Diabetes mellitus correlates with increased biological age as indicated by clinical biomarkers

Chronological age (CA) is determined by time of birth, whereas biological age (BA) is based on changes on a cellular level and strongly correlates with morbidity, mortality, and longevity. Type 2 diabetes (T2D) associates with increased morbidity and mortality; thus, we hypothesized that BA would be increased and calculated it from biomarkers collected at routine clinical visits. Deidentified data was obtained from three cohorts of patients (20-80 years old)-T2D, type 1 diabetes (T1D), and prediabetes-and compared to gender- and age-matched non-diabetics. Eight clinical biomarkers that correlated with CA in people without diabetes were used to calculate BA using the Klemera and Doubal method 1 (KDM1) and multiple linear regression (MLR). The phenotypic age (PhAge) formula was used with its predetermined biomarkers. BA of people with T2D was, on average, 12.02 years higher than people without diabetes (p \u3c 0.0001), while BA in T1D was 16.32 years higher (p \u3c 0.0001). Results were corroborated using MLR and PhAge. The biomarkers with the strongest correlation to increased BA in T2D using KDM were A1c (R2 = 0.23, p \u3c 0.0001) and systolic blood pressure (R2 = 0.21, p \u3c 0.0001). BMI had a positive correlation to BA in non-diabetes subjects but disappeared in those with diabetes. Mortality data using the ACCORD trial was used to validate our results and showed a significant correlation between higher BA and decreased survival. In conclusion, BA is increased in people with diabetes, irrespective of pathophysiology, and to a lesser extent in prediabetes

Heterogeneity of increased biological age in type 2 diabetes correlates with differential tissue DNA methylation, biological variables, and pharmacological treatments

Biological age (BA) closely depicts age-related changes at a cellular level. Type 2 diabetes mellitus (T2D) accelerates BA when calculated using clinical biomarkers, but there is a large spread in the magnitude of individuals\u27 age acceleration in T2D suggesting additional factors contributing to BA. Additionally, it is unknown whether BA can be changed with treatment. We hypothesized that potential determinants of the heterogeneous BA distribution in T2D could be due to differential tissue aging as reflected at the DNA methylation (DNAm) level, or biological variables and their respective therapeutic treatments. Publicly available DNAm samples were obtained to calculate BA using the DNAm phenotypic age (DNAmPhenoAge) algorithm. DNAmPhenoAge showed age acceleration in T2D samples of whole blood, pancreatic islets, and liver, but not in adipose tissue or skeletal muscle. Analysis of genes associated with differentially methylated CpG sites found a significant correlation between eight individual CpG methylation sites and gene expression. Clinical biomarkers from participants in the NHANES 2017-2018 and ACCORD cohorts were used to calculate BA using the Klemera and Doubal (KDM) method. Cardiovascular and glycemic biomarkers associated with increased BA while intensive blood pressure and glycemic management reduced BA to CA levels, demonstrating that accelerated BA can be restored in the setting of T2D

Ethnic Disparities in Metabolic Syndrome Among Caregivers of Preschool Children in a Community-Based Trial

American Heart Association Scientific Congress 2017. Anaheim, USA. November 11-15, 2017.Introduction: Obesity and dyslipidemia are increasingly prevalent, disproportionately affecting low-income families. We studied the presence of metabolic syndrome (MetS) by ethnicity among caregivers of preschool children in Harlem, New York. Methods: We analyzed 553 Hispanic and non-Hispanic black caregivers of children in Head Start preschools at their baseline assessment enrolling in a community-based lifestyle intervention. MetS was defined by at least 3 of the following: waist circumference >102/88 cm for men/women respectively, systolic/diastolic blood pressure ≥130/85 mm Hg, serum glucose > 100 mg/dL, triglycerides >150 mg/dL, or HDL < 40/50 mg/dL for men/women. Univariate logistic regression was used to determine significant predictors of MetS, and a multivariable logistic regression model was constructed to predict MetS among participants. Results: The mean age of participants was 37.5±11.3 years old. 34.4% Hispanic and 24.6% non-Hispanic black participants had MetS (p=0.015). This difference in the odds of MetS was primarily driven by a higher incidence of elevated triglycerides, elevated glucose, and low HDL in Hispanic participants, whereas hypertension was more common among black participants. Non-metabolic predictors of MetS in this population included age (OR 1.89 for every 10-year increase in age, p<0.0001, 95% CI: 1.58-2.26), education level (some college or more as compared to high school or less, OR 0.65, p=0.036, 95% CI 0.43-0.97), and Hispanic ethnicity as compared to non-Hispanic black (OR 1.64, p=0.021, 95% CI: 1.08-2.49). These predictors remained statistically significant after additionally adjusting for gender, household income, and tobacco use. Conclusions: Hispanic caregivers had significantly higher odds of MetS as compared to non-Hispanic black caregivers. The overall prevalence of MetS is high, demonstrating an alarming trend among low-income adults enrolled in an urban community-based trial.N

Social determinants of lifestyle and cardiovascular health in a minority community study for promotion of health

American College of Cardiology 67th Annual Scientific Session 2018. Orlando, USA. March 10-12, 2018

The role of context in implementation research for non-communicable diseases: Answering the 'how-to' dilemma.

IntroductionUnderstanding context and how this can be systematically assessed and incorporated is crucial to successful implementation. We describe how context has been assessed (including exploration or evaluation) in Global Alliance for Chronic Diseases (GACD) implementation research projects focused on improving health in people with or at risk of chronic disease and how contextual lessons were incorporated into the intervention or the implementation process.MethodsUsing a web-based semi-structured questionnaire, we conducted a cross-sectional survey to collect quantitative and qualitative data across GACD projects (n = 20) focusing on hypertension, diabetes and lung diseases. The use of context-specific data from project planning to evaluation was analyzed using mixed methods and a multi-layered context framework across five levels; 1) individual and family, 2) community, 3) healthcare setting, 4) local or district level, and 5) state or national level.ResultsProject teams used both qualitative and mixed methods to assess multiple levels of context (avg. = 4). Methodological approaches to assess context were identified as formal and informal assessments, engagement of stakeholders, use of locally adapted resources and materials, and use of diverse data sources. Contextual lessons were incorporated directly into the intervention by informing or adapting the intervention, improving intervention participation or improving communication with participants/stakeholders. Provision of services, equipment or information, continuous engagement with stakeholders, feedback for personnel to address gaps, and promoting institutionalization were themes identified to describe how contextual lessons are incorporated into the implementation process.ConclusionsContext is regarded as critical and influenced the design and implementation of the GACD funded chronic disease interventions. There are different approaches to assess and incorporate context as demonstrated by this study and further research is required to systematically evaluate contextual approaches in terms of how they contribute to effectiveness or implementation outcomes