Demographic and psychological factors in type 2 diabetes risk and progression

Demographic and positive psychological factors are relevant to Type 2 Diabetes (T2D) risk and progression, but the biological underpinnings are unclear. This PhD consists of four studies aiming to better understand the role of demographic and positive psychological factors on T2D risk and progression, and the biological mechanisms involved. Study 1 used data from a nationally representative cohort to examine a) the relationship between different types of subjective well-being and T2D incidence in initially healthy participants and b) the amount of association explained by sociodemographic, behavioural, and clinical characteristics. Hedonic but not eudaimonic well-being predicted lower T2D rate over 12 years. Sociodemographic, behavioural, and clinical factors together accounted for 36% of the association. Studies 2 and 3 used data from a laboratory stress testing study. Study 2 tested sex differences in inflammatory stress responses in people with existing T2D. Results showed that women with T2D produced larger interleukin(IL)-6 stress responses compared with men. Study 3 examined the association between hedonic well-being and inflammatory stress responses in individuals with T2D. Hedonic well-being was associated with lower inflammatory markers pre- and post-stress. Inflammatory stress responses did not differ in people varying in hedonic well-being. Study 4 is a 7.5-year follow-up of this laboratory study. Study 4 looked at the possible mediating role of IL-6 stress (re)activity in associations linking sex or hedonic well-being with health outcomes in participants with T2D. Results showed that women with T2D experienced worse mental health-related quality of life at follow-up and greater IL-6 stress responses at baseline predicted diminished mental health-related quality of life. IL-6 stress responsivity did not mediate the link between sex and mental health at follow-up. These findings highlight the role of hedonic well-being in T2D development. The relationship between sex or hedonic well-being with T2D outcomes may be mediated via increased inflammatory (re)activity

Enjoyment of life predicts reduced type 2 diabetes incidence over 12 years of follow-up: findings from the English Longitudinal Study of Ageing

BACKGROUND: Subjective well-being appears to be associated with reduced risk of type 2 diabetes (T2D). However, it is unknown whether this association is similar across different types of well-being. We examined the relationship between hedonic and eudaimonic well-being and incident T2D, and explored the role of sociodemographic, behavioural and clinical factors in these associations. METHODS: We used data from 4134 diabetes-free participants from the English Longitudinal Study of Ageing (mean age =64.97). Enjoyment of life and purpose in life were assessed using items from the CASP-19 to reflect hedonic and eudaimonic well-being, respectively. Participants reported T2D diagnosis over 12 years. We used Cox proportional hazards regression analyses and also explored the percentage of association explained by different covariates. RESULTS: Results revealed a protective role for enjoyment of life in T2D rate adjusting for sociodemographic (age, sex, wealth, ethnicity, marital status), behavioural (physical activity, smoking, alcohol consumption, body mass index) and clinical (hypertension, coronary heart disease and glycated haemoglobin) characteristics (HR =0.93, p=0.021, 95% CI (0.87, 0.99)). Sociodemographic, behavioural and clinical factors accounted for 27%, 27% and 18% of the association, respectively. The relationship between purpose in life and T2D was non-significant (adjusted HR =0.92, p=0.288, 95% CI (0.78, 1.08)). CONCLUSION: This study illustrates how the link between subjective well-being and T2D varies between well-being components. It also demonstrates that sociodemographic, behavioural and clinical factors partially explain this association. Intervention studies examining whether changes in enjoyment of life can help delay T2D onset are warranted

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships

Ca II H and K Chromospheric Emission Lines in Late K and M Dwarfs

We have measured the profiles of the Ca II H and K chromospheric emission lines in 147 main sequence stars of spectral type M5-K7 (0.30-0.55 solar masses) using multiple high resolution spectra obtained during six years with the HIRES spectrometer on the Keck 1 telescope. Remarkably, the average FWHM, equivalent widths, and line luminosities of Ca II H and K increase by a factor of 3 with increasing stellar mass over this small range of stellar masses. We fit the H and K lines with a double Gaussian model to represent both the chromospheric emission and the non-LTE central absorption. Most of the sample stars display a central absorption that is typically redshifted by ~0.1 km/s relative to the emission, but the nature of this velocity gradient remains unknown. The FWHM of the H and K lines increase with stellar luminosity, reminiscent of the Wilson-Bappu effect in FGK-type stars. Both the equivalent widths and FWHM exhibit modest temporal variability in individual stars. At a given value of M_v, stars exhibit a spread in both the equivalent width and FWHM of Ca II H and K, due both to a spread in fundamental stellar parameters including rotation rate, age, and possibly metallicity, and to the spread in stellar mass at a given M_v. The K line is consistently wider than the H line, as expected, and its central absorption is more redshifted, indicating that the H and K lines form at slightly different heights in the chromosphere where the velocities are slightly different. The equivalent width of H-alpha correlates with Ca II H and K only for stars having Ca II equivalent widths above ~2 angstroms, suggesting the existence of a magnetic threshold above which the lower and upper chromospheres become thermally coupled.Comment: 40 pages including 12 figures and 17 pages of tables, accepted for publication in PAS

Dysregulated responses to stress and weight in people with type 2 diabetes

OBJECTIVE: Dysregulated stress responsivity has been linked with weight gain in healthy samples. However, the relationship between disturbances in stress-related biology and changes in weight in people with type 2 diabetes (T2D) is unclear. METHOD: A total of 66 participants with T2D underwent laboratory stress-testing in 2011-2012. Cardiovascular, neuroendocrine and inflammatory responses to standardised mental stress were assessed, and Body Mass Index (BMI) was measured. Participants self-reported information on BMI in 2019. Associations between stress-related biological responses and BMI at follow-up were modelled using linear regression adjusting for age, sex, resting biological levels and baseline BMI. RESULTS: Blunted diastolic blood pressure reactivity (B = -0.092, 95% CI -0.177; -0.007, p = 0.034) as well as poorer systolic blood pressure (B = -0.050, 95% CI -0.084; - 0.017, p = 0.004), diastolic blood pressure (B = -0.068, 95% CI -0.132; -0.004, p = 0.034) and heart rate (B = -0.122, 95% CI -0.015;-0.230, p = 0.027) recovery post-stress were associated with higher BMI 7.5 years later. Greater interleukin-1 receptor antagonist (B = 16.93, 95% CI 6.20; 27.67, p = 0.003) and monocyte chemoattractant protein-1 reactivity (B = 0.04, 95% CI 0.002; 0.084, p = 0.041) were associated with weight gain. No significant associations were detected for interleukin-6 or laboratory cortisol measures. CONCLUSION: Disturbances in stress-related biology may promote weight gain in people with T2D. Research with a larger sample size is required to explore associations between stress responsivity and BMI in people with T2D