Hypoglycemia post bariatric surgery: drugs with different mechanisms of action to treat a unique disorder

ABSTRACT Postprandial hypoglycemia (PPH) is a complex and multifactorial complication of bariatric surgery (BS). PPH may cause severe symptoms or be asymptomatic. The treatment of this condition requires dietary changes, but severe cases require drug therapy. The number of therapeutic options is limited and are often associated with adverse side effects. Different classes of drugs have been used and tested, but the resolution of PPH remains a challenge for physicians and patients. In this review, we gathered articles on PPH after BS from PubMed searches (2001 to 2022) and focused on the main drugs tested for the treatment of this condition, such as acarbose, somatostatin analogues, type 2 sodium-glucose cotransporter inhibitors, calcium channel blockers, and liraglutide. Avexitide and glucagon pump are two new therapeutic options that have been recently tested. For the search, the terms "postbariatric hypoglycemia," "bariatric surgery," and "late dumping syndrome" were used. PPH after BS is a frequent condition that should always be evaluated after BS. Treatment should be individualized and the available therapeutic options may be useful based on the condition's pathophysiology.

Hypoglycemia post bariatric surgery: drugs with different mechanisms of action to treat a unique disorder.

Postprandial hypoglycemia (PPH) is a complex and multifactorial complication of bariatric surgery (BS). PPH may cause severe symptoms or be asymptomatic. The treatment of this condition requires dietary changes, but severe cases require drug therapy. The number of therapeutic options is limited and are often associated with adverse side effects. Different classes of drugs have been used and tested, but the resolution of PPH remains a challenge for physicians and patients. In this review, we gathered articles on PPH after BS from PubMed searches (2001 to 2022) and focused on the main drugs tested for the treatment of this condition, such as acarbose, somatostatin analogues, type 2 sodium-glucose cotransporter inhibitors, calcium channel blockers, and liraglutide. Avexitide and glucagon pump are two new therapeutic options that have been recently tested. For the search, the terms "postbariatric hypoglycemia," "bariatric surgery," and "late dumping syndrome" were used. PPH after BS is a frequent condition that should always be evaluated after BS. Treatment should be individualized and the available therapeutic options may be useful based on the condition's pathophysiology.

SGLT2 Inhibition with Empagliflozin as a Possible Therapeutic Option for Postprandial Hypoglycemia After Bariatric Surgery.

PURPOSE: Since SGLT2 inhibitors may reduce postprandial hyperglycemia, this study aimed to evaluated whether empagliflozin might be useful in the treatment of postprandial hypoglycemia (PPH) postbariatric surgery (BS). PATIENTS AND METHODS: Fourteen patients who underwent BS, nine without type 2 diabetes and five with diabetes before surgery and in remission after surgery, were included. Seven of them presented symptoms of PPH (hypoglycemic group; HG) and seven were asymptomatic (nonhypoglycemic group (NHG)). A meal tolerance test was performed before and after administration of a daily dose of empagliflozin (EMPA) 25 mg for 3 days. Plasma glucose and serum insulin levels were measured. RESULTS: In HG, compared with NHG, in the basal test, the area under the curve (AUC) of plasma glucose levels (AUCgly) was smaller (158.3 ± 25.3 vs 276.6 ± 79.2 mg h dL-1; p = 0.001) while the AUC of insulin levels (AUCins) did not differ, leading to a higher AUCins/AUCgly ratio (0.79 ± 0.46 vs 0.38 ± 0.20; p = 0.055) and a lower HOMA-IR (0.92 ± 0.22 vs 1.75 ± 0.77; p = 0.030). The HG after EMPA, but not the NHG, showed significant increases in glycemia leading to greater AUCgly (158.0 ± 25.3 to 197.2 ± 51.6 mg h dL-1; p = 0.043) without significant changes in AUCins. HOMA-IR increased only in the HG (0.92 ± 0.20 vs 1.61 ± 0.30; p = 0.025) and, when both groups were analyzed together, both before and post EMPA, a significant correlation was found between HOMA-IR and AUCgly values (r = 0.594; p = 0.002). CONCLUSION: Our results suggest that empagliflozin increased glycemic levels in patients with PPH possibly through increases in hepatic glucose production.

Associations between binge eating, depressive symptoms and anxiety and weight regain after Roux-en-Y gastric bypass surgery.

BACKGROUND: Weight regain (WR) after bariatric surgery (BS) is frequent. OBJECTIVE: The aim of this study was to evaluate whether the occurrence of psychiatric disorders would be associated with short- and long-term WR after BS. METHODS: Ninety-six patients (77.6% female, age 40.2 ± 10.1 years, BMI of 50 ± 8.2 kg/m2) from the Obesity and Bariatric Surgery Outpatient Clinic of the Universidade Federal São Paulo completed the Questionnaire on Eating and Weight Patterns-Revised, the Beck Depression Inventory and an anxiety inventory to assess the occurrence of binge eating, depressive symptoms (DS) and anxious symptoms (AS) before and after short-term and long-term BS. RESULTS: Twenty-four months after BS, the prevalence of binge eating, depression and anxiety decreased from 100 to 13%, 100 to 15% and 43 to 4%, respectively. The mean WR of 35.2 ± 17.3% of weight loss occurred in nine patients after 24 months and was associated with binge eating (p = 0.002) but not with DS or AS. At long-term follow-up (12 ± 1.5 years), 67% had a mean WR of 50.3 ± 24.9%. The prevalence of binge eating, DS and AS were 48%, 46% and 63%, respectively, in this group, and significant associations were observed between WR and binge eating (p = 0.001), DS (p = 0.029) and AS (p = 0.001). Furthermore, the number of psychiatric disorders was inversely associated with the percentage of weight loss (p < 0.05) and positively associated with WR (p < 0.05). CONCLUSION: Weight regain was associated with the occurrence of binge eating in the short and long term after BS, whereas the occurrence of depressive and anxious symptoms was associated with WR only in the long term. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Muscle Echogenicity and Changes Related to Age and Body Mass Index.

INTRODUCTION: Muscle fibers are lost and replaced by fat- and fibrous-tissue infiltration during aging. This process decreases muscle quality and influences tissue appearance on ultrasound images over time. Increased muscle "echogenicity" represents changes caused by fat- and fibrous-tissue infiltration and can be quantified with recently developed software. OBJECTIVE: To investigate skeletal muscle quality through echogenicity, estimates according to participant's body mass index (BMI) and age were taken. METHODS: This was a cross-sectional study performed at the Pennington Biomedical Research Center, Baton Rouge, Louisiana with 117 participants (57 men and 60 women), with mean age (±SD) 38.9 ± 17.0 years and BMI 28.6 ± 6.2 kg/m². All participants were examined by ultrasound (LOGIQ GE Healthcare), using a 5.0-MHz linear transducer. Participants had muscle thickness measured by ultrasound at 4 anatomic locations (biceps and triceps brachial, femoral quadriceps, and calf triceps). Echogenicity was analyzed with specific software (Pixel Health) that evaluated the image in gray scale. RESULTS: According to BMI, 41% of participants were obese. There was a positive correlation between age and thigh-muscle echogenicity (rp = 0.534, P < .0001) and a negative correlation between thigh-muscle echogenicity and thickness (rp = -0.395, P <.0001). There was high muscle echogenicity in participants with overweight and obesity aged 50 years or older (P < .05). CONCLUSION: Older age and higher BMI were associated with stronger echogenicity signals and smaller muscle thickness. People with overweight, obesity, and/or older than 50 years old have reduced muscle quality with smaller muscle thickness, as observed with ultrasound.

Influence of Menopausal Hormone Therapy on Body Composition and Metabolic Parameters.

The loss of estrogen with menopause is associated with an increase in central fat. The objective of this study was to evaluate the effects of menopause hormone therapy (HT) on body composition and metabolic parameters in postmenopausal women. A prospective study was conducted among postmenopausal women from the Climacteric clinic, Universidade Federal de São Paulo. Thirty-two participants, median age 51 years, were included. Sixteen women were eligible to receive a low-dose continuous combined HT, containing 1 mg of E2 plus 0.125 mg of trimegestone for 6 months. The other 16 women remained in the control group. In the HT group, significant decreases from baseline were evident for the total cholesterol (TC) (p < 0.05) and LDL levels (p < 0.05). The HDL significantly decreased (p < 0.05). However, the TC/HDL ratio also decreased (p = 0.05). The parameters of body composition, after 6 months of HT, were maintained. In the control group, body mass index levels increased from baseline, however, with nonstatistically significant differences (p = 0.06). Analyzing the body composition showed a significant increase in the trunk body fat (p = 0.04), trunk region fat (p = 0.04), and total region fat (p = 0.03) after 6 months. In conclusion, the present study provides evidence that HT can stunt the increase in total body fat and prevent the shift from a more central fat distribution observed in early postmenopausal period.

Binge eating disorder is not predictive of alcohol abuse disorders in long-term follow-up period after Roux-en-Y gastric bypass surgery.

INTRODUCTION: Some studies have shown an increase in alcohol use disorders (AUD) after Roux-en-Y gastric bypass surgery (RYGB), but its relationship with binge eating disorder (BED) has not been fully explored. The purpose of this study was to determine the prevalence of AUD and BED after RYGB and also to evaluate if BED is predictive of late postoperative occurrence of AUD or BED. METHODS: Patients (n = 46) submitted to RYGB, in a tertiary outpatient weight management service at a Federal University of Sao Paulo, Brazil, were tested for BED and AUD using the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) and AUDIT, respectively. BED was tested before surgery, while both disorders were evaluated with a follow-up period of 12 ± 1.6 years after RYGB. RESULTS: No patients reported AUD before RYBP. After a mean period of 12 years from surgery, ten patients (21.7%) were diagnosed with AUD. Before surgery, BED was present in 24 patients (52.2%) and it was detected in seven out of these 24 patients (29.2%) after RYGB. Thirteen new cases of BED (28.2%) were detected after surgery; total of 20 patients (43.5%) with BED. No association was found between pre- and postsurgery BED (p = 0.148). After RYGB, four out of 24 patients (16.6%) with presurgery BED developed AUD, and no association was found between presurgery BED and postsurgery AUD (p = 0.384). Seven out of ten patients (70%) with AUD after RYGB also developed BED, but no statistical significance was found between these two disorders (p = 0.061). CONCLUSION: The presence of BED before RYGB did not predict AUD and BED after RYGB. Nevertheless, factors involved in a possible association between BED and AUD after surgery remain to be determined. LEVEL OF EVIDENCE: Level III, cohort study.

Sleep disorders in polycystic ovary syndrome: influence of obesity and hyperandrogenism.

OBJECTIVE: This study aims to evaluate the sleep of subjects with polycystic ovary syndrome (PCOS), with and without hyperandrogenism, in comparison with a healthy control group and examine the effects of hyperandrogenism and obesity on sleep parameters. METHODS: A total of 44 volunteers were recruited to participate in the study. Clinical, biochemical and polysomnographic parameters were used to diagnose PCOS and hyperandrogenism. The evaluation of sleep quality was made using validated questionnaires and polysomnography test. The frequency of obstructive sleep apnea was also compared between the groups. RESULTS: The study revealed that women with PCOS presented poorer subjective sleep quality, increased incidence of snoring and a higher risk of obstructive sleep apnea, based on the Berlin questionnaire. Also, after adjusting for body mass index, PCOS subjects had rapid eye movement (REM) time lower than those in the control group. PCOS women versus those without hyperandrogenism did not differ on any sleep measurement. Women with obstructive sleep apnea were only diagnosed in the PCOS group. CONCLUSIONS: Our results indicate that PCOS impairs subjective sleep quality, as well as objective sleep quality, due to a reduction in REM sleep stage time in women diagnosed with the syndrome. Obesity affected sleep-related parameters but hyperandrogenism had no effect. Only the PCOS group had obstructive sleep apnea diagnosis.

Sleep disorders in polycystic ovary syndrome: influence of obesity and hyperandrogenism

SUMMARY OBJECTIVE: This study aims to evaluate the sleep of subjects with polycystic ovary syndrome (PCOS), with and without hyperandrogenism, in comparison with a healthy control group and examine the effects of hyperandrogenism and obesity on sleep parameters. METHODS: A total of 44 volunteers were recruited to participate in the study. Clinical, biochemical and polysomnographic parameters were used to diagnose PCOS and hyperandrogenism. The evaluation of sleep quality was made using validated questionnaires and polysomnography test. The frequency of obstructive sleep apnea was also compared between the groups. RESULTS: The study revealed that women with PCOS presented poorer subjective sleep quality, increased incidence of snoring and a higher risk of obstructive sleep apnea, based on the Berlin questionnaire. Also, after adjusting for body mass index, PCOS subjects had rapid eye movement (REM) time lower than those in the control group. PCOS women versus those without hyperandrogenism did not differ on any sleep measurement. Women with obstructive sleep apnea were only diagnosed in the PCOS group. CONCLUSIONS: Our results indicate that PCOS impairs subjective sleep quality, as well as objective sleep quality, due to a reduction in REM sleep stage time in women diagnosed with the syndrome. Obesity affected sleep-related parameters but hyperandrogenism had no effect. Only the PCOS group had obstructive sleep apnea diagnosis.

RESUMO OBJETIVO: Este estudo objetivou avaliar o sono de mulheres com síndrome do ovário policístico, com e sem hiperandrogenismo, em comparação com um grupo controle saudável, e estudar os efeitos do hiperandrogenismo e da obesidade nos parâmetros do sono. MÉTODOS: Um total de 44 voluntárias foram recrutadas para participar do estudo. Os parâmetros clínicos, bioquímicos e polissonográficos e foram usados para diagnosticar SOP e hiperandrogenismo. A avaliação da qualidade de sono foi feita usando questionários validados e o exame polissonográfico. A frequência de síndrome da apneia obstrutiva também foi comparada entre os grupos. RESULTADOS: O estudo revelou que mulheres com SOP apresentaram menor qualidade de sono subjetiva, incidência aumentada de ronco e maior risco para síndrome da apneia obstrutiva, baseada no questionário de Berlin. Ademais, após o ajuste para índice de massa corpórea, mulheres com SOP tiveram menor tempo de sono REM do que aquelas do grupo controle. Dentre as mulheres com SOP, aquelas com hiperandrogenismo não tiveram diferenças em nenhuma variável do sono. Mulheres com síndrome da apneia obstrutiva foram diagnosticadas no grupo SOP. CONCLUSÕES: Nossos resultados indicam que a SOP afeta a qualidade subjetiva de sono, bem como a qualidade objetiva e do sono, em razão da redução do tempo de sono REM em mulheres diagnosticadas com a síndrome. A obesidade afetou parâmetros relacionados ao sono, mas o hiperandrogenismo não teve efeito. A síndrome da apneia obstrutiva somente foi diagnosticada em mulheres com SOP.

Association of endothelial dysfunction with cardiovascular risk factors and new-onset diabetes mellitus in patients with hypertension.

Asymmetric dimethylarginine (ADMA), which is the main endogenous inhibitor of nitric oxide synthase, plays a critical role in the process of endothelial dysfunction. The authors evaluated the association between high plasma ADMA levels in patients with hypertension and the presence of cardiovascular risk factors and the development of type 2 diabetes mellitus (DM) and cardiovascular outcomes, including death. The authors evaluated 191 patients with hypertension who were stratified into two groups according to the median value of basal ADMA: those with high levels of plasma ADMA (>0.55 µmol/L) and low levels of plasma ADMA (≤0.55 µmol/L) who were prospectively evaluated over 5.8 years. High ADMA levels were seen in patients with higher weight, body mass index, waist circumference, triglycerides, uric acid, and high-sensitivity C-reactive protein, and lower levels of high-density lipoprotein cholesterol and in patients with type 2 DM. There was an association between high plasma ADMA levels and the occurrence of cardiovascular death. In a subgroup of patients with hypertension free from metabolic syndrome and DM at baseline, there was an association between high ADMA levels and the development of type 2 DM. This study confirms the association of high plasma ADMA levels and the presence of cardiovascular risk factors in patients with hypertension and suggests a positive predictive value of high plasma ADMA levels for cardiovascular death in patients with hypertension and also for the development of type 2 DM in a subgroup of patients with hypertension free from metabolic abnormalities.

Relation of asymmetrical dimethylarginine levels with renal outcomes in hypertensive patients with and without type 2 diabetes mellitus.

AIM: The aim of the study was to evaluate the association between high plasma ADMA levels, a biomarker of endothelial dysfunction, with the progression of albuminuria and chronic kidney disease (CKD) in hypertensive patients, with and without type 2 diabetes mellitus. METHODS: We successfully contacted 213 of 644 patients who had been evaluated between 2004 and 2005 and for whom basal data were available. After the exclusion of 51 patients, 162 hypertensive patients who were free from albuminuria were stratified into the following 4 groups according to the presence of diabetes and plasma ADMA percentiles: general hypertensive patients with high levels of plasma ADMA (>P4 or ADMA > 0.61 µmol/L), general hypertensive patients with low levels of plasma ADMA (≤P4), diabetic hypertensive patients with high levels of plasma ADMA (>P4), and diabetic hypertensive patients with low levels of plasma ADMA (≤P4). RESULTS: The patients were prospectively evaluated over 5.8 years. High ADMA levels were associated with the progression of albuminuria in hypertensive patients, with and without type 2 diabetes. Major increases in the ADMA value during follow-up were associated with the progression of CKD, and direct correlations between ADMA changes and GFR changes were observed in the whole group and in the subgroup of diabetic patients. CONCLUSIONS: We suggest that high plasma ADMA levels might be a biomarker of renal disease progression and might even be an early predictor of albuminuria and its progression to the late stages of renal disease in hypertensive and diabetic hypertensive patients.

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

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.

Present Insights on Cardiomyopathy in Diabetic Patients.

The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.

The imbalance of sex-hormones related to depressive symptoms in obese men.

Obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Our objectives were to evaluate the relationship of sex-hormones profiles and frequency of depressive symptoms in 43 obese men, in a cross-sectional study. They had 19-60 years, and body mass index 30-50 kg/m(2). LH, total and free testosterone (TT and FT), estradiol (E2), sex hormone binding globulin, estradiol/total testosterone ratio (E2/T) were analyzed. Depressive symptoms were evaluated by "beck depression inventory" (BDI), and significant depression was considered if BDI ≥ 16.Thirty-four (80%) presented low TT levels, but only 4 (14%) had low free testosterone and hypogonadism symptoms; 12 of 43 (28%) presented increased E2. Forty five (56%) presented depressive symptoms, but 16 (28% of the 45) had significant depression. BDI correlated positively with E2 (r = 0.407; p = 0.001) and E2/T (r = 0.473; p = 0.001), but not TT or FT. Patients with significant depressive showed higher levels of estradiol (136 ± 48 versus 103 ± 48 pg/ml, p = 0.02) and E2/T (16.0 ± 9.9 versus 9.8 ± 4.6; p = 0.002) (mean ± SD).In conclusion, obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had our patients.

Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes.

OBJECTIVE: To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in people with type 2 diabetes. METHODS: A retrospective consecutive case series of 95 patients with type 2 diabetes and DME who were treated with anti-VEGF therapy. We examined 2 cohorts: patients taking only oral antidiabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity and change in central subfield macular thickness measured by spectral-domain optical coherence tomography. The additional variables analyzed included glycated hemoglobin (A1C), creatinine, blood pressure and body mass index and their correlations with clinical findings. RESULTS: Both groups had a statistically significant improvement in visual acuity (oral antidiabetic agents group: 20/61 to 20/49, p=0.003; insulin therapy group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12-month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, central subfield macular thickness also improved significantly in both groups: from 454.7 µm to 354.9 µm (p<0.001) in the oral antidiabetic agents group and from 471.5 µm to 368.4 µm (p<0.001) in the insulin therapy group. Again, there was no significant difference between groups at initial or 12-month follow-up examinations (p=0.586 and p=0.591, respectively). Mean A1C levels remained relatively stable during the follow up in both groups. CONCLUSION: Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared with oral antidiabetic agents, does not modify the anatomic or functional effectiveness of DME treatment.

Adrenocortical production is associated with higher levels of luteinizing hormone in nonobese women with polycystic ovary syndrome.

Objective. Insulin resistance (IR) and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS). The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese) and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX) 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH) levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r = -0.52; P = 0.001) and insulin (r = -0.47; P = 0.003) and positive correlation with LH (r = 0.40; P = 0.016). Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

Diabetes guidelines may delay timely adjustments during treatment and might contribute to clinical inertia.

Clinical inertia and poor knowledge by many physicians play an important role in delaying diabetes control. Among other guidelines, the Position Statement of the American Diabetes Association/European Association for the Study of Diabetes on Management of Hyperglycemia in Type 2 Diabetes is a respected guideline with high impact on this subject in terms of influencing physicians in the definition of strategic approach to overcome poor glycemic control. But, on the other hand, it carries a recommendation that might contribute to clinical inertia because it can delay the needed implementation of more vigorous, intensive, and effective strategies to overcome poor glycemic control within a reasonable time frame during the evolution of the disease. The same is true with other respected algorithms from different diabetes associations. Together with pharmacological interventions, diabetes education and more intensive blood glucose monitoring in the initial phases after the diagnosis are key strategies for the effective control of diabetes. The main reason why a faster glycemic control should be implemented in an effective and safe way is to boost the confidence and the compliance of the patient to the recommendations of the diabetes care team. Better and faster results in glycemic control can only be safely achieved with educational strategies, structured self-monitoring of blood glucose, and adequate pharmacological therapy in the majority of cases.

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema.

AIMS: Evaluate the role of systemic factors on the functional and anatomic outcomes of anti-VEGF therapy for diabetic macular edema (DME). METHODS: A retrospective consecutive case series of 124 patients with DME treated with anti-VEGF therapy was collected. The main outcome measures were change in best corrected visual acuity (BCVA) and change central subfield macular thickness (CST) measured with spectral-domain ocular tomography coherence (SD-OCT); and their correlation with clinical findings. RESULTS: Patients with serum hemoglobin A1c values (HbA1c) ≤ 7.0% had a statistically significant improvement in BCVA (20/66 to 20/43, p < 0.001), and those patients with HBA1c > 7.0% also had a significant but less robust improvement in BCVA (20/78 to 20/62, p = 0.024). CST improved significantly in both groups, but showed a larger magnitude of improvement in the group with better DM control [-140.7 microns (p < 0.001) and -83.3 microns (p < 0.001)]. Mean HBA1c levels remained relatively stable during the follow-up in both groups, but patients with improved glucose control during the study duration had a significantly lower retinal thickness than patients that had a stable or worsening HbA1c (mean final CST of 324.3 versus 390.0 µm, respectively, p = 0.042). Other systemic parameters were not correlated with changes in OCT thickness or BCVA. There was not a significant difference related to number of intravitreal injection in the HbA1c ≤ 7.0% group compared to HbA1c > 7.0% group, mean of 5.48 and 6.0 intravitreal injections respectively (p = 0.362). CONCLUSION: This study suggests that glucose regulation can impact the response to anti-VEGF therapy in the management of DME.