Lana Catani Ferreira Pinto

Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis

BACKGROUND Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. PURPOSE To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. STUDY SELECTION Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. DATA EXTRACTION Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia. DATA SYNTHESIS Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. LIMITATIONS Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. CONCLUSION There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patients clinical characteristics. PRIMARY FUNDING SOURCE Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacăo de Aperfeicoamento de Pessoal de Nível Superior.

Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies

Background: Thyroid nodules are a common finding in the general population, and their detection is increasing with the widespread use of ultrasound (US). Thyroid cancer is found in 5–15% of cases depending on sex, age, and exposure to other risk factors. Some US parameters have been associated with increased risk of malignancy. However, no characteristic seems sufficiently reliable in isolation to diagnose malignancy. The objective of this meta-analysis was to evaluate the diagnostic performance of US features for thyroid malignancy in patients with unselected thyroid nodules and nodules with indeterminate fine-needle aspiration (FNA) cytology. Methods: Electronic databases were reviewed for studies published prior to July 2012 that evaluated US features of thyroid nodules and reported postoperative histopathologic diagnosis. A manual search of references of review and key articles, and previous meta-analyses was also performed. A separate meta-analysis was performed including only nodules with indeterminate cytology. Analyzed features were solid structure, hypoechogenicity, irregular margins, absence of halo, microcalcifications, central vascularization, solitary nodule, heterogeneity, taller than wide shape, and absence of elasticity. Results: Fifty-two observational studies (12,786 nodules) were included. Nine studies included nodules with indeterminate cytology as a separate category, comprising 1851 nodules. In unselected nodules, all US features were significantly associated with malignancy with an odds ratio varying from 1.78 to 35.7, and microcalcifications, irregular margins, and a taller than wide shape had high specificities (Sp; 87.8%, 83.1%, 96.6%) and positive likelihood ratios (LHR; 3.26, 2.99, 8.07). Absence of elasticity was the single feature with the best diagnostic performance (sensitivity 87.9%, Sp 86.2%, and positive LHR 6.39). The presence of central vascularization was the most specific US feature in nodules with indeterminate cytology (Sp 96% and positive LHR 2.13). Conclusions: US features in isolation do not provide reliable information to select nodules that should have a FNA performed. A combination of US characteristics with higher likelihood ratios and consequently with higher post-test probabilities of malignancy—microcalcifications, or a taller than wide shape, or irregular margins, or absence of elasticity—will probably identify nodules with an increased risk for malignancy. Further studies are required to standardize elastography techniques and evaluate outcomes, especially in nodules with an indeterminate cytology.

Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]−6.12 to −4.56) of additional weight as compared with placebo. According to meta‐regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96–200 mg day−1, the weight loss was higher in trials with >28 weeks of duration (−6.58 kg [95%CI −7.48 to −5.68]) than in trials with ≤28 weeks (−4.11 kg [95%CI −4.92 to −3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64–2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered.

The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials

Background Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results. Methods and Findings Electronic databases were reviewed from 1946 (Embase) or 1966 (MEDLINE) up to 31 December 2014. Randomized clinical trials (RCTs) of at least 52 wk in duration evaluating second- or third-generation sulfonylureas in the treatment of adults with type 2 diabetes and reporting outcomes of interest were included. Primary outcomes were all-cause and cardiovascular mortality. Additionally, myocardial infarction and stroke events were evaluated. Data were summarized with Peto odds ratios (ORs), and the reliability of the results was evaluated with TSA. Forty-seven RCTs with 37,650 patients and 890 deaths in total were included. Sulfonylureas were not associated with all-cause (OR 1.12 [95% CI 0.96 to 1.30]) or cardiovascular mortality (OR 1.12 [95% CI 0.87 to 1.42]). Sulfonylureas were also not associated with increased risk of myocardial infarction (OR 0.92 [95% CI 0.76 to 1.12]) or stroke (OR 1.16 [95% CI 0.81 to 1.66]). TSA could discard an absolute difference of 0.5% between the treatments, which was considered the minimal clinically significant difference. The major limitation of this review was the inclusion of studies not designed to evaluate safety outcomes. Conclusions Sulfonylureas are not associated with increased risk for all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. Current evidence supports the safety of sulfonylureas; an absolute risk of 0.5% could be firmly discarded. Review registration PROSPERO CRD42014004330

Blood pressure means rather than nocturnal dipping pattern are related to complications in Type 2 diabetic patients

Aim  To determine whether systolic and diastolic blood pressure (BP) means, during ambulatory BP monitoring (ABPM), are more strongly correlated with microvascular complications and echocardiographic structural alterations than night‐time/daytime (N/D) BP ratio.

Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and meta-analysis

BackgroundNitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and physiologically critical steps of nephron function. Endothelial NOS (eNOS) gene has been considered a potential candidate gene to diabetic nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3) polymorphisms have been associated with DN, however some studies do not confirm this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used in this report. Case–control studies that had diabetic patients with DN as cases and diabetic patients without nephropathy as controls, as well as that evaluated at least one of the three polymorphisms of interest were considered eligible. All studies published up until December 31st, 2012 were identified by searching electronic databases. Hardy-Weinberg equilibrium assessment was performed. Gene-disease association was measured using odds ratio estimation based on the following genetic contrast/models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model.ResultsTwenty-two studies were eligible for meta-analysis (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a polymorphism, an association with DN was observed for all genetic models: allele contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28); recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with the exception for co-dominance model. As well, T-786C polymorphism showed association with all models, with exception for co-dominance model: allele contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97), recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23). For the G894T polymorphism, an association with DN was observed in allelic contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04-1.37).ConclusionsIn the present study, there was association of DN with eNOS 4b/a and T-786C polymorphism, which held in all genetic models tested, except for co-dominance model. G894T polymorphism was associated with DN only in allele contrast and in co-dominance model. This data suggested that the eNOS gene could play a role in the development of DN.

Which patients with diabetes should undergo ambulatory blood pressure monitoring

Objective To estimate the daytime ambulatory blood pressure monitoring (ABPM) value corresponding to the target office blood pressure (BP; 130/80 mmHg) for diabetic patients and to identify which patients with diabetes may benefit from ABPM. Methods A cross-sectional study was conducted with type 1 and type 2 diabetic patients. ABPM (Spacelabs90207) and office BP were measured. Target ABPM was estimated by linear regression equation using daytime ABPM and office BP. Office BP values corresponding to ABPM hypertension were determined by receiver operating characteristic curves. Results A total of 554 patients (type 1: n = 200, 36 ± 11 years, diabetes duration 17 ± 9 years; type 2: n = 354; 57 ± 9 years, diabetes duration 10 ± 7 years) were evaluated. Regression equations for SBP and DBP were ABPM = 64.3 + (0.50 office BP) and ABPM = 45.4 + (0.42 office BP), respectively. Daytime ABPM corresponding to the target office BP was 129.3/79 mmHg. Office BP less than 120 for systolic and less than 70 mmHg for diastolic had 90% sensitivity to rule out hypertension diagnosed by ABPM; office BP at least 145 for systolic or at least 90 mmHg for diastolic had 90% specificity to confirm ABPM hypertension. Within these values, 38% of patients were misclassified if only office values were considered. Conclusion In type 1 and type 2 diabetes, the recommended upper limit of daytime ABPM is 130/80 mmHg. Patients with office BP at least 120 for systolic or at least 70 for diastolic and less than 145 for systolic and less than 90 mmHg for diastolic should undergo ABPM to correctly determine their BP status.

Risk factors for micro and macrovascular disease in black and white patients with type 2 Diabetes mellitus

BACKGROUND The prevalence of chronic complications in type 2 diabetes mellitus (DM) is higher in black patients. The reason for this finding is still unknown. The objective of this study was to analyze the micro and macrovascular risk factor profile of type 2 DM patients without advanced diabetic nephropathy according to ethnicity. METHODS A cross-sectional multicentric regional study was conducted evaluating 780 patients. All patients were submitted to clinical and laboratory evaluation. Ethnicity was self-reported as white (n = 585) or black (n = 195). RESULTS Black patients had lower triglycerides [115 (35-892) vs. 152 (34-1236) mg/dl; P <0.001] and higher HDL-cholesterol levels than whites (48.3 +/- 13.5 vs. 44.8 +/- 12.1 mg/dl; P = 0.002).White and black patients did not differ regarding fasting plasma glucose, A1c test, total and LDL cholesterol, blood pressure levels, insulin and HOMA-IR. There were no differences between groups regarding medication in use (statin: 18.5 vs. 19.3%, P = 1.000; fibrates: 1.5 vs. 0.7%, P = 0.680; angiotensin converting enzyme inhibitors: 39.5 vs. 43.8%, P = 0.375; acetylsalicylic acid: 29.9 vs. 27.7%, P = 0.673). CONCLUSIONS There were no differences in the prevalence of the classic micro and macrovascular risk factors between ethnic groups. The study of non-conventional risk factors and genetic factors is essential to understand determinants of the worst outcomes presented by the African-Brazilian population.

Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and meta-analysis

Background Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a novel antidiabetic class that inhibits glucose reabsorption and produce glycosuria. These medications are being increasingly used as dual therapy with metformin for type 2 diabetes (T2D) treatment, due to their beneficial effect on weight and blood pressure. Three agents are approved for clinical use and they may differ on potency due to inhibition of only renal or both renal and bowel glucose transportation.

Controle inadequado da pressão arterial em pacientes com diabete melito tipo 2

BACKGROUND There is evidence indicating that blood pressure control is more effective in reducing macrovascular complications of diabetes mellitus (DM) than glycemic control. However, the reduction in BP to levels recommended by international guidelines is difficult in clinical practice. OBJECTIVE To assess the percentage of patients with both type 2 diabetes and hypertension (HBP) assisted in a tertiary hospital with adequate blood pressure control and to determine the clinical and laboratory factors related. METHODS Cross-sectional study with 348 patients with type 2 diabetes and hypertension assisted in the outpatient clinic of Endocrinology, Hospital de Clínicas de Porto Alegre. Patients underwent history assessment, physical examination, with measurement of blood pressure (BP), and samples were collected from blood and urine for laboratory analysis. Patients were divided into 3 three groups: optimal (< 130/80 mmHg), regular (130-139/80-89 mmHg) or inadequate blood pressure control (> or = 140/90 mmHg). RESULTS The mean age was 61.2 +/- 10.1 years (46% men, 80% white) and DM duration, 14.8 +/- 9.5 years. Eighteen per cent of the patients studied, 17% of patients had optimal BP value, 22% regular BP value and 61% inadequate BP value. Patients with inadequate BP control had longer diabetes duration, waist circumference and fasting glucose. The other variables were similar in 3 groups. CONCLUSION Most patients assessed had inadequate BP control. Higher BP values are associated with an adverse clinical profile, represented by longer diabetes duration, abdominal obesity, higher fasting glucose and chronic complications of diabetes.Resumen Fundamento: Hay evidencias indicando que el control de presion es mas efectivo en la reduccion de complicaciones macrovasculares de la diabetes melito (DM) que el control glucemico. Sin embargo, la reduccion de la PA para los niveles recomendados por las directrices es dificil en la practica clinica.Objetivo: Evaluar el porcentual de pacientes que presentaban simultaneamente DM tipo 2 y hipertension arterial sistemica (HAS), atendidos en hospital terciario, con control de presion adecuado, y determinar los factores clinicos y laboratoriales asociados.Metodos: Estudio transversal con 348 pacientes con DM tipo 2 y HAS atendidos en el ambulatorio de Endocrinologia del Hospital de Clinicas de Porto Alegre. Los pacientes fueron sometidos a anamnesis, examen fisico, con medicion de la presion arterial (PA), y se recolecto muestra de sangre y orina para analisis laboratorial. Los pacientes se dividieron en tres grupos: control de presion ideal (< 130/80 mmHg), regular (130-139/80-89 mmHg) o inadecuado (≥ 140/90 mmHg).Resultados: El promedio de edad fue de 61,2 ± 10,1 anos (el 46% hombre, 80% blanco) y la duracion del DM, 14,8 ± 9,5 anos. Del total de pacientes, el 17% expresaba valores ideales de PA, el 22% regular y el 61% inadecuados. Los pacientes con control inadecuado de la PA expresaban mayor duracion del DM, cintura abdominal y glucemia de ayuno. Las demas variables se asemejaron en los tres grupos.Conclusion: La mayoria de los pacientes evaluados presento control inadecuado de la PA. Valores mas elevados de PA estan asociados a un perfil clinico adverso, representado por mayor duracion del DM, obesidad abdominal, mayor glucemia de ayuno y complicaciones cronicas del DM. (Arq Bras Cardiol 2010;94(5):633-637)Palabras clave: Presion arterial, diabetes mellitus, obesidad, circunferencia abdominal, complicaciones de la diabetes.continua y para cada descenso de 10 mmHg en la PA sistolica se observa una reduccion promedia del 24% en el riesgo de cualquier complicacion relacionada al DM; del 32% en la mortalidad relacionada al DM; del 44% en los accidentes vasculares encefalicos y del 37% en las complicaciones microvasculares del DM