74% of patients on enalapril therapy ( n=23). Symptomatic postural hypotension (n=2) and hyperkalaemia n=2 were observed with both drugs. Significant reductions in 24-hour urinary protein or albumin excretion were detected in 12 patients on enalapril therapy. No changes in 2-hour postprandial blood glucose and HbA1 levels were observed during therapy with ACE inhibitors. In the third study, dopaminergic antagonist agents were evaluated in diabetic patients with orthostatic hypotension. In 7 patients metoclopramide (20mg intravenously) reduced the fall in mean arterial pressure induced by upright tilt. This response was associated with increases in total peripheral resistance and no changes in cardiac output. In addition, domperidone, a peripheral dopaminergic antagonist, was given to 9 diabetic patients with orthostatic hypotension. Marked increases in upright systolic and diastolic blood pressure were detected after a period ranging from 10 to 30 days, and maintained in 6 patients who completed 1 year of therapy.Our results indicate that α-blockers may be a good therapeutic option for diabetic patients with mild hypertension. ACE inhibitiors are effective antihypertensive agents in diabetic patients but should be used with caution in those with renal failure or autonomic neuropathy. Dopaminergic antagonists appear to be effective in the treatment of diabetic orthostatic hypotension.

Microalbuminuria is associated with increased choroidal thickness in type 1 diabetes mellitus patients without diabetic retinopathy

pattern was observed for CPFT. SCT decreased from 245 57 lm at treatment start and remained decreased throughout the follow-ups. On average, 7.6 3.4 injections were given per eye. Only seven eyes (24%) needed additional PDT. No major adverse events, retinal detachment or endophthalmitis were observed. A Kaplan–Meier analysis showed that eyes in need of retreatment were 88% after 12 months and 59% after 24 months (Fig. 1). This is one of few studies to report treatment results of PCV in Caucasians and the first study to report results of aflibercept treatment beyond the first year. We ran the analyses separately for the treatment-na€ıve, which did not change the direction of the results or the conclusions. Overall, we found a short-term improvement in the BCVA, which on long term was more of a stabilization. Unlike in our Caucasian patients, lesions are more often located macular in Asians, which may explain why Asians present with a worse baseline BCVA but also experience a better treatment response (Kikushima et al. 2017; Lee et al. 2017). Hence, the relative worse response in terms of BCVA improvement in our Caucasian patients is likely a question of more peripherally located lesions that remains relatively unaffected by anatomical improvements from the treatment.