A mutational signature in gastric cancer suggests therapeutic strategies

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Revisiting clinical trials on glycemic control and cardiovascular risk

The most relevant clinical trials, assessing the role of glycemic control in reducing cardiovascular risk, are examined. The UKPDS was the first to address this issue. More recent trials (ACCORD, ADVANCE and VADT) are controversial and evidences did not support that strict glycemic control (reflected by normal glycated hemoglobin) exclusively is sufficient to reduce cardiovascular risk in complicated individuals with long-term type 2 diabetes mellitus. Some possible reasons for controversies are included

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Ten-Year Mortality and Cardiovascular Morbidity in the Finnish Diabetes Prevention Study—Secondary Analysis of the Randomized Trial

The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states.Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control "mini-intervention" group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21-1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72-1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09-0.52) and 0.39 (95% CI 0.20-0.79) for total mortality, and 0.89 (95% CI 0.62-1.27) and 0.87 (0.60-1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17-0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64-1.21).Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up.ClinicalTrials.gov NCT00518167

Cardiorespiratory fitness predicts clustered cardiometabolic risk in 10-11.9 year olds

The aim of this study was to investigate levels of clustered cardiometabolic risk and the odds of being ‘at risk’ according to cardiorespiratory fitness status in children. Data from 88 10–11.9-year-old children (mean age 11.05 ± 0.51 years), who participated in either the REACH Year 6 or the Benefits of Fitness Circuits for Primary School Populations studies were combined. Waist circumference, systolic blood pressure, diastolic blood pressure, glucose, triglycerides, high-density lipoprotein cholesterol, adiponectin and C-reactive protein were assessed and used to estimate clustered cardiometabolic risk. Participants were classified as ‘fit’ or ‘unfit’ using recently published definitions (46.6 and 41.9 mL/kg/min for boys and girls, respectively), and continuous clustered risk scores between fitness groups were assessed. Participants were subsequently assigned to a ‘normal’ or ‘high’ clustered cardiometabolic risk group based on risk scores, and logistic regression analysis assessed the odds of belonging to the increased cardiometabolic risk group according to fitness. The unfit group exhibited significantly higher clustered cardiometabolic risk scores (p < 0.001) than the fit group. A clear association between fitness group and being at increased cardiometabolic risk (B = 2.509, p = 0.001) was also identified, and participants classed as being unfit were found to have odds of being classified as ‘at risk’ of 12.30 (95 % CI = 2.64–57.33).\ud \ud Conclusion Assessing cardiorespiratory fitness is a valid method of identifying children most at risk of cardiometabolic pathologies. The ROC thresholds could be used to identify populations of children most at risk and may therefore be used to effectively target a cardiometabolic risk-reducing public health intervention

Clinical characteristics of patients with type 2 diabetes mellitus at the time of insulin initiation: INSTIGATE observational study in Spain

Little information is available on the management of patients with type 2 diabetes mellitus (DM2) in regular clinical practice, prior to and at the point of initiating treatment with insulin. The INSTIGATE study provides a description of the clinical profile of the patient with DM2 who begins treatment with insulin in both primary and secondary care. A total of 224 patients who had been diagnosed with DM2, were not responding to oral treatment, and began receiving insulin were included in the INSTIGATE study in Spain. Demographic data were collected, as well as data on macro- and microvascular complications of diabetes and comorbidities, past medical history of diabetes and oral treatment administered, the clinical severity of diabetes (HbA1c concentration) and insulin treatment initiated. Mean age of the sample was 65.4 years and 56.7% were men. There were 87% of patients who had a diagnosis of at least one significant comorbidity, notably hypertension and hyperlipidemia. The patient profile for metabolic syndrome was met by 75.1% of the patients. There was a higher incidence of macrovascular complications (38.4%) than microvascular complications (16.1%). Prior to insulin initiation, the most recent mean HbA1c was 9.2%. The majority of patients had been treated in the last 12 months with sulfonylureas and/or metformin (69.6 and 57.6%). The most common treatment prior to insulinization was the co-administration of two oral antidiabetics (OADs) (37.5%). Patients with DM2 observed in the study presented with elevated mean HbA1c and body mass index levels, comorbidities and complications related to diabetes at the time of insulin initiation. Changes and adjustments in treatment from diagnosis of diabetes occur when HbA1c levels are far above those recommended by the IDF (International Diabetes Federation), a factor which could be contributing to the development of both macrovascular and microvascular complications in the patient profile described in the study

Collaborative denoising autoencoder for high glycated haemoglobin prediction.

A pioneering study is presented demonstrating that the presence of high glycated haemoglobin (HbA1c) levels in a patient’s blood can be reliably predicted from routinely collected clinical data. This paves the way for performing early detection of Type-2 Diabetes Mellitus (T2DM). This will save healthcare providers a major cost associated with the administration and assessment of clinical tests for HbA1c. A novel collaborative denoising autoencoder framework is used to address this challenge. The framework builds an independent denoising autoencoder model for the high and low HbA1c level, which extracts feature representations in the latent space. A baseline model using just three features: patient age together with triglycerides and glucose level achieves 76% F1-score with an SVM classifier. The collaborative denoising autoencoder uses 78 features and can predict HbA1c level with 81% F1-score

Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer

Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer

Younger adult type 2 diabetic patients have poorer glycaemic control: A cross-sectional study in a primary care setting in Singapore

10.1186/1472-6823-13-18BMC Endocrine Disorders13-BEDM