André Gustavo P. Sousa

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR  = 2.32 95%CI 1.27–4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. Clinical Trial Registration Information Medicine, Angioplasty, or Surgery Study (MASS II): Unique identifier: ISRCTN66068876.

Association between genetics of diabetes, coronary artery disease, and macrovascular complications: exploring a common ground hypothesis.

Type 2 diabetes and coronary artery disease (CAD) are conditions that cause a substantial public health burden. Since both conditions often coexist in the same individual, it has been hypothesized that they have a common effector. Insulin and hyperglycemia are assumed to play critical roles in this scenario. In recent years, many genetic risk factors for both diabetes and CAD have been discovered, mainly through genome-wide association studies. Genetic aspects of diabetes, diabetic macrovascular complications, and CAD are assumed to have intersections leading to the common effector hypothesis. However, only a few genetic risk factors could be identified that modulate the risk for both conditions. Polymorphisms in TCF7L2 and near the CDKN2A/B genes seem to be of great importance in this regard since they appear to modulate both conditions, and they are not necessarily related to insulinism, or hyperglycemia, for CAD development. Other issues related to this hypothesis, such as the problems of phenotype heterogeneity, are also of interest. Recent studies have contributed to a better understanding of the complex genetics of diabetic macrovascular complications. Much effort is still needed to clarify the associations in the genetics of diabetes, and cardiovascular disease. At present, there is little genetic evidence to support a common effector hypothesis, other than insulin or hyperglycemia, for the association between these conditions.

General aspects of muscle glucose uptake

Glucose uptake in peripheral tissues is dependent on the translocation of GLUT4 glucose transporters to the plasma membrane. Studies have shown the existence of two major signaling pathways that lead to the translocation of GLUT4. The first, and widely investigated, is the insulin activated signaling pathway through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The second is the insulin-independent signaling pathway, which is activated by contractions. Individuals with type 2 diabetes mellitus have reduced insulin-stimulated glucose uptake in skeletal muscle due to the phenomenon of insulin resistance. However, those individuals have normal glucose uptake during exercise. In this context, physical exercise is one of the most important interventions that stimulates glucose uptake by insulin-independent pathways, and the main molecules involved are adenosine monophosphate-activated protein kinase, nitric oxide, bradykinin, AKT, reactive oxygen species and calcium. In this review, our main aims were to highlight the different glucose uptake pathways and to report the effects of physical exercise, diet and drugs on their functioning. Lastly, with the better understanding of these pathways, it would be possible to assess, exactly and molecularly, the importance of physical exercise and diet on glucose homeostasis. Furthermore, it would be possible to assess the action of drugs that might optimize glucose uptake and consequently be an important step in controlling the blood glucose levels in diabetic patients, in addition to being important to clarify some pathways that justify the development of drugs capable of mimicking the contraction pathway.

Predicting malignant involvement in a thyroid nodule: role of ultrasonography.

OBJECTIVE To assess how ultrasonography can contribute during the evaluation of a thyroid nodule and whether this technique can have a role in predicting malignant involvement. METHODS In this retrospective study, data were analyzed on 220 consecutive patients (with 348 thyroid nodules) who underwent thyroidectomy and had previously undergone assessment by high-resolution thyroid ultrasonography. Nodule size, echogenicity, regularity of margins, halo sign, presence or absence of calcifications, and invasion of surrounding tissues were evaluated. The nodules were classified as low, medium, or high risk for malignant involvement on the basis of nodule characteristics found on ultrasonography. All nodules were submitted to cytologic examination by fine-needle aspiration (FNA) before thyroidectomy. Ultrasound, FNA, and pathologic postoperative results were compared. RESULTS Among the 348 thyroid nodules, 56 were ultrasonographically classified as low risk, 268 as medium risk, and 24 as high risk for malignant potential. Fifty of 56 (89.3%) low-risk nodules and 213 of 268 (79.5%) medium-risk nodules were diagnosed as benign at pathologic postoperative examination. In contrast, however, only 6 of 24 (25%) high-risk nodules were diagnosed as benign. Among the 18 high-risk nodules of 1-cm diameter or larger, FNA showed a 20% false-negative result. CONCLUSION High-risk classification of a thyroid nodule on ultrasonography had a positive predictive value for malignant involvement of 75%. Nodule characteristics analyzed by ultrasonography should be considered at the time of surgical intervention.

Dislipidemia pós-prandial como achado precoce em indivíduos com baixo risco cardiovascular

OBJECTIVE: to show a correlation between postprandial hypertriglyceridemia and cardiovascular risk factors to atherogenesis. RESEARCH DESIGN AND METHODS: 47 (30 women and 17 men, 40.5 ± 14.9years, body mass index: 26.1 ± 5.4kg/m2) non diabetic volunteers with normal (<200mg/dl) triglycerides were studied. Triglycerides, HDL-cholesterol and total cholesterol were measured before (basal), 3 and 5 hours after a 70g-lipid standardized test meal. RESULTS: patients with 3 hours postprandial hypertriglycerides higher than the 2nd Quartile (164.8mg/dl), in spite of normal fasting triglycerides, have higher BMI (28.1 ± 5.6 vs. 24.2 ± 4.5kg/m2; p= 0.008), abdominal circumference (95.7 vs. 84.1cm; p= 0.001), waist/hip ratio (0.92 vs. 0.86; p= 0.008) and diastolic pressure (83.1 vs. 77.2mmHg; p= 0.02) and lower HDL (39.1 vs. 48.3mg/dl; p= 0.008). CONCLUSIONS: Postprandial hypertriglyceridemia related well with others risk factors, even in patients with normal fasting triglycerides.

Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.

Objective To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease. Clinical Trial Registration Information Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.

Continuous glucose monitoring system: dawn period calibration does not change accuracy of the method

INTRODUCTION Continuous glucose monitoring system is a valuable instrument to measure glycemic control, which uses a retrospective calibration based upon 3 to 4 capillary glucose meter values inserted by the patient each day. OBJECTIVE We evaluated the interference of calibration during the dawn period in the system accuracy. METHODS The monitoring data were retrospectively divided into two groups: with (Group A) or without (Group B) the dawn period calibration (between 1:00 and 5:00 AM). Accuracy of the method was expressed by relative absolute difference. RESULTS Thirty-four continuous glucose monitoring data were evaluated comprising a total of 112 nights. A total of 289 paired readings were analyzed - 195 in Group A and 94 in Group B. We did not find a difference in relative absolute difference (RAD%) in any analyzed period of day by adding dawn calibration. CONCLUSIONS These data suggest that dawn calibration does not alter accuracy of method.