Luciana Verçoza Viana

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.

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.

Poor glycaemic control in Brazilian patients with type 2 diabetes attending the public healthcare system: a cross-sectional study

Objectives To describe the clinical profile of Brazilian patients with type 2 diabetes attending the public healthcare system and identify factors associated with poor glycaemic control. Design Cross-sectional study. Setting 14 centres in five regions of Brazil, including primary care units and outpatient clinics of University Hospitals. Participants Patients with type 2 diabetes attending outpatient clinics of public healthcare system. Main outcome measured Glycated haemoglobin (HbA1c), centrally measured by high-performance liquid chromatography (National Glycohemoglobin Standardization Program certified). Results A total of 5750 patients aged 61±10 years, with 11±8 years of diabetes duration (66% women, 56% non-white, body mass index: 28.0±5.3 kg/m2) were analysed. Mean HbA1c was 8.6±2.2%, and median HbA1c was 8.1% (6.9% to 9.9%). HbA1c <7% was observed in only 26% of patients. Mean HbA1c was higher (p < 0.01) in the North (9.0±2.6%) and Northeast (8.9±2.4%) than in the Midwest (8.1±2%), Southeast (8.4±2.1%) and South regions (8.3±1.9%). Using the cut-off value of HbA1c above the median, age (0.986 (0.983 to 0.989)), white ethnicity (0.931 (0.883 to 0.981)) and being from Midwest region (0.858 (0.745 to 0.989)) were protective factors, while diabetes duration (1.015 (1.012 to 1.018)), use of insulin (1.710 (1.624 to 1.802)) and living in the Northeast region (1.197 (1.085 to 1.321)) were associated with HbA1c >8%. Conclusions The majority of Brazilian patients with type 2 diabetes attending the public healthcare system had HbA1c levels above recommended targets. The recognition of Northeast residents and non-white patients as vulnerable populations should guide future policies and actions to prevent and control diabetes.

Interventions to improve patients' compliance with therapies aimed at lowering glycated hemoglobin (HbA1c) in type 1 diabetes: systematic review and meta-analyses of randomized controlled clinical trials of psychological, telecare, and educational interventions

BackgroundBrazilian records on glycemic control in patients with type 1 diabetes show treatment efficacy. Poor patient adherence to therapeutic proposals influences these results and can be associated with social, psychological, and economic aspects, besides others factors. The aim of this study was to evaluate the efficacy of psychological, telecare, and educational interventions to improve treatment compliance among patients with type 1 diabetes. Compliance was assessed indirectly using reduction of glycated hemoglobin (HbA1c) as the principal outcome measure.MethodsSystematic review and meta-analyses of randomized controlled clinical trials (RCTs) were performed using Medline, Embase, Cochrane and Scopus databases up to April 2015. The following medical subject headings were used: Diabetes Mellitus, Type 1, Patient Compliance or Adherence, Hemoglobin A, glycated, and Randomized Controlled Trial. The principal outcome was change in HbA1c between baseline and follow-up. Where appropriate, trials were combined in meta-analysis using fixed effects models.ResultsFrom 191 articles initially identified, 57 were full text reviewed, and 19 articles met the inclusion criteria providing data from 1782 patients (49.4 % males, age 18 years). The RCTs (2 to 24 months in duration) were divided into four groups according to type of intervention: psychology (seven studies; 818 patients), telecare (six studies; 494 patients); education (five studies; 349 patients), and psychoeducation (one study; 153 patients). All studies reported some type of adherence measurement of the interventions. Decrease in HbA1c was observed after psychology (MD −0.310; 95 % CI, −0.599 to −0.0210, P = 0.035) but not after telecare (MD −0.124 %; 95 % CI, −0.268, 0.020; P = 0.090) or educational (MD −0.001; 95 % CI, −0.202, 0.200; P = 0.990) interventions.ConclusionPsychological approaches to improve adherence to diabetes care treatment modestly reduced HbA1c in patients with type 1 diabetes; telecare and education interventions did not change glycemic control. However, the limited number of studies included as well as their methodological quality should be taken into account.

Prediction of cardiovascular events, diabetic nephropathy, and mortality by albumin concentration in a spot urine sample in patients with type 2 diabetes

AIMS To analyze in a random urine spot the predictive value of urinary albumin concentration (UAC) for cardiovascular events, diabetic nephropathy (DN), and death in patients with type 2 diabetes. METHODS In this cohort, urinary albumin (immunoturbidimetry) was measured as 24-h urinary albumin excretion (UAE) and, in a random spot urine, as UAC and albumin:creatinine ratio (ACR). Primary outcomes were: 1) cardiovascular events, 2) DN defined as a composite outcome [macroalbuminuria and/or decreased glomerular filtration rate (GFR) <60 ml/min/1.73 m²], and 3) death. RESULTS A total of 199 type 2 diabetic patients, aged 59.9 ± 9.9 years, were followed for 6.1 ± 2.7 years. UAC ≥14.4 mg/l, as determined by ROC curve, predicted DN and prediction for this and other outcomes were compared with traditional microalbuminuria cutoffs for ACR and UAE. The outcomes frequency was: cardiovascular events = 26.4%, DN = 31.7% (23.5% decreased GFR; 13.6% macroalbuminuria) and death = 8.50%. In Cox analyses, UAC ≥14 mg/l increased the risk (hazard ratio, HR) for cardiovascular events 3.25 times (95% CI 1.43-7.38; P = 0.005), 4.30 for DN composite outcome (95% CI 2.22-8.32; P <0.001), and 5.51 for death (95% CI 1.16-26.22; P = 0.032). Corresponding HRs of ACR ≥30 mg/g were: 2.89 (95% CI 1.29-6.45; P = 0.009) for cardiovascular events, 4.67 (95% CI 2.34-9.34; P <0.001) for DN composite outcome and 5.07 (95% CI 1.01-24.88; P = 0.049) for death. HRs of UAE ≥30 mg/24-h were: 2.20 (95% CI 2.08-2.49; P = 0.030) for cardiovascular events, 6.76 (95% CI 3.32-13.77; P <0.001) for DN composite outcome, and 2.47 (95% CI 0.72-8.42; P = 0.150) for death. CONCLUSIONS In conclusion, random UAC ≥14 mg/l predicted cardiovascular events, diabetic nephropathy, and mortality just as well as ACR. UAC may be used to assess cardiovascular and renal risks in patients with type 2 diabetes.

Effects of the DASH Diet and Walking on Blood Pressure in Patients With Type 2 Diabetes and Uncontrolled Hypertension: A Randomized Controlled Trial

Data on the potential beneficial effects of combining diet and exercise on blood pressure (BP) are still scarce. A 4‐week randomized controlled clinical trial was undertaken in 40 hypertensive patients with type 2 diabetes with uncontrolled blood pressure (BP) in office and daytime ambulatory BP monitoring (ABPM). Patients were assigned to follow a Dietary Approaches to Stop Hypertension (DASH) diet associated with advice to increase walking using a pedometer (intervention group) or a diet based on the American Diabetes Association recommendations (control group). The lifestyle intervention caused a greater ABPM (mm Hg) reduction in systolic 24‐hour, diastolic 24‐hour, nighttime systolic, daytime systolic, and daytime diastolic measurements than observed in the control group. In the intervention group there was a decrease in urinary sodium and an increase in urinary potassium, plasma aldosterone, and the number of steps per day (P<.05). The DASH diet and increased walking were associated with clinically significant reductions in ABPM values in hypertensive patients with type 2 diabetes.

Plasma glucose and insulin responses after consumption of breakfasts with different sources of soluble fiber in type 2 diabetes patients: a randomized crossover clinical trial

Background: The amount and quality of carbohydrates are important determinants of plasma glucose after meals. Regarding fiber content, it is unclear whether the intake of soluble fibers from foods or supplements has an equally beneficial effect on lowering postprandial glucose.Objective: The aim of our study was to compare the acute effect of soluble fiber intake from foods or supplements after a common meal on postprandial plasma glucose and plasma insulin in patients with type 2 diabetes (T2D).Design: A randomized crossover clinical trial was conducted in patients with T2D. Patients consumed isocaloric breakfasts (mean ± SD: 369.8 ± 9.4 kcal) with high amounts of fiber from diet food sources (total fiber: 9.7 g; soluble fiber: 5.4 g), high amounts of soluble fiber from guar gum supplement (total fiber: 9.1 g; soluble fiber: 5.4 g), and normal amounts of fiber (total fiber: 2.4 g; soluble fiber: 0.8 g). Primary outcomes were postprandial plasma glucose and insulin (0-180 min). Data were analyzed by repeated measures ANOVA and post hoc Bonferroni test.Results: A total of 19 patients [aged 65.8 ± 7.3 y; median (IQR), 10 (5-9) y of T2D duration; glycated hemoglobin 7.0% ± 0.8%; body mass index (in kg/m2) 28.2 ± 2.9] completed 57 meal tests. After breakfast, the incremental area under the curve (iAUC) for plasma glucose [mg/dL · min; mean (95% CI)] did not differ between high fiber from diet (HFD) [7861 (6257, 9465)] and high fiber from supplement (HFS) [7847 (5605, 10,090)] (P = 1.00) and both were lower than usual fiber (UF) [9527 (7549, 11,504)] (P = 0.014 and P = 0.037, respectively). iAUCs [μIU/mL · min; mean (95% CI)] did not differ (P = 0.877): HFD [3781 (2513, 5050)], HFS [4006 (2711, 5302), and UF [4315 (3027, 5603)].Conclusions: Higher fiber intake was associated with lower postprandial glucose at breakfast, and the intake of soluble fiber from food and supplement had a similar effect in patients with T2D. This trial was registered at clinicaltrials.gov as NCT02204384.

Hypertension management algorithm for type 2 diabetic patients applied in primary care.

BackgroundHypertension frequently coexists with type 2 diabetes (DM), and increases the risk of cardiovascular outcomes. The aim of the study was to obtain/maintain blood pressure (BP) goals (ADA/JNC 7) according to a stepwise algorithm using the medication supplied by the Brazilian government.MethodsA one-year, single-arm interventional study conducted with type 2 diabetes patients. Intervention consisted of intensification of lifestyle changes and sequential prescription of drugs: diuretic; ACE inhibitors; β-adrenergic blocking agent and calcium channel blocking agent if BP >130/80 mmHg.ResultsSeventy-eight patients completed the trial. During intervention, the number of antihypertensive tablets rose (3.6 ± 3.5 vs. 5.9 ± 3.5 pills/patient; p <0.001), as the number of antihypertensive classes increased (1.8 ± 1.0 vs. 2.70 ± 1.2; p < 0.01) and the overall drop of BP was 11 mmHg for SBP (145.0 ± 22.8 vs. 133.7 ± 20.9 mmHg; p < 0.01) and 5 mmHg for DBP (78.7 ± 11.5 vs. 73.7 ± 10.5 mmHg; p = 0.001). Although the number of patients with BP in target almost doubled [14 (18.7%) vs. 30 (38.5%) p = 0.008], less than 40% of the patients achieved the proposed goals.ConclusionsA BP algorithm applied to type 2 diabetic and hypertensive patients is able to lower BP, however more than half of the patients did not achieve the ADA/JNC 7 targets demonstrating the complexity of BP control in this population.Trial registrationClinicalTrials.gov: NCT06260

Acquired Factor VIII and von Willebrand Factor (aFVIII/VWF) Deficiency and Hypothyroidism in a Case With Hypopituitarism

This article reports a female who presented with bleeding, acquired factor VIII and von Willebrand factor (aFVIII-VWF) deficiency, and central deficiency in the thyroid and adrenal axis (Sheehan’s syndrome). After starting hormone replacement therapy, relief of bleeding manifestations was associated with correction of both FVIII and VWF to normal. This report draws attention to a rare association between the acquired form of von Willebrand disease and hypothyroidism of central origin.

Effects of individual micronutrients on blood pressure in patients with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials

To investigate the effects of micronutrients on blood pressure (BP) in patients with type 2 diabetes through a systematic review and meta-analysis, randomized clinical trials (RCTs) of the effects of individual micronutrients on BP in patients with type 2 diabetes were searched in the Medline, Embase, Cochrane, and Clinical Trials.gov databases through April 2016. From the 28,164 studies, 11 RCTs (13 interventions, 723 patients, 54% males) with 3 to 52 weeks of follow-up were classified according to the type of micronutrient intervention: sodium (n = 1), vitamin C (n = 2), vitamin D (n = 7), and magnesium (n = 1). The available data enabled us to perform meta-analyses of vitamins C and D. Vitamin C reduced diastolic BP [WMD −2.88 mmHg (95%CI −5.31, −0.46; P = 0.020)] but not systolic BP [WMD −3.93 mmHg (95%CI −14.78, 6.92; P = 0.478)]. Vitamin D caused a reduction of 4.56 mmHg (WMD; 95%CI −7.65, −1.47; P = 0.004) for systolic BP and 2.44 mm Hg (WMD; 95%CI −3.49, −1.39; P < 0.001) for diastolic BP. In conclusion, vitamin D and possibly vitamin C have beneficial effects on BP in patients with type 2 diabetes. These interventions might represent a novel approach to the treatment of hypertension in these patients.