Daisy Crispim

Prevalência de complicações micro e macrovasculares e de seus fatores de risco em pacientes com diabetes melito do tipo 2 em atendimento ambulatorial

BACKGROUND: Type 2 diabetes (DM2) has been related to the development of macroangiopatic [coronary heart disease (CHD), peripheral vascular disease (PVD) and stroke] and microangiopatic [retinopathy, nephropathy, and distal sensory neuropathy (DSN)] complications. The aims of this study were to analyze prevalence of complications in DM2 patients and to estimate their associated risk factors. METHODS: Cross-sectional study, including 927 out patients with DM2 from three medical centers in Rio Grande do Sul: Hospital de Clinicas de Porto Alegre (n = 475), Grupo Hospitalar Conceicao (n = 229) and Hospital Sao Vicente de Paula (n = 223). Of the patients 42% were male, mean age was 59 ± 10 years and the median known duration of DM2 was 11 (5 - 43) years. Retinopathy was identified by direct fundoscopy; CHD by WHO questionnaire and/or abnormal ECG and/or perfusion abnormalities on myocardial scintigraphy; DSN by compatible symptoms and absent sensation on 10 g monofilament and/or tune fork; PVD by the presence of claudication and absent foot pulses; stroke by presence of sequels and history; and nephropathy by the urinary albumin excretion rate (>20 µg/min). Hypertension was defined by blood pressure (>140/90 mmHg) and/or use of antihypertensive drugs. Body mass index (BMI, kg/m2) and waist-to-hip ratio (WHR) were calculated. RESULTS: CHD was present in 36% and PVD in 33% of the patients. Among the microvascular, 37% had nephropathy (12% with macroalbuminuria); 48% retinopathy (15% proliferative retinopathy). DSN was present in 36%. Seventy three percent of the patients presented arterial hypertension. Cholesterol levels were >200 mg/dl in 64% and BMI > 30 kg/m2 in 36%. Twenty two percent of patients were smokers and 21% ex-smokers. CONCLUSION: Diabetic complications are frequent among out patients referring to general hospitals. Almost all patients presented at least one risk factor for cardiovascular disease, justifying the efforts for identification and adequate control.

Management of the Brain-Dead Organ Donor: A Systematic Review and Meta-Analysis

Background The shortage of organs is a limitation for transplantation, making the care of potential organ donors an important issue. The present systematic review and meta-analysis was carried out to assess the efficacy of interventions to stabilize hemodynamics in brain-dead donors or to improve organ function and outcomes of transplantation. Methods Medline, Embase, and Cochrane databases were searched. Of 5096 articles retrieved, 39 randomized controlled trials were selected. Twenty were included in a qualitative synthesis, providing data on 1277 patients. The main interventions described were desmopressin use, triiodothyronine and methylprednisolone replacement, fluid management, vasopressor therapy, mechanical ventilation strategies, and surgical techniques. Results Three meta-analyses were conducted: the first included two studies and showed that desmopressin administered to brain-dead patients was not advantageous with respect to early organ function in kidney recipients (relative risk, 0.97; 95% confidence interval [CI], 0.85–1.10; I2=0%; P=0.809). The second included four studies and showed that triiodothyronine did not add hemodynamic benefits versus standard management (weighted mean difference, 0.15; 95% CI, −0.13 to 0.42; I2=17.4%; P=0.304). The third meta-analysis (two studies) showed that ischemic liver preconditioning during harvesting procedures did not benefit survival (relative risk, 1.0; 95% CI, 0.93–1.08; I2=0%; P=0.459). Conclusion The present results suggest limited efficacy of interventions focusing on the management of brain-dead donors.

The European-Specific Mitochondrial Cluster J/T Could Confer an Increased Risk of Insulin-Resistance and Type 2 Diabetes: An Analysis of the m.4216T > C and m.4917A > G Variants

The aims of this study were to investigate the contributions of the mitochondrial DNA m.4216T > C and m.4917A > G variants, and also of the European‐specific mitochondrial cluster J/T, to the development of type 2 diabetes mellitus in Caucasian‐Brazilian patients from Southern Brazil. We analyzed 347 type 2 diabetes patients and 350 control subjects. Variant frequencies in patients and control subjects were compared using χ2 tests or odds ratio. We also compared clinical and laboratory characteristics among patients with and without the variants. We found that the frequencies of the m.4216T > C and m.4917A > G variants are higher in diabetic patients than in control subjects. Moreover, haplogroups J (partially defined by the presence of the m.4216T > C variant only) and T (partially defined by the presence of both m.4216T > C and m.4917A > G variants) are more frequent in the type 2 diabetic group than in the control group. Patients belonging to the cluster J/T are more insulin resistant than patients of other haplogroups. In conclusion, our results indicate the association of the cluster J/T (as suggested by analyses of the m.4216T > C and m.4917A > G variants) with insulin resistance and type 2 diabetes.

The role of uncoupling protein 2 (UCP2) on the development of type 2 diabetes mellitus and its chronic complications

It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.

The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

Meta-Analysis Reveals the Association of Common Variants in the Uncoupling Protein (UCP) 1–3 Genes with Body Mass Index Variability

Background The relationship between uncoupling protein (UCP) 1–3 polymorphisms and susceptibility to obesity has been investigated in several genetic studies. However, the impact of these polymorphisms on obesity is still under debate, with contradictory results being reported. Until this date, no meta-analysis evaluated the association of UCP polymorphisms with body mass index (BMI) variability. Thus, this paper describe a meta-analysis conducted to evaluate if the -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3) polymorphisms are associated with BMI changes. Methods A literature search was run to identify all studies that investigated associations between UCP1-3 polymorphisms and BMI. Weighted mean differences (WMD) were calculated for different inheritance models. Results Fifty-six studies were eligible for inclusion in the meta-analysis. Meta-analysis results showed that UCP2 55Val/Val genotype was associated with increased BMI in Europeans [Random Effect Model (REM) WMD 0.81, 95% CI 0.20, 1.41]. Moreover, the UCP2 Ins allele and UCP3-55T/T genotype were associated with increased BMI in Asians [REM WMD 0.46, 95% CI 0.09, 0.83 and Fixed Effect Model (FEM) WMD 1.63, 95% CI 0.25, 3.01]. However, a decreased BMI mean was observed for the UCP2-866 A allele in Europeans under a dominant model of inheritance (REM WMD −0.18, 95% CI −0.35, −0.01). There was no significant association of the UCP1-3826A/G polymorphism with BMI mean differences. Conclusions The meta-analysis detected a significant association between the UCP2-866G/A, Ins/Del, Ala55Val and UCP3-55C/T polymorphisms and BMI mean differences.

Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T Polymorphisms and Susceptibility to Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis

Background Some studies have reported associations between five uncoupling protein (UCP) 1–3 polymorphisms and type 2 diabetes mellitus (T2DM). However, other studies have failed to confirm the associations. This paper describes a case-control study and a meta-analysis conducted to attempt to determine whether the following polymorphisms are associated with T2DM: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3). Methods The case-control study enrolled 981 T2DM patients and 534 nondiabetic subjects, all of European ancestry. A literature search was run to identify all studies that investigated associations between UCP1–3 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast, additive, recessive, dominant and co-dominant inheritance models. Sensitivity analyses were performed after stratification by ethnicity. Results In the case-control study the frequencies of the UCP polymorphisms did not differ significantly between T2DM and nondiabetic groups (P>0.05). Twenty-three studies were eligible for the meta-analysis. Meta-analysis results showed that the Ala55Val polymorphism was associated with T2DM under a dominant model (OR = 1.27, 95% CI 1.03–1.57); while the -55C/T polymorphism was associated with this disease in almost all genetic models: allele contrast (OR = 1.17, 95% CI 1.02–1.34), additive (OR = 1.32, 95% CI 1.01–1.72) and dominant (OR = 1.18, 95% CI 1.02–1.37). However, after stratification by ethnicity, the UCP2 55Val and UCP3 -55C/T alleles remained associated with T2DM only in Asians (OR = 1.25, 95% CI 1.02–1.51 and OR = 1.22, 95% CI 1.04–1.44, respectively; allele contrast model). No significant association of the -3826A/G, -866G/A and Ins/Del polymorphisms with T2DM was observed. Conclusions In our case-control study of people with European ancestry we were not able to demonstrate any association between the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.

The UCP1 −3826A/G Polymorphism Is Associated with Diabetic Retinopathy and Increased UCP1 and MnSOD2 Gene Expression in Human Retina

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 the 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 defense 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.

Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus

Background and objective  Uncoupling protein 2 (UCP2) plays a role in controlling reactive oxygen species (ROS) production by mitochondria. As ROS overproduction is related to diabetic retinopathy (DR), UCP2 gene polymorphisms might be involved in the development of this complication. We investigated whether the −866G/A (rs659366), Ala55Val (rs660339) and 45 bp insertion/deletion (Ins/Del) polymorphisms in the UCP2 gene might be associated with proliferative DR (PDR).

Familial history of type 2 diabetes in patients from Southern Brazil and its influence on the clinical characteristics of this disease

OBJECTIVE To investigate the presence of maternal and paternal history of type 2 diabetes mellitus (DM) in relatives of 644 type 2 diabetic patients from Southern Brazil, and also to evaluate its influence on the clinical characteristics of this disease. PATIENTS AND METHODS Familial history of type 2 DM was investigated by a questionnaire. The maternal and paternal history was investigated over two generations. Complete data sets on familial history were obtained from 396 patients. RESULTS In general, 76.6% of the patients reported at least one first-degree affected relative. Besides, 31.6% of the patients reported a maternal history of type 2 DM and 12.6% reported a paternal history. Patients with maternal and/or paternal history presented a lower age at type 2 DM diagnosis when compared to patients without familial history. In addition, patients with only paternal history presented a higher frequency of hypertension than patients with no familial history. CONCLUSIONS This study suggests that there is a significant maternal effect in the transmission of type 2 DM in Southern Brazil, and that most of the clinical characteristics of this disease do not differ between patients with or without familial history of type 2 DM.