Mirela Jobim de Azevedo

The Receiver Operating Characteristics Curve in the Evaluation of a Random Urine Specimen as a Screening Test for Diabetic Nephropathy

OBJECTIVE To assess the performance of measurements of urinary albumin concentration (UAC) and urinary albumin:creatinine ratio (UACR) in a diurnal random urine specimen (RUS) for the screening of diabetic nephropathy. RESEARCH DESIGN AND METHODS A total of 95 ambulatory NIDDM patients (49 women, ages 40–75 years) collected 123 RUSs during the morning after completing a timed 24-h urine collection. Albumin was measured by immunoturbidimetry. According to timed urinary albumin excretion rate (UAER) measured in the 24-h collection (criterion standard), samples were classified as normoalbuminuric (UAER < 20 μg/min; n = 54), microalbuminuric (UAER 20–200 μg/min; n = 44), and macroalbuminuric (UAER > 200 μg/min; n = 25). The receiver operating characteristics (ROC) curve approach was used. The ROC curves of UAC and UACR in RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 98) and macroalbuminuria (micro- and macroalbuminuric samples; n = 69) were plotted. RESULTS Spearmans coefficients of correlation of 24-h UAER vs. UAC and UACR were 0.91 and 0.92, respectively (P < 0.001). The calculated areas (± SE) under the ROC curves to screen microalbuminuria for UAC (0.9766 ± 0.015) and UACR (0.9689 ± 0.014) were similar (P > 0.05) as were the corresponding areas for macroalbuminuria (0.9868 ± 0.0094 and 0.9614 ± 0.0241, respectively; P > 0.05). The first point with 100% sensitivity and the point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 16.9 and 33.6 mg/l for UAC and 15.0 and 26.8 mg/g for UACR; for macroalbuminuria 174.0 and 296.2 mg/l for UAC and 116.0 and 334.3 mg/g for UACR, respectively. CONCLUSIONS Albumin measurements (UAC and UACR) in an RUS presented almost perfect accuracy for the screening of micro- and macroalbuminuria and UAC measured in an RUS is simpler and less expensive than UACR and UAER. It is suggested as a valid test for use in screening for diabetic nephropathy.

Diabetes Melito: Diagnóstico, Classificação e Avaliação do Controle Glicêmico

Diabetes mellitus and other categories of impaired glucose tolerance are frequent in the adult population and are associated with an increased risk for cardiovascular disease and microvascular complications. The diagnosis of these entities should be performed early and using sensitive and accurate methods, since lifestyle changes and correction of hyperglycemia may delay the incidence of diabetes and its complications. Glucose tolerance test is the reference method and the diagnosis of diabetes and impaired glucose tolerance are established when the 2h plasma glucose after an oral intake of 75g of glucose is ³200mg/dl or ³140 and <200mg/dl, respectively. When it is not possible to perform this test, fasting plasma glucose levels ³126mg/dl or ³110 and <126mg/dl, respectively, are used to establish the diagnosis of diabetes and impaired fasting plasma glucose. Glycohemoglobin should not be used for the diagnosis but it is the reference method for evaluation of the long-term glucose control. The etiological classification of diabetes mellitus includes 4 categories: type 1 diabetes, type 2 diabetes, other specific types of diabetes and gestational diabetes. The assignment of the patient in each category usually is made on clinical grounds, however in some case the measurement of C-peptide and autoantibodies are necessary.

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.

Diabetic Retinopathy Predicts All-Cause Mortality and Cardiovascular Events in Both Type 1 and 2 Diabetes: Meta-analysis of observational studies

OBJECTIVE The prognostic significance of diabetic retinopathy (DR) for death and cardiovascular (CV) outcomes is debated. We investigated the association of DR with all-cause mortality and CV events in patients with diabetes by a systematic review and meta-analysis. RESEARCH DESIGN AND METHODS The electronic databases Medline and Embase were searched for cohort studies that evaluated DR in type 2 or type 1 diabetic patients and reported total mortality and/or fatal and nonfatal CV events, including myocardial infarction, angina pectoris, coronary artery bypass graft, ischemic changes on a conventional 12-lead electrocardiogram, transient ischemic attack, nonfatal stroke, or lower leg amputation. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS The analysis included 20 studies that fulfilled the inclusion criteria, providing data from 19,234 patients. In patients with type 2 diabetes (n = 14,896), the presence of any degree of DR increased the chance for all-cause mortality and/or CV events by 2.34 (95% CI 1.96–2.80) compared with patients without DR. In patients with type 1 diabetes (n = 4,438), the corresponding odds ratio was 4.10 (1.50–11.18). These associations remained after adjusting for traditional CV risk factors. DR was also predictive of all-cause mortality in type 2 diabetes (odds ratio 2.41 [1.87–3.10]) and type 1 diabetes (3.65 [1.05–12.66]). CONCLUSIONS The presence of DR was associated with an increased risk of all-cause mortality and CV events in both type 2 and type 1 diabetic patients.

Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials

This systematic review with meta-analysis of randomized controlled trials (RCT) aimed to analyze the effect of fiber intake on glycemic control in patients with type 2 diabetes. Databases were searched up to November 2012 using the following medical subject headings: diabetes, fiber, and randomized controlled trial. Absolute changes in glycated hemoglobin and fasting plasma glucose were reported as differences between baseline and end-of-study measures. Pooled estimates were obtained using random-effects models. Of the 22,046 articles initially identified, 11 (13 comparisons; range of duration, 8-24 weeks) fulfilled the inclusion criteria, providing data from 605 patients. High-fiber diets, including diets with foods rich in fiber (up to 42.5 g/day; four studies) or supplements containing soluble fiber (up to 15.0 g/day; nine studies), reduced absolute values of glycated hemoglobin by 0.55% (95% CI -0.96 to -0.13) and fasting plasma glucose by 9.97 mg/dL (95% CI -18.16 to -1.78). In conclusion, increased fiber intake improved glycemic control, indicating it should be considered as an adjunctive tool in the treatment of patients with type 2 diabetes.

Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis

Objective To investigate the association of coronary artery calcium score with all cause mortality and cardiovascular events in people with type 2 diabetes. Design Systematic review and meta-analysis of observational studies. Data sources Studies were identified from Embase, PubMed, and abstracts from the 2011 and 2012 annual meetings of the American Diabetes Association, European Association for the Study of Diabetes, American College of Cardiology, and American Heart Association (2011). Eligibility criteria Prospective studies that evaluated baseline coronary artery calcium score in people with type 2 diabetes and subsequent all cause mortality or cardiovascular events (fatal and non-fatal). Data extraction Two independent reviewers extracted the data. The predictive value of the coronary artery calcium score was assessed by random effects model. Results Eight studies were included (n=6521; 802 events; mean follow-up 5.18 years). The relative risk for all cause mortality or cardiovascular events, or both comparing a total coronary artery calcium score of ≥10 with a score of <10 was 5.47 (95% confidence interval 2.59 to 11.53; I2=82.4%, P<0.001). The overall sensitivity of a total coronary artery calcium score of ≥10 for this composite outcome was 94% (95% confidence interval 89% to 96%), with a specificity of 34% (24% to 44%). The positive and negative likelihood ratios were 1.41 (95% confidence interval 1.20 to 1.66) and 0.18 (0.10 to 0.30), respectively. For people with a coronary artery calcium score of <10, the post-test probability of the composite outcome was about 1.8%, representing a 6.8-fold reduction from the pretest probability. Four studies evaluated cardiovascular events as the outcome (n=1805; 351 events). The relative risk for cardiovascular events comparing a total coronary artery calcium score of ≥10 with a score of <10 was 9.22 (2.73 to 31.07; I2=76.7%, P=0.005). The positive and negative likelihood ratios were 1.67 (1.30 to 2.17) and 0.11 (0.04 to 0.29), respectively. Conclusion In people with type 2 diabetes, a coronary artery calcium score of ≥10 predicts all cause mortality or cardiovascular events, or both, and cardiovascular events alone, with high sensitivity but low specificity. Clinically, the finding of a coronary artery calcium score of <10 may facilitate risk stratification by enabling the identification of people at low risk within this high risk population.

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.

Dietary Intervention in Patients With Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials on Maternal and Newborn Outcomes

OBJECTIVE Diet is the cornerstone treatment of patients with gestational diabetes mellitus (GDM), but its role in maternal and newborn outcomes has been scarcely studied. The purpose of this study was to analyze the efficacy of dietary interventions on maternal or newborn outcomes in patients with GDM. RESEARCH DESIGN AND METHODS A systematic review and meta-analysis of randomized clinical trials (RCTs) of dietary intervention in GDM or pregnancy with hyperglycemia was performed. MEDLINE, Embase, ClinicalTrials.gov, Cochrane, and Scopus were searched through to March 2014. The main evaluated maternal outcomes were proportion of patients using insulin and proportion of cesarean delivery; the newborn outcomes were proportion of macrosomia and hypoglycemia and newborn weight. RESULTS From 1,170 studies, nine RCTs, including 884 women aged 31.5 years (28.7–33.2) with 27.4 weeks (24.1–30.3) of gestation, were eligible. We divided the RCTs according to the type of dietary intervention: low glycemic index (GI) (n = 4; 257 patients), total energy restriction (n = 2; 425 patients), low carbohydrates (n = 2; 182 patients), and others (n = 1; 20 patients). Diet with low GI reduced the proportion of patients who used insulin (relative risk 0.767 [95% CI 0.597, 0.986]; P = 0.039) and the newborn birth weight (weight mean differences −161.9 g [95% CI −246.4, −77.4]; P = 0.000) as compared with control diet. Total restriction and low carbohydrate diets did not change either maternal or newborn outcomes. CONCLUSIONS A low GI diet was associated with less frequent insulin use and lower birth weight than control diets, suggesting that it is the most appropriate dietary intervention to be prescribed to patients with GDM.

Chicken and Fish Diet Reduces Glomerular Hyperfiltration in IDDM Patients

OBJECTIVE To compare the effect of a normal protein diet (test diet) in which chicken and fish were substituted for red meat with a low-protein diet (LPD) on glomerular nitration rate (GFR) in normoalbuminuric insulin-dependent-diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS A crossover randomized clinical trial was performed in 15 normoalbuminuric IDDM patients, 9 normofiltering, and 6 hyperfiltering patients. They followed three diets for a 3-week period each: a usual diet (UD), an LPD (0.5 g · kg–1 · day–1 of proteins, 7% calories as protein, 33% as fat, and 60% as carbohydrates), and a normoproteic isocaloric test diet in which white meat (chicken and fish) was substituted for red meat of the UD. At the end of each diet, a clinical evaluation and measurements of GFR (51Cr-ethylenediaminetetraacetate (EDTA) single injection technique), urinary albumin excretion (UAE), and plasma amino acids were performed. Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian. RESULTS In all diabetic patients, GFR after the LPD (114.9 ± 16.5ml · min–1 · 1.73 m∼2) and after the test diet (122.7 ± 16.7 ml · min–1 · 1.73 m∼2) was significantly lower than after the UD (132.0 ± 27.7 ml · min–1 · 1.73 m∼2) (P = 0.001). Similar results were found in the hyperfiltering group: after UD = 161.1 ± 15.4 ml · min–1 · 1.73 m–2, after LPD = 129.8 ± 9.0 ml-min–1 · 1.73 m–2, and after the test diet = 136.5 ± 3.1 ml · min–1 · 1.73 m–2, (P < 0.001). In the normofiltering group, no significant changes in GFR were observed after the three diets. Metabolic control, nutritional indexes, blood pressure (BP), and UAE did not change after the three diets in all patients. CONCLUSIONS A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients. The GFR reduction after this diet is similar to that observed after an LPD.

Dietary factors and metabolic syndrome

The role of diet in metabolic syndrome (MS) has been studied regarding each one of its components: obesity, high blood pressure, dyslipidemia, and abnormal glucose metabolism. However, few studies evaluated the effects of diet in the presence of MS as a unique independent disease. The aim of this manuscript was to review the role of dietary factors and dietary recommendations for MS. Recently some studies demonstrated that intake of whole-grain foods were negatively associated with MS. Foods with high glycemic index were positively associated with insulin resistance and the prevalence of MS. Following a Mediterranean-style diet caused a reduction in the number of MS components. Also, the adoption of the DASH diet improved the profile of all MS components. A total daily energy intake to obtain and/or to maintain a desirable weight is recommended for patients with MS. The fat content, especially from saturated fat, and cholesterol must be reduced and the intake of whole-grain foods, fruits, and vegetables must be increased. Probably, dietary fibers have an important role in the management of MS. New studies to evaluate the role of diet in the presence and development of MS are needed.