Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes mellitus

Background Metabolic syndrome refers to risk factors for cardiovascular disease. Hyperglycemia is a critical component contributing to the predictive power of the syndrome. This study aimed to evaluate the results from the laparoscopic interposition of an ileum segment into the proximal jejunum for the treatment of metabolic syndrome in patients with type 2 diabetes mellitus and a body mass index (BMI) lower than 35. Methods Laparoscopic procedures were performed for 60 patients (24 women and 36 men) with a mean age of 51.7 +/- 6.4 years (range, 27-66 years) and a mean BMI of 30.1 +/- 2.7 (range, 23.6-34.4). All the patients had a diagnosis of type 2 diabetes mellitus (T2DM) given at least 3 years previously and evidence of stable treatment using oral hypoglycemic agents, insulin, or both for at least 12 months. The mean duration of type 2 diabetes mellitus was 9.6 +/- 4.6 years (range, 3-22 years). Metabolic syndrome was diagnosed for all 60 patients. Arterial hypertension was diagnosed for 70% of the patients (mean number of drugs, 1.6) and hypertriglyceridemia for 70%. High-density lipoprotein was altered in 51.7% of the patients and the abdominal circumference in 68.3%. Two techniques were performed: ileal interposition (II) into the proximal jejunum and sleeve gastrectomy (II-SG) or ileal interposition associated with a diverted sleeve gastrectomy (II-DSG). Results The II-SG procedure was performed for 32 patients and the II-DSG procedure for 28 patients. The mean postoperative follow-up period was 7.4 months (range, 3-19 months). The mean BMI was 23.8 +/- 4.1 kg/m(2), and 52 patients (86.7%) achieved adequate glycemic control. Hypertriglyceridemia was normalized for 81.7% of the patients. An high-density lipoprotein level higher than 40 for the men and higher than 50 for the women was achieved by 90.3% of the patients. The abdominal circumference reached was less than 102 cm for the men and 88 cm for the women. Arterial hypertension was controlled in 90.5% of the patients. For the control of metabolic syndrome, II-DSG was the more effective procedure. Conclusions Laparoscopic II-SG and II-DSG seem to be promising procedures for the control of the metabolic syndrome and type 2 diabetes mellitus. A longer follow-up period is needed.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Derivation and external validation of a simple prediction model for the diagnosis of type 2 Diabetes Mellitus in the Brazilian urban population

A risk score model was developed based in a population of 1,224 individuals from the general population without known diabetes aging 35 years or more from an urban Brazilian population sample in order to select individuals who should be screened in subsequent testing and improve the efficacy of public health assurance. External validation was performed in a second, independent, population from a different city ascertained through a similar epidemiological protocol. The risk score was developed by multiple logistic regression and model performance and cutoff values were derived from a receiver operating characteristic curve. Model`s capacity of predicting fasting blood glucose levels was tested analyzing data from a 5-year follow-up protocol conducted in the general population. Items independently and significantly associated with diabetes were age, BMI and known hypertension. Sensitivity, specificity and proportion of further testing necessary for the best cutoff value were 75.9, 66.9 and 37.2%, respectively. External validation confirmed the model`s adequacy (AUC equal to 0.72). Finally, model score was also capable of predicting fasting blood glucose progression in non-diabetic individuals in a 5-year follow-up period. In conclusion, this simple diabetes risk score was able to identify individuals with an increased likelihood of having diabetes and it can be used to stratify subpopulations in which performing of subsequent tests is necessary and probably cost-effective.

Effects of Optimal Medical Treatment With or Without Coronary Revascularization on Angina and Subsequent Revascularizations in Patients With Type 2 Diabetes Mellitus and Stable Ischemic Heart Disease

Background-In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations. Methods and Results-Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%; P < 0.001), new angina (37% versus 51%; P = 0.001), and subsequent coronary revascularizations (18% versus 33%; P < 0.001) and a higher rate of angina-free status (66% versus 58%; P = 0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV. Conclusions-In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study

Background and Aim: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. Methods and Results: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n = 833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n = 36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n = 21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). Conclusions: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes. (C) 2009 Elsevier B.V. All rights reserved.

Aerobic exercise training improves the role of high-density lipoprotein antioxidant and reduces plasma lipid peroxidation in type 2 diabetes mellitus

In this study, we analyzed the effect of aerobic exercise training (AET) and of a single bout of exercise on plasma oxidative stress and on antioxidant defenses in type 2 diabetes mellitus (DM) and in healthy control subjects (C). DM and C did not differ regarding triglycerides, high-density lipoprotein cholesterol (HDL-c), insulin, and HOMA index at baseline and after AET. To measure the lag time for low-density lipoprotein (LDL) oxidation (LAG) and the maximal rate of conjugated diene formation (MCD), participants` plasma HDL(2) and HDL(3) were incubated with LDL from pooled healthy donors` plasma. In the presence of HDL(3), both LAG and MCD were similar in C and DM, but only in DM did AET improve LAG and reduce MCD. In the presence of HDL(2), the lower baseline LAG in DM equaled C after AET. MCD was unchanged in DM after AET, but was lower than C only after AET. Furthermore, after AET plasma thiobarbituric acid-reactive substances were reduced only in DM subjects. Despite not modifying the total plasma antioxidant status and serum paraoxonase-1 activity in both groups, AET lowered the plasma lipid peroxides, corrected the HDL(2), and improved the HDL(3) antioxidant efficiency in DM independent of the changes in blood glucose, insulin, and plasma HDL concentration and composition.

Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus

Background Peridural blockade with lidocaine, bupivacaine, and fentanyl is an anesthetic procedure extensively used in obstetrics, justifying the pharmacokinetic study of these drugs during labor. Objective To investigate the influence of the physiopathological changes of gestational diabetes mellitus (GDM) on the pharmacokinetics of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women subjected to peridural anesthesia. Patients and methods Ten normal pregnant women (group 1) and six pregnant women with GDM (group 2) were studied, all of them at term. The patients received 200 mg 2% lidocaine hydrochloride without a vasoconstrictor by the peridural locoregional route. Maternal blood samples were collected at predetermined times for the analysis of lidocaine and MEGX by chromatography and pharmacokinetic analysis. Results The median pharmacokinetic parameters of lidocaine for groups 1 and 2 (P <= 0.05), respectively, were as follows: for Cmax 879.11 and 1,145.58 ng/ml, AUC(0-infinity) 256.01 and 455.95 wg min(-1) ml(-1), Cl/f/kg 10.61 and 5.64 ml min(-1) kg(-1), and Vd/f/kg 3.26 and 2.19 L/kg. The median pharmacokinetic parameters of MEGX for groups 1 and 2 (P <= 0.05), respectively, were as follows: for Cmax 82.71 and 141.38 ng/ml, Tmax 44.71 and 193.14 min, t(1/2)alpha 7.64 and 59.77 min, alpha 0.097 and 0.012/min, and AUC(0-infinity) 29.91 and 108.23 mu g min(-1) ml(-1). Conclusion The present data permit us to conclude that the apparent clearance of lidocaine and MEGX was reduced in diabetic patients compared to normal women, suggesting that GDM inhibits the CYP1A2/CYP3A4 isoforms responsible for the metabolism of this drug and its metabolite.

Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1)

Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed ""promiscuous gene expression"" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

Diet, lifestyle and the risk of Type 2 Diabetes Mellitus in women

Background Previous studies have examined individual dietary and lifestyle factors in relation to type 2 diabetes, but the combined effects of these factors are largely unknown. Methods We followed 84,941 female nurses from 1980 to 1996; these women were free of diagnosed cardiovascular disease, diabetes, and cancer at base line. Information about their diet and lifestyle was updated periodically. A low-risk group was defined according to a combination of five variables: a body-mass index (the weight in kilograms divided by the square of the height in meters) of less than 25; a diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load (which reflects the effect of diet on the blood glucose level); engagement in moderate-to-vigorous physical activity for at least half an hour per day; no current smoking; and the consumption of an average of at least half a drink of an alcoholic beverage per day. Results During 16 years of follow-up, we documented 3300 new cases of type 2 diabetes. Overweight or obesity was the single most important predictor of diabetes. Lack of exercise, a poor diet, current smoking, and abstinence from alcohol use were all associated with a significantly increased risk of diabetes, even after adjustment for the body-mass index. As compared with the rest of the cohort, women in the low-risk group (3.4 percent of the women) had a relative risk of diabetes of 0.09 (95 percent confidence interval, 0.05 to 0.17). A total of 91 percent of the cases of diabetes in this cohort (95 percent confidence interval, 83 to 95 percent) could be attributed to habits and forms of behavior that did not conform to the low-risk pattern. Conclusions Our findings support the hypothesis that the majority of cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle.

X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy

To determine whether human X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome (IPEX; MIM 304930) is the genetic equivalent of the scurfy (sf) mouse, we sequenced the human ortholog (FOXP3) of the gene mutated in scurfy mice (Foxp3), in IPEX patients. We found four non-polymorphic mutations. Each mutation affects the forkhead/winged-helix domain of the scurfin protein, indicating that the mutations may disrupt critical DNA interactions.

A diabetes mellitus como determinante em saúde e envelhecimento: o conhecimento do diabético e a presença de complicações da doença

RESUMO: O aumento da longevidade humana é um facto prevalente na actualidade mas, a requerer grandes esforços na promoção da saúde e prevenção de doenças, estando, ainda, as pessoas idosas sob riscos elevados de desenvolver doenças à medida que envelhecem. Assim, é importante o contributo dos próprios indivíduos no sentido minorar estes riscos e retardar a evolução e agudizações das doenças uma vez manifestadas. Nesse sentido, o objectivo geral deste estudo é descrever de que modo os conhecimentos do diabético, podem estar relacionados com a presença de complicações da doença. Realizámos um estudo exploratório descritivo, no Hospital Nossa Senhora do Rosário E.P.E, em pessoas idosas residentes no concelho do Barreiro que frequentaram o Hospital Dia de Diabetologia, após as consultas médicas e de enfermagem. O método utilizado para a selecção da amostra foi a amostragem não probabilística por conveniência (n=50). O instrumento utilizado na colheita de dados foi um questionário, aplicado sob a forma de inquérito, para colheita de dados sócio-demográficos, saúde em geral, estado mental, dados sobre a diabetes e comorbilidades. Os dados foram tratados informaticamente, recorrendo ao programa estatístico S.P.S.S. e a análise de conteúdo. Os resultados obtidos demonstraram que os participantes possuíam conhecimentos sobre a sua doença. Verificámos que os inquiridos que já tiveram complicações devido à diabetes responderam correctamente à questão acerca da medicação ser mais importante que a dieta e o exercício físico para controlar a diabetes, do que os que nunca tiveram complicações devido à diabetes, que responderam incorrectamente ou desconheciam a resposta à questão.----------- ABSTRACT: The increase in human longevity is a fact prevalent nowadays, but to require great efforts on health promotion and disease prevention and is also in the elderly high risk of developing illnesses as they age. It is therefore important contribution of the individuals themselves towards mitigating these risks and delaying the development and exacerbations of disease once manifested. Thus, the general purpose of this study is to describe how the knowledge of diabetes, may be related to complications of the disease. We conducted an exploratory study in the Hospital Nossa Senhora do Rosario EPE, in elderly people living in the county of Barry, who attended the hospital Diabetes Day, after the medical and nursing care. The method used for the sampling was not probabilistic by convenience sampling (n = 50). The instrument used for data collection was a questionnaire applied in the form of survey to collect socio-demographic data, general health, mental state, data on diabetes and comorbidities. The data were processed by computer, using the SPSS and content analysis. The results showed that participants had knowledge about their disease. We found that respondents who have had complications due to diabetes responded correctly to questions about the medication is more important than diet and exercise to control diabetes than those who never had complications due to diabetes, who answered incorrectly or did not know the answer the question.