Jorge L Gross

Hospital De Clínicas De Porto Alegre, Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil

Are you Jorge L Gross?

Claim your profile

Publications (176)901.82 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    Journal of the American College of Nutrition 03/2015; DOI:10.1080/07315724.2014.926155 · 1.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE. To test the hypothesis that tumor necrosis factor (TNF) gene polymorphisms are associated with diabetic retinopathy (DR) in Caucasians with type 2 diabetes mellitus. METHODS. In a case-control study, the -238G>A (rs361525), -308G>A (rs1800629) and -857C>T (rs1799724) polymorphisms of the TNF gene were genotyped in 745 outpatients with type 2 diabetes, including 331 subjects without DR, 246 with nonproliferative DR (NPDR), and 168 with proliferative DR (PDR). RESULTS. Genotype and allele frequencies of the -238G>A, -308G>A and -857C>T polymorphisms in subjects with NPDR were not significantly different from those of subjects without DR (P > 0.05 for all comparisons). However, the A allele of the -308G>A polymorphism was more frequent in subjects with PDR than in those with no DR (18.1% vs. 11.5%, corrected P = 0.035). Multivariate logistic regression analysis showed that the -308A allele was independently associated with an increased risk of PDR, under a dominant model (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.11-2.98). The combined analysis of the three polymorphisms also showed that haplotypes containing the -308A allele were associated with an increased risk of PDR (aOR, 2.36; 95% CI, 1.29-4.32). CONCLUSIONS. This study detected, for the first time, an independent association of the -308G>A polymorphism in the TNF gene with PDR in Caucasian-Brazilians with type 2 diabetes. This finding suggests that TNF is a potential susceptibility gene for PDR. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 01/2015; 56(2). DOI:10.1167/iovs.14-15758 · 3.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine.RESEARCH DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26.RESULTS: At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).CONCLUSIONS: Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.
    Diabetes Care 06/2014; 37(8). DOI:10.2337/dc14-0001 · 8.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Higher intake of dietary fiber is associated with lower risk of coronary heart disease, the leading cause of mortality among people with type 1 diabetes. The protective effect includes the anti-inflammatory properties of some foods. Population-based studies have shown an inverse association between some nutritional habits and high sensitive -C-reactive protein (hs-CRP). This study aimed to ascertain the association between fiber intake and hs-CPR levels in patients with type 1 diabetes. Methods This cross-sectional study was conducted with 106 outpatients with type 1 diabetes; age 40 ± 11 years; diabetes duration of 18 ± 8.8 years. Dietary intake was evaluated by 3-day weighed-diet records. Patients were categorized in 2 groups, according to fiber intake (>20 g/day and <20 g/day). Results The group with fiber intake > 20 g/day had lower hs-CRP levels [median (25th-75th) 0.7 mg/dl (0.4-2.4) vs. 1.9 mg/dl (1.0-4.4); P = 0.002], than the other group. Controlled for HbA1c and energy intake, an inverse relation was observed between hs-CRP levels and total fiber [ß = − 0.030 (SE: 0.0120), P = 0.02], soluble fiber [ß = − 0.078 (SE: 0.0421), P = 0.06] and insoluble fiber [ß = − 0.039 (SE: 0.01761), P = 0.026]. Even, after additional adjustment fibers remained associated with lower hs-CRP levels. Total fibers were stratified in 4 groups: < 10 g/day, from 10 to < 20 g/day, from 20 to 30 g/day and > 30 g/day. Compared to the group who ingested < 10 g/day of total fiber (referent group), the group who consumed > 30 g/d had significantly lower hs-CRP levels [−2.45 mg/L, P = 0.012] independent of the HbA1c values. Conclusions The present study suggests that an increased consumption of dietary fiber > 30 g/day may play a role in reducing inflammation in individuals with type 1 diabetes.
    Diabetology and Metabolic Syndrome 05/2014; 6:66. DOI:10.1186/1758-5996-6-66 · 2.50 Impact Factor
  • Diabetes & Metabolism 03/2014; 40:A107. DOI:10.1016/S1262-3636(14)72629-1 · 2.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment. We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1β, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections. Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1β, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls. Brain death induces inflammation evidenced by the up-regulation of TNF in serum and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.
    Transplantation 10/2013; 97(2). DOI:10.1097/TP.0b013e3182a949fa · 3.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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; beta-adrenergic blocking agent and calcium channel blocking agent if BP >130/80 mmHg. 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. 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.
    Diabetology and Metabolic Syndrome 09/2013; 5(1):52. DOI:10.1186/1758-5996-5-52 · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. Cross-sectional study. 14 centres in five regions of Brazil, including primary care units and outpatient clinics of University Hospitals. Patients with type 2 diabetes attending outpatient clinics of public healthcare system. Glycated haemoglobin (HbA1c), centrally measured by high-performance liquid chromatography (National Glycohemoglobin Standardization Program certified). 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%. 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.
    BMJ Open 09/2013; 3(9):e003336. DOI:10.1136/bmjopen-2013-003336 · 2.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus. Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA1c of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA1c and percentages of patients achieving HbA1c < 53 mmol/mol (< 7.0%) were assessed in study 14. No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA1c decreased with saxagliptin but increased with placebo. Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 06/2013; 30(12). DOI:10.1111/dme.12267 · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aims: The common polymorphism in the FTO gene (rs9939609) has been associated with obesity, type 2 diabetes, and appetite regulation. The aim of this study was to evaluate possible associations of FTO rs9939609 with dietary factors in patients with type 2 diabetes. Methods: This was a cross-sectional study of 236 patients with type 2 diabetes (age 60.0 ± 10.3 years; diabetes duration 12.7 ± 8.2 years; 53.4% females) who were genotyped for FTO rs9939609. Patients underwent clinical and laboratory evaluations and 3-day weighed diet records. Data on dietary intake were categorized as high or low, based on median values. Results: The AA genotype in the FTO gene was positively associated with high fat (>34% energy; OR = 2.17; 95% CI 1.02-4.63) and low fiber intakes (<16 g/day; OR = 2.42; 95% CI 1.05-5.57), adjusted for gender, BMI, total energy intake, systolic blood pressure, and HbA1c. When gender was taken into account, AA females had higher fat (37.4 ± 5.3 vs. 32.6 ± 7.5 and 32.2 ± 6.2% energy; p = 0.005) and lower fiber intakes (12.4 ± 4.4 vs. 15.1 ± 6.3 and 16.7 ± 5.6 g/day; p = 0.023) than patients with TT and AT genotypes. Multiple logistic regression models confirmed female associations for high fat (OR = 9.73; 95% CI 2.12-44.66) and low fiber intakes (OR = 4.28; 95% CI 1.14-16.06; p < 0.05 for all models). Conclusions: Patients with type 2 diabetes, who were carriers of the AA genotype of the FTO rs9939609, had increased fat and decreased fiber consumption, independently of BMI.
    Journal of Nutrigenetics and Nutrigenomics 05/2013; 6(2):97-106. DOI:10.1159/000350741 · 2.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.RESEARCH DESIGN AND METHODS In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from baseline in A1C at 52 weeks. Secondary end points included change in fasting plasma glucose (FPG) and systolic blood pressure (BP), and percent change in body weight, triglycerides, and HDL cholesterol. Safety was assessed based on adverse event (AE) reports.RESULTSAt 52 weeks, canagliflozin 300 mg demonstrated noninferiority and, in a subsequent assessment, showed superiority to sitagliptin 100 mg in reducing A1C (-1.03% [-11.3 mmol/mol] and -0.66% [-7.2 mmol/mol], respectively; least squares mean difference between groups, -0.37% [95% CI, -0.50 to -0.25] or -4.0 mmol/mol [-5.5 to -2.7]). Greater reductions in FPG, body weight, and systolic BP were observed with canagliflozin versus sitagliptin (P < 0.001). Overall AE rates were similar with canagliflozin (76.7%) and sitagliptin (77.5%); incidence of serious AEs and AE-related discontinuations was low for both groups. Higher incidences of genital mycotic infections and osmotic diuresis-related AEs were observed with canagliflozin, which led to one discontinuation. Hypoglycemia rates were similar in both groups.CONCLUSION Findings suggest that canagliflozin may be a new therapeutic tool providing better improvement in glycemic control and body weight reduction than sitagliptin, but with increased genital infections in subjects with type 2 diabetes using metformin plus sulfonylurea.
    Diabetes care 04/2013; 36(9). DOI:10.2337/dc12-2491 · 8.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the association of coronary artery calcium score with all cause mortality and cardiovascular events in people with type 2 diabetes. Systematic review and meta-analysis of observational studies. 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). Two independent reviewers extracted the data. The predictive value of the coronary artery calcium score was assessed by random effects model. 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; I(2)=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; I(2)=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. 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.
    BMJ (online) 03/2013; 346:f1654. DOI:10.1136/bmj.f1654 · 16.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. METHODS: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5, 5, or 10 mg) plus open-label metformin ([greater than or equal to]1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. RESULTS: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5, 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg). CONCLUSIONS: Dapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone. Trial registration: Clinicaltrials.gov NCT00528879.
    BMC Medicine 02/2013; 11(1):43. DOI:10.1186/1741-7015-11-43 · 7.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Diabetology and Metabolic Syndrome 11/2012; 4(1):47. DOI:10.1186/1758-5996-4-47 · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose. Uncoupling protein 1 (UCP1) reduces mitochondrial production of reactive oxygen species (ROS). ROS overproduction is related to diabetic retinopathy (DR), a chronic complication of diabetes mellitus (DM). Therefore, deleterious polymorphisms in UCP1 gene are candidate risk factors for DR. We investigated the relationships between the UCP1 -3826A/G polymorphism and risk of DR and UCP1 gene expression in human retina. Considering that superoxide dismutase-2 (MnSOD2) enzyme is the first line of defence against oxidative stress in mitochondria, we also analyzed MnSOD2 gene expression in retinal samples according to different UCP1 -3826A/G genotypes. Methods. In a case-control study, frequencies of -3826A/G polymorphisms were analyzed in 257 type 1 DM patients (154 cases with DR and 103 controls without DR). In a cross-sectional study comprising cadaveric cornea donors, UCP1 and MnSOD2 gene expressions were evaluated in 107 retinal samples differentiated according to different -3826A/G genotypes. Results. In the type 1 DM group, multivariate analysis confirmed that the G/G genotype was an independent risk factor for DR (OR=3.503; P=0.043). In cornea donors, G allele carriers had higher UCP1 cDNA and protein concentrations than A/A carriers (P=0.034 and P=0.039; respectively). Interestingly, G allele carriers exhibited increased MnSOD2 expression (P=0.001). Conclusions. This study suggests that the -3826A/G polymorphism is associated with DR in type 1 DM patients. This is the first report demonstrating UCP1 gene expression in human retinas and indicates that the -3826A/G polymorphism influences its expression. In addition, the -3826G allele was associated with increased MnSOD2 expression; thus, suggesting that this allele could be a marker of oxidative stress.
    Investigative ophthalmology & visual science 10/2012; 53(12). DOI:10.1167/iovs.12-10660 · 3.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nitric oxide synthesized by endothelial nitric oxide synthase (eNOS) plays a key role in the regulation of endothelial function, and controversial results regarding the association of eNOS gene polymorphisms with diabetic complications have been reported. In this case-control study, the relationship of the -786T/C, the VNTR intron 4 a/b and the 894G/T (Glu298Asp) polymorphisms in the eNOS gene with the presence or severity of diabetic retinopathy was analyzed in 630 Caucasian-Brazilians with type 2 diabetes (434 with and 196 without diabetic retinopathy). Genotyping of eNOS polymorphisms was carried out using the PCR or PCR-RFLP method, and haplotype frequencies were estimated using a Bayesian method. Genotype and allele frequencies in patients with any degree of diabetic retinopathy or proliferative diabetic retinopathy were not significantly different from those of patients without this complication for all eNOS polymorphisms. Likewise, there were no differences in haplotype frequencies among diabetic patients with or without diabetic retinopathy (p values > 0.05 for all comparisons). Our findings do not support the hypothesis that the -786T/C, the VNTR intron 4 a/b and the 894G/T (Glu298Asp) polymorphisms in the eNOS gene play a role in the pathogenesis of diabetic retinopathy in type 2 diabetes.
    Ophthalmic Genetics 03/2012; 33(1):23-7. DOI:10.3109/13816810.2011.620057 · 1.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9%) outpatients and in 34 of 186 (18.7%) dialysis patients. Among HCV+ patients, 32 were men (43.8%). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 µKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 µKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 µKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 µM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7%; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 02/2012; 45(3):284-90. DOI:10.1590/S0100-879X2012007500013 · 1.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been recommended that urinary albumin be measured in sterile urine for the proper diagnosis of diabetic nephropathy. However, the association between bacteriuria and urinary albumin is controversial. A systematic review and meta-analysis was performed to investigate the association of albuminuria and bacteriuria in patients with diabetes. Medline and Embase were searched (beginning in 1950 until November 2010). Data were extracted independently by two investigators. The pooled OR estimates were calculated using the random effects model. We identified 305 studies in the database searches. A total of seven studies were included, providing data from 1,552 patients (mean age 56.4 years). The OR of bacteriuria for the presence of micro- and/or macroalbuminuria was 1.60 (95% CI: 0.97-2.66, I(2) = 66.6%) as compared to patients without bacteriuria. Funnel plots and the Egger regression test suggested no significant asymmetry in the analysis (p = 0.21). In a sensitivity analysis including the five studies (1,197 participants) that evaluated microalbuminuria as the outcome, the OR of bacteriuria for microalbuminuria was 1.22 (95% CI: 0.68-2.19). In conclusion, no association was identified between albuminuria and bacteriuria considering the current literature. Further prospective studies of a large diabetic population are needed to clarify such an association.
    Nephron Clinical Practice 01/2012; 120(1):c54-8. DOI:10.1159/000334770 · 1.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Uncoupling protein 2 (UCP2) is a mitochondrial transporter present in the inner membrane of mitochondria, and it uncouples substrate oxidation from ATP synthesis, thereby dissipating the membrane potential energy and consequently decreasing ATP production by mitochondrial respiratory chain. As a consequence of the uncoupling, UCP2 decreases the reactive oxygen species (ROS) formation by mitochondria. ROS overproduction is related to diabetic retinopathy (DR), a chronic complication of diabetes mellitus (DM). Recently, our group reported that the -866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of the UCP2 gene was associated with increased risk for DR in patients with DM. The purpose of this study was to analyze the effect of this haplotype on UCP2 gene expression in human retina. In addition, MnSOD2 gene expression was also investigated according to different UCP2 haplotypes. This cross-sectional study included 188 cadaveric cornea donors. In a subset of 91 retinal samples differentiated according to the presence of the mutated UCP2 haplotype and risk alleles of the -866G/A and Ins/Del polymorphisms, UCP2 and MnSOD2 gene expressions were measured by semi-quantitative RT-qPCR. Mutated UCP2 haplotype carriers (homozygous + heterozygous) had a lower UCP2 gene expression than reference haplotype carriers (8.4 ± 7.6 vs. 18.8 ± 23.7 arbitrary units; P = 0.046). Accordingly, UCP2 gene expression was decreased in -866A carriers when compared with G/G carriers (P = 0.010). UCP2 gene expression did not differ between Ins allele carriers and Del/Del carriers (P = 0.556). Interestingly, subjects carrying the heterozygous UCP2 haplotype showed increased MnSOD2 gene expression (P = 0.025). This is the first report suggesting that the presence of the -866A/55Val/Ins haplotype is associated with decreased UCP2 gene expression in human retina. Possibly, MnSOD2 expression might influence the UCP2 effect in the protection against oxidative stress.
    Experimental Eye Research 11/2011; 94(1):49-55. DOI:10.1016/j.exer.2011.11.004 · 3.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In patients with type 2 diabetes, the presence of retinopathy is associated with increased cardiovascular disease, regardless of known risk factors for vascular disease. To investigate the association of diabetic retinopathy (DR) and its grades with the presence of subclinical coronary atherosclerosis in patients with type 1 diabetes. A cross-sectional study was conducted with 150 type 1 diabetes individuals asymptomatic for coronary artery disease. They underwent clinical evaluation for microvascular complications and for the presence of coronary artery calcification (CAC). Severe forms of DR (severe non-proliferative DR and proliferative DR) were associated with CAC (OR: 3.98 95% CI 1.13-13.9, p = 0.03), regardless of known risk factors for cardiovascular disease (age, A1C, hypertension, dyslipidemia and male gender). Patients with severe forms of DR are at risk for the presence of coronary artery disease regardless of traditional cardiovascular risk factors.
    Arquivos brasileiros de cardiologia 10/2011; 97(4):346-9. DOI:10.1590/S0066-782X2011005000101 · 1.12 Impact Factor

Publication Stats

3k Citations
901.82 Total Impact Points

Institutions

  • 1987–2015
    • Hospital De Clínicas De Porto Alegre
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 1997–2014
    • Universidade Federal do Rio Grande do Sul
      • • Departamento de Medicina Interna
      • • Departamento de Genética
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 2005
    • Joslin Diabetes Center
      Boston, Massachusetts, United States
  • 2002
    • Universidade de Passo Fundo
      • Faculdade de Medicina
      Passo Fundo, Estado do Rio Grande do Sul, Brazil
  • 1998
    • Universidade Federal de Pelotas
      • School of Nutrition (FN)
      Pelotas, Estado do Rio Grande do Sul, Brazil