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BACKGROUND: Indigenous Brazilian peoples have faced an unparalleled increase in the rate of cardiovascular diseases following rapid nutritional transition to more urban diets. We aimed to conduct a systematic review and meta-analysis to evaluate the association between urbanisation (including data from Amazon rainforest deforestation) and cardiometabolic risk factors and outcomes. METHODS: In this systematic review and meta-analysis, we searched Pubmed, Embase, Web of Science, and Scopus for articles published in any language between the year 1950 and March 10, 2022. Studies conducted in Indigenous Brazilian adults that evaluated metabolic health were included. Data for deforestation was obtained by the Amazon Deforestation Monitoring Project. Cardiovascular mortality was obtained from the Brazilian Health registry. Two independent reviewers evaluated studies for risk of bias, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The main outcomes assessed were the prevalence of obesity and related cardiometabolic risk factors among Indigenous Brazilian peoples and its association with urbanisation. Summary data were extracted from published reports for the meta-analyses. We calculated pooled estimates of the prevalence of each cardiometabolic outcome by using a random-effects model (DerSimonian-Laird method). This study is registered with the International Prospective Register of Systematic Reviews, CRD42021285480. FINDINGS: 46 studies were identified, including a total of 20 574 adults from at least 33 Indigenous Brazilian ethnicities. Meta-analyses of the prevalence of obesity showed that there were higher rates of obesity (midwest region: 23% [95% CI 17-29]; and south region 23% [13-34]) and hypertension (south region: 30% [10-50]) in Indigenous peoples living in urban regions of Brazil, while the lowest rates of obesity (11% [95% CI 8-15]) and hypertension (1% [1-2]) were observed in those in the less urbanised (north) regions of Brazil. The prevalence of obesity was 3·5 times higher in participants living in urbanised Indigenous territories (28%) than in those living in lands with >80% native Amazon rainforest (8%). In meta-analyses that evaluated blood pressure level, there was no incremental change in blood pressure with ageing in Indigenous peoples who lived according to traditional lifestyle, in contrast to those living in urbanised regions. For Indigenous men with traditional lifestyles, systolic blood pressure changed from 109·8 mm Hg to 104·4 mm Hg between the youngest (<30 years) and the oldest (>60 years) age groups, and diastolic blood pressure changed from 69·8 mm Hg to 66·1 mm Hg. For Indigenous women with traditional lifestyles, systolic blood pressure was 100·0 mm Hg for the youngest age group with no changes for older age groups, and diastolic blood pressure was 62 mm Hg for the youngest age group with no changes for older age groups. For Indigenous men with urbanised lifestyles, systolic blood pressure changed from 117·3 mm Hg to 124·9 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 72·7 mm Hg to 76·4 mm Hg. For Indigenous women with urbanised lifestyles, systolic blood pressure changed from 110·0 mm Hg to 116·0 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 68·3 mm Hg to 74·0 mm Hg. For the years 1997 and 2019, the cardiovascular mortality rate in individuals living in the southeast region (the most urbanised) was 2·5 times greater than that observed in the north. Conversely, the incremental rise in cardiovascular mortality in the past two decades among Indigenous Brazilians living in the north or northeast (2·7 times increase) stands in stark contrast to the stable rates in those living in already urbanised regions. INTERPRETATION: The macrosocial changes of Indigenous peoples' traditional ways of living consequent to urbanisation are associated with an increased prevalence of adverse cardiometabolic outcomes. These data highlight the urgent need for environmental policies to ensure the conservation of the natural ecosystem within Indigenous territories, as well as the development of socio-health policies to improve the cardiovascular health of Indigenous Brazilians peoples living in urban areas. FUNDING: None.

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BACKGROUND AND AIMS: To evaluate the effect of lifestyle modification by adopting a DASH diet, with and without physical activity guidance, on blood pressure, glycemic control, lipid profile, weight, and body composition in older patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS AND RESULTS: For this randomized clinical trial, we recruited patients aged 60 years or older with T2DM and uncontrolled hypertension. One group (DASH) received only DASH dietary guidance, while the other group (DASHPED) received dietary guidance and encouragement to walk with a pedometer. Outcomes of interest were (1) blood pressure, (2) physical activity, (3) weight, body mass index (BMI), and body composition, and (4) biochemical variables. Measurements were taken at baseline and 16 weeks after the intervention. We included 35 patients in the analysis. At the end of the study, the DASHPED group had an mean increase in physical activity of 1721 steps/day. Both groups displayed significantly reduced weight, BMI, and waking diastolic pressures on ambulatory blood pressure monitoring after the intervention. A trend of reduced sleeping diastolic pressure was found in the DASHPED group. Changes in weight, BMI, muscle mass, body fat, waist-hip ratio, glycemic control, lipid profile, and insulin sensitivity did not differ between the groups. CONCLUSION: There was no difference in outcomes between the group that only dieted and the group that also performed increased physical activity, despite a significant increase in exercise. This reinforces the importance of dietary changes in immediate blood pressure control.

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BACKGROUND: Cancer patients present nutritional and complications risks during the postoperative period. Fasting contributes to surgical catabolic damage. This study evaluates the consequence of fasting time on the surgical outcomes of cancer patients undergoing elective surgeries. METHODS: Prospective cohort, evaluating two categories of patients according to postoperative fasting: less than or greater than 24 h. OUTCOMES: Hospitalization time, 28-day mortality, ICU stay and infection rates. DISCUSSION: We included 109 patients (57% men, 60 ± 15 years, BMI: 26 ± 5 kg/m2, SAPS3 43 ± 12), hepatectomy was the most frequent surgery (13.8%), and colon and rectum were the most common neoplasia (18.3%). The ICU stay was longer in postoperative fasting > 24 h (5.5 [4-8.25] vs. 3 [2-5] days, p < 0.001). Fasting > 24 h persisted as a risk factor for longer length of stay (LOS) in the ICU after adjustments. There were no differences in the mortality analysis within 28 days and total hospitalization time between groups. A tendency to experience more infections was observed in patients who fasted > 24 h (34.8% vs. 16.3%, p = 0.057). Onset of diet after the first 24 h postoperatively was a risk factor for longer ICU stay in cancer patients who underwent major surgeries.

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Antineoplastic treatments can negatively affect body composition, leading to metabolic derangements and worse clinical outcomes in breast cancer patients. This scoping review assesses body adiposity changes during breast cancer therapy. We included clinical and observational studies, published until the last search date in any language, with women aged >18 years, after breast cancer diagnosis, at any clinical stage and with any history of breast cancer treatment, who had body adiposity quantified by imaging tools at least twice during follow-up. In total, 17 studies were included (n = 1,009 individuals), six of which found a significant increase in body adiposity during treatment, two found a significant decrease, one presented divergent findings according to the imaging method and the analyzed body adiposity depots, and eight studies found no significant change in the outcome. Selective estrogen receptor modulators were associated with increased body adiposity, whereas aromatase inhibitors were associated with its decrease (n = 3). Chemotherapy was associated with increased body adiposity (n = 1), and monoclonal antibody with reduced brown adipose tissue activity (n = 1). Breast cancer treatment may have different effects on body adiposity, according to its mechanisms and protocols. Further studies are necessary to better elucidate this scenario.

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Objectives: The objective of this study is to synthesize the current literature about the relationship between the occurrence of diabetes insipidus (DI), its diagnosis criteria, and management after withdrawal of vasopressin (VP) in critically ill. Data sources: This scoping review followed the recommendations of Preferred Reporting Items for Systematic Review and Meta-Analyses for Scoping Review (PRISMA-ScR). The search literature was conducted in MEDLINE and EMBASE databases, until March 2022. A manual search was also conducted in order to include articles that were not identified in the initial search performed in the databases. Study selection and data extraction: The selection of studies and extraction of data were carried out in a paired and independent manner. There was no restriction regarding the language of publication of the included manuscripts. Data synthesis: The analysis included 17 studies (16 case reports and one retrospective cohort). All studies used VP, with a median time of drug infusion of 48 hours (IQR: 16-72) and DI incidence of 1.53%. The diagnosis of DI was based on diuresis output and concomitant hypernatremia or changes in serum sodium concentration, with median time to symptoms onset after discontinuation of VP of 5 hours (IQR: 3-10). The treatment of DI consisted mainly of fluid management and the use of desmopressin. Conclusions: DI after VP withdrawal was present in 51 patients described in 17 studies, but diagnosis and management varied among each report. Using the available data, we propose a diagnosis suggestion and a flowchart for managing patients with DI after withdrawal of VP in the Intensive Care Unit. Multicentric collaborative research is urgently needed to obtain more quality data on this topic. How to cite this article: Pérsico RS, Viana MV, Viana LV. Diabetes Insipidus after Vasopressin Withdrawal: A Scoping Review. Indian J Crit Care Med 2022;26(7):846-852.

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BACKGROUND: Parenteral nutrition (PN) is an available option for nutritional therapy and is often required in the hospital setting to overcome malnutrition. OBJECTIVES: The aim of this study was to assess whether PN is associated with an increased risk of mortality or infectious complications in all groups of hospitalized patients compared with those receiving other nutritional support strategies. METHODS: For this systematic review and meta-analysis MEDLINE, Embase, Cochrane Central, Scopus, clinicaltrials.gov, and Web of Science were searched for randomized controlled trials (RCTs) and observational studies with parallel groups that explored the effect of PN on mortality and infectious complications, published until March 2021. Two independent reviewers extracted the data and assessed the risk of bias. Fixed-effects meta-analysis was performed to compare the groups from RCTs. Trial sequential analysis (TSA) was used to identify whether the results were sufficient to reach definitive conclusions. RESULTS: Of the 83 included studies that compared patients receiving PN with those receiving other strategies, 67 RCTs were included in the meta-analysis. PN was not associated with a higher risk of mortality (RR: 1.01; 95% CI: 0.95, 1.07). On the other hand, PN was associated with a higher risk of infectious events (RR: 1.23; 95% CI: 1.12, 1.36). PN was specifically associated with abdominal infection and catheter infection. The TSA showed that there were sufficient data to make numerical conclusions about mortality, any infectious event, and abdominal infectious complications. CONCLUSIONS: This study suggests that although PN is not associated with greater mortality in hospitalized patients, it is associated with infectious complications. Through TSA, definite conclusions about survival and infection rates could be made.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42018075599.

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BACKGROUND: Uncoupling protein 2 (UCP2) plays an important role in energy expenditure regulation. Previous studies have associated the common -866G/A (rs659366) and Ins/Del polymorphisms in the UCP2 gene with metabolic and obesity-related phenotypes. However, it is still unclear whether these polymorphisms influence weight loss after bariatric surgery. OBJECTIVES: To investigate whether UCP2 -866G/A and Ins/Del polymorphisms are associated with weight loss outcomes after bariatric surgery. SETTING: Longitudinal study in a university hospital. METHODS: We retrospectively evaluated 186 patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for clinical and laboratory characteristics in the preoperative period, 6, 12, and 18 months after RYGB. The -866G/A (rs659366) polymorphism was genotyped using real-time PCR, while the Ins/Del polymorphism was genotyped by direct separation of PCR products in 2.5% agarose gels. RESULTS: Patients with the -866A/A genotype showed higher body mass index (BMI) after 6, 12, and 18 months of surgery and excess body weight after 6 and 12 months compared with G/G patients. They also showed lower excess weight loss (EWL%) after 6 and 12 months of surgery. Ins allele carriers (Ins/Ins + Ins/Del) had lower delta (Δ) BMI 12 months after surgery compared with Del/Del patients. Accordingly, patients carrying haplotypes with ≥2 risk alleles of these polymorphisms had higher BMI and excess weight and lower EWL% during follow-up. CONCLUSION: UCP2 -866A/A genotype is associated with higher BMI and excess weight and lower EWL% during an 18-month follow-up of patients who underwent RYGB, while the Ins allele seems to be associated with lower ΔBMI 12 months after surgery. Further studies are needed to confirm the associations of the -866G/A and Ins/Del polymorphisms with weight loss after bariatric surgery.

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Observational and experimental data reinforce the concept that vitamin D is associated with the pathogenesis of arterial hypertension. We investigated the effect of a single dose of 100,000 IU of cholecalciferol, in office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM) in patients with type 2 diabetes mellitus (DM), hypertension, and hypovitaminosis D. Forty-three patients were randomized to a placebo or cholecalciferol group. BP was assessed by office measurements and 24-h ABPM, before and after intervention. At week 8, a greater decrease in median ABPM values was observed in cholecalciferol supplementation than in the placebo group for systolic 24-h (- 7.5 vs. - 1; P = 0.02), systolic daytime (- 7 vs. - 1; P = 0.007), systolic nighttime (- 7.0 vs. 3; P = 0.009), diastolic 24-h (- 3.5 vs. - 1; P = 0.037), and daytime DBP (- 5 vs. 0; P = 0.01). Office DBP was also reduced after vitamin D supplementation. A single dose of vitamin D3 improves BP in patients with type 2 diabetes, hypertension, and vitamin D insufficiency, regardless of vitamin D normalization. Vitamin D supplementation could be a valuable tool to treat patients with type 2 DM, hypertension, and hypovitaminosis D.Trial registration: Clinicaltrials.gov NCT02204527.

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INTRODUCTION: New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS: SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. REGISTRATION: PROSPERO CRD42019132807.

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OBJECTIVES: The aim of this study was to establish the prevalence of sarcopenia and associated factors in elderly patients with type 2 diabetes mellitus (DM) according to 2010 (EWGSOP1) and 2018 (EWGSOP2) European consensus. DESIGN: Cross-sectional study. PARTICIPANTS: Elderly outpatients ≥60 years with type 2 DM and able to walk were recruited at the DM ambulatory care center of a public hospital in Porto Alegre from 2017 to 2018. MATERIALS AND METHODS: The diagnosis of sarcopenia was performed according to EWGSOP1 and EWGSOP2. Muscle mass (MM) was assessed using bioelectrical impedance (BIA). Muscle strength (MS) was assessed using the handgrip strength (HS) test and physical performance (PP) by timed-up-and-go (TUG) test. RESULTS: We included 242 patients with 68.3 ± 5.6 years, 54% women, 78% white, DM duration 14(8-22) years, BMI 29.5 ± 4.5 kg/m2, and HbA1c 7.8 ± 1.5%. Overall prevalence of sarcopenia was 21%. In EWGSOP1 it was 16.9%. The GLM Poisson model was used to assess sarcopenia. Male sex increased the prevalence of sarcopenia by 33% (3.330 [1.747-6.350]; p < .001), and walking >5401 steps/day had a protective effect of 70% for the prevalence of sarcopenia (0.306 [0.127-0.739]; p = .029). Finally, age had an impact of 6% on prevalence of sarcopenia (1.06 [1.015-1.108]; p = .009) according to EWGSOP1. On the other hand, the prevalence was 7%, women had more sarcopenia (88%), and BMI was lower in the sarcopenic group when defined according to EWGSOP2. CONCLUSIONS: The prevalence of sarcopenia was more than double when comparing EWGSOP1 (16.9%) and EWGSOP2 (7%). We believe that the difference in prevalence is due to modifications in MM and MS criteria. According to EWGSOP1, walking may have protective role in the prevalence of sarcopenia in elderly type 2 DM individuals.

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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.

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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.

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OBJECTIVE: To analyze possible associations of dietary components, especially protein intake, with blood pressure (BP) during ambulatory BP monitoring (ABPM) in patients with type 2 diabetes. METHODS: In this cross-sectional study, BP of outpatients with type 2 diabetes was evaluated by 24-hour ABPM (Spacelabs 90207) and usual diet by 3-day weighed diet records. Patients were divided into 2 groups according to their daytime ABPM: uncontrolled BP (systolic BP ≥ 135 mmHg or diastolic BP ≥ 85 mmHg) and controlled BP (systolic BP < 135 mmHg and diastolic BP < 85 mmHg). Logistic regression models unadjusted and adjusted for possible confounders (covariates) were used to analyze the association of protein and uncontrolled BP. RESULTS: A total of 121 patients with type 2 diabetes aged 62.3 years, 54.5% of whom were women, were studied. The uncontrolled BP group had higher glycated hemoglobin (HbA1C) values (8.4 ± 2.0 vs 7.6 ± 1.3%; p = 0.04) and consumed more protein (20.0 ± 3.8 vs 18.2 ± 3.6% of energy; p = 0.01) and meat, (2.6 [1.45, 2.95] vs 2.0 [1.49, 2.90] g/kg weight; p = 0.04) than the controlled BP group. In a multivariate analysis, protein intake (% of energy) increased the chance for uncontrolled BP (odds ratio [OR] = 1.16; 95% confidence interval [CI], 1.02, 1.30; p = 0.02), adjusted for body mass index (BMI), HbA1C, low-density lipoprotein (LDL) cholesterol, number of antihypertensive medications, and ethnicity. Meat consumption higher than 3.08 g/kg weight/day more than doubled the chance for uncontrolled BP (OR = 2.53; 95% CI, 1.01, 7.60; p = 0.03). CONCLUSION: High protein intake and meat consumption were associated with high daytime ABPM values in patients with type 2 diabetes. Reducing meat intake might represent an additional dietary intervention in hypertensive patients with type 2 diabetes.

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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/m(2)) 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.

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BACKGROUND: Hypertension 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. METHODS: A 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; ß-adrenergic blocking agent and calcium channel blocking agent if BP >130/80 mmHg. RESULTS: Seventy-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. CONCLUSIONS: A 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 REGISTRATION: ClinicalTrials.gov: NCT06260.

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BACKGROUND: The American Diabetes Association (ADA) has published several diabetes treatment algorithms, but none have been tested in real-life settings. The aim of this study is to analyze the feasibility of achieving and/or maintaining HbA1c levels <7.0% using current diabetes treatment guidelines and the resources available in the public health care system of Brazil. METHODS: A one-year, single-arm interventional study was conducted with type 2 diabetes patients in a primary care unit. Intervention consisted of intensification of lifestyle changes and sequential prescription of drugs based on ADA guidelines using the medications available through the publicly funded Unified Health System (Sistema Único de Saúde, SUS). RESULTS: Ninety patients (age: 62.7±10.4 years; diabetes duration: 8.2±9.1 years) completed the trial. During the intervention period, increases were observed in number of oral antidiabetic agent (OAD) classes per patient (1.50±0.74 vs. 1.67±0.7; p=0.015), OAD pills per patient (2.64±1.89 vs. 3.33±2.23 pills/patient; p <0.001), insulin dosage (0.20±0.29 vs.0.50±0.36 UI/kg/day; p=0.008) and number of patients on insulin (19 [21%] vs. 31 [34%]; p<0.01), but no improvement in HbA1c (7.2±1.6% vs. 7.3±1.5%; p=0.453) or frequency of patients on target, defined as HbA1c <7% (53.3% vs. 48.9%; p=0.655). Patients with baseline HbA1c <7% had a small increase in HbA1c during the trial (6.3±0.4 vs. 6.7±0.9%; p=0.002). No such change was observed in those with baseline HbA1c ≥7%. CONCLUSIONS: In this group of patients with a mean baseline HbA1c of 7.2%, implementation of 2006/2009 ADA/EASD guidelines led to achievement of the therapeutic goal of HbA1c <7% in a small proportion of patients.

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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 patient's clinical characteristics. PRIMARY FUNDING SOURCE: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacao de Aperfeicoamento de Pessoal de Nível Superior.

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