13 research outputs found
Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study
Objective
We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).
Research Design and Methods
732 recently diagnosed T2D patients from the IMI-DIRECT study were extensively phenotyped over three years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS) and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.
Results
Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS, and increasing CLIm; visceral or liver fat, HDL-cholesterol and triglycerides had further independent, though weaker, roles (R2=0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from AUROC=0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS and CLIm was relatively stable (odds ratios 0.07 to 0.09). T2D polygenic risk score and baseline pancreatic fat, GLP-1, glucagon, diet, and physical activity did not show an independent role.
Conclusions
Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of T2D patients in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression
A cross-sectional investigation into the occupational and socio-demographic characteristics of British police force employees reporting a dietary pattern associated with cardiometabolic risk: findings from the Airwave Health Monitoring Study
Nutrient profiling and nutritional genomic influence on metabolic risk of cardiovascular diseases and diabetes: The Airwave Health Monitoring Study
Background: Cardiovascular disease (CVD) is one of the leading causes of death worldwide, driven by various metabolic risk factors and diabetes. Diet is a key modifiable component in the development of these risk factors. This study aimed to investigate cardio-metabolic risk factors associated with diet. Secondly, dietary interaction with genetic risk of diabetes.
Methods: A cross-sectional analysis was conducted on 5,864 participants’ baseline data from the Airwave Health Monitoring Study. Participants completed a 7-day food diary and a health screening including blood sample, blood pressure and anthropometrics. Diet quality was assessed according to UK Dietary Reference Values (DRV) using the novel DRV index and the established UK nutrient profile model. The nutritional genomic association with diabetes and HbA1c% was studied using a polygenetic risk score (GRS).
Results: A higher DRV score was associated with a lower waist circumference ( -0.56 p16g/day) modified the genetic effect on HbA1c ( 1.22, p=0.002). Obesity (BMI >30kg/m2) increased the effect on HbA1c by =1.90 pinteraction =0.0006.
Conclusion: Individuals consuming a high quality diet (high in complex carbohydrates, fibre, fruit and vegetables and wholegrain) aligned with the UK guidelines were associated with fewer metabolic risk factors for CVD and diabetes. A high quality diet also reduced the genetic effect on HbA1c and diabetes in high-risk individuals. These findings support the importance of encouraging a healthy diet, along with moderate alcohol consumption, as part of public health advice for a lower risk of CVD and diabetes, especially in high genetic risk groups.Open Acces
Gene-diet quality interactions on HbA1c and type 2 diabetes risk:The Airwave Health Monitoring Study
Introduction: Type 2 Diabetes (T2D) is multi-factorial involving lifestyle, environmental and genetic risk factors. This study aims to investigate the impact of genetic interactions with alcohol and diet quality on glycated haemoglobin A1c (HbA1c) independent of obesity, in a British population. Methods: Cross-sectional study of 14,089 white British participants from Airwave Health Monitoring Study, and a sub-sample of 3,733 participants with dietary data. A T2D genetic risk score (GRS) was constructed and its interactions with diet on HbA1c were assessed. Results: GRS was associated with a higher HbA1c% ( 0.03, p<0.0001) and a higher risk of pre-diabetes (OR 1.09, p<0.0001) and T2D (OR 1.14, p 0.006). The genetic effect on HbA1c% was significantly higher in obese participants ( 1.88, pinteraction 0.03). A high intake of wholegrain attenuated the effect on HbA1c% in high-risk individuals pinteraction 0.04. Conclusion: The genetic effect on HbA1c was almost doubled in obese individuals, compared with those with a healthy weight, and independent of weight there was a modest offset on HbA1c in high-genetic risk individuals consuming a diet high in wholegrain. This supports the importance of a healthy diet high in wholegrains and along with maintaining a healthy weight in controlling HbA1c amongst high genetic risk groups
Nutrient profiling and adherence to components of the UK national dietary guidelines association with metabolic risk factors for CVD and diabetes: Airwave Health Monitoring Study
Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk:An IMI DIRECT study
Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.</p
“The Death of the ‘New Poete’: Virgilian Ruin and Ciceronian Recollection in Spenser’s The Shepheardes Calender
Evaluation of microplastics in Jurujuba Cove, Niterói, RJ, Brazil, an area of mussels farming
Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity
Toll-like receptor 4 (TLR4), which signals through the adapter molecules myeloid differentiation factor 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter inducing IFN-β (TRIF), is required for protection against Gram-negative bacteria. TRIF is known to be important in TLR3-mediated antiviral signaling, but the role of TRIF signaling against Gram-negative enteropathogens is currently unknown. We show that TRIF signaling is indispensable for establishing innate protective immunity against Gram-negative Yersinia enterocolitica. Infection of wild-type mice rapidly induced both IFN-β and IFN-γ in the mesenteric lymph nodes. In contrast, TRIF-deficient mice were defective in these IFN responses and showed impaired phagocytosis in regional macrophages, resulting in greater bacterial dissemination and mortality. TRIF signaling may be universally important for protection against Gram-negative pathogens, as TRIF-deficient macrophages were also impaired in killing both Salmonella and Escherichia coli in vitro. The mechanism of TRIF-mediated protective immunity appears to be orchestrated by macrophage-induced IFN-β and NK cell production of IFN-γ. Sequential induction of IFN-β and IFN-γ leads to amplification of macrophage bactericidal activity sufficient to eliminate the invading pathogens at the intestinal interface. Our results demonstrate a previously unknown role of TRIF in host resistance to Gram-negative enteropathogens, which may lead to effective strategies for combating enteric infections