The Effect of Diabetes and the Diabetogenic TBC1D4 p.Arg684Ter Variant on Kidney Function in Inuit in Greenland

ObjectiveDiabetes prevalence in Greenland is high and increasing. The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting.Research Design and MethodsHealth survey data and TBC1D4 genotypes from 5,336 Greenlanders was used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR<60 ml/min/1.73m2), comparing individuals with and without diabetes. Using baseline and follow-up data from individuals who participated in two surveys we examined the effect of diabetes on eGFR and urinary albumin creatinine ratio (UACR) at follow-up, stepwise adjusting for baseline confounders including the TBC1D4 variant.ResultsA total of 9.3% had diabetes of the 3,909 participants with complete data. Albuminuria and CKD was found in 27.6% and 9.5% among those with and without diabetes respectively. Diabetes was associated with increased risk of albuminuria (OR(95% CI) = 2.37 (1.69,3.33) p<0.001) and the TBC1D4 variant protected against albuminuria (OR(95% CI) = 0.44 (0.22,0.90) p=0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. Diabetes was not associated with changes in eGFR or UACR over a median of 11.3 years.ConclusionDiabetes conferred increased risk of albuminuria and the TBC1D4 variant was associated with decreased risk of albuminuria, but neither were associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.

Longitudinal Analyses Indicate Bidirectional Associations Between Loneliness and Self-Rated Health in Adulthood

Loneliness is a potent stressor that increases in prevalence with age in late life and has been linked with numerous adverse physical health outcomes and lower scores on measures of self-rated health (SRH). The association between loneliness and SRH is likely bidirectional—for example, experiencing loneliness may result in physiological changes that alter how individuals perceive their health, and worsening perceptions of one’s own health or mobility may act in an increasingly restrictive manner with respect to social interaction. Despite this, limited longitudinal work has examined temporal dynamics between loneliness and SRH. Recently completed harmonization of 9 loneliness items across three longitudinal twin studies of aging in Sweden resulted in sample of 1939 participants aged 40 to 98 at intake (mean age = 74.64) with up to 25 years of follow-up (mean = 7.63) across up to 8 waves (mean = 3.29). Univariate analysis indicated that SRH decreased with age up to age 82 and then leveled off, whereas loneliness continued to increase across the age span. Bivariate dual change score models were used to examine lead-lag relationships across time: which variable contributes to subsequent changes in the other variable. Results indicated a bi-directional relationship: loneliness does not increase after age 82 when SRH is included in the model, and SRH does not level off after age 70 when loneliness is included in the model. Thus, declining SRH may lead to reduced participation in social activities and also feelings of loneliness may intensify perceptions of poor health.

The Longitudinal Relationship Between Engagement in Various Activities and Cognitive Functioning

Recent studies indicate that engaging in more diverse activities is related to higher cognitive functioning. Questions remain, however, regarding whether activity variety within different domains is important. We examined how overall activity variety across domains, as well as variety within cognitive, physical, and social domains are related to cognitive functioning. Data were drawn from Waves 2-3 of Midlife Development in the United States (MIDUS). In cross-sectional analyses (N = 3349), activity variety overall and within each domain were positively related to cognitive functioning regardless of activity frequency. In longitudinal analyses (n = 2054), participants with consistently higher activity variety overall and within the social domain over time (vs. those with consistently low or decreasing activity variety) exhibited better cognitive functioning at W3 after adjusting for cognitive functioning at W2. Findings suggest that engaging in a variety of activities that involve multiple cognitive processes might be beneficial for cognitive health.

Impact of Hypothyroidism on Tomography and Biomechanics in Keratoconus – Cross-Sectional and Longitudinal Assessment within the Homburg Keratoconus Center at the Time of Inclusion and after 1 Year

Background and Purpose The etiology of keratoconus (KC) is probably multifactorial but remains essentially unknown. Previous scientific observations have suggested that hypothyroidism might play a role in the development and progression of KC. The purpose of this study was to analyze the tomographic and biomechanical parameters in KC patients with or without hypothyroidism. Methods Twenty-eight patients with KC and hypothyroidism (HT group) and fifty-six KC patients without thyroid dysfunction (WHT group) with matching gender and age were analyzed. Mean age was 40.3 years (range 14 – 57) in the HT group and 40.3 years (range 14 – 57) in the WHT group. Routine ophthalmic examinations consisted of corneal tomography and biomechanical parameters. We extracted the following KC parameters from the Pentacam (Pentacam HR, Oculus, Wetzlar, Germany): Keratoconus Index (KI), maximum keratometry (Kmax), astigmatism, and thinnest pachymetry (TP). From the ocular response analyzer (ORA, Reichert Ophthalmic Instruments, Depew, NY, USA), we extracted corneal hysteresis (CH), corneal resistance factor (CRF), and KC match index (KMI). Results The comparison of the tomographic and biomechanical values from cross-sectional and longitudinal analyses showed no significant differences between the HT and WHT groups. Conclusion The severity of KC based on tomographical and biomechanical parameters does not seem to depend on the presence of hypothyroidism.

Factors Associated With Hypertension Awareness, Treatment, and Control Among Adults in Kerala, India

Background: Hypertension, the most significant risk factor for cardiovascular disease, is an increasing contributor to global health burden, particularly in low- and middle-income countries (LMICs) such as India. While the rates of hypertension awareness, treatment, and control in India have been reported in several studies, the factors associated with these rates are less well-understood. Existing studies are predominantly cross-sectional, and the factors examined are limited. Understanding the predictors associated with these rates, using more rigorous study designs, is crucial for the development of strategies to improve hypertension management.Aims: To examine a range of factors associated with hypertension awareness, treatment, and control using both cross-sectional and longitudinal analyses.Methods: Data was derived from a population-based sample of 1,710 participants from Kerala, aged 30–60 years. We examined a comprehensive range of factors, including demographic, behavioral factors, anthropometric, clinical measures, psychosocial factors and healthcare utilization. Multilevel mixed effects logistic regression was used for both cross-sectional and longitudinal analyses (repeated measures for all variables across 2 years) to determine the factors associated with awareness, treatment, and control of hypertension.Results: A total of 467 (27.3%) participants had hypertension at baseline. Among those, the rates of awareness, treatment, and control of hypertension were 54.4, 25.5, and 36.4%, respectively. Being male (OR 0.27, 95% CI 0.14–0.53) and consumption of alcohol (OR 0.49, 95% CI 0.31–0.80) were significant predictors of poorly controlled hypertension (longitudinal analysis). Depression (OR 2.04, 95% CI 1.15–3.61) and fair-to-poor self-perceived health status (OR 1.87, 95% CI 1.15–3.04) were associated with increased hypertension awareness, whereas anxiety (OR 1.97, 95% CI 1.04–3.71) was associated with increased hypertension treatment (cross-sectional analysis). Seeking outpatient service in the past 4 weeks was associated with higher awareness (OR 1.09, 95% CI 1.27–2.87), treatment (OR 1.73, 95% CI 1.20–2.50) and control (OR 1.96, 95% CI 1.37–2.80) (longitudinal analysis).Conclusion: Our findings suggest the importance of considering psychosocial factors and better engagement with health services in hypertension management, as well as giving more attention to body fat control and largely male-related behaviors such as alcohol consumption, taking into account of some Indian specific attributes.

DNA methylation in peripheral tissues and Left-handedness

Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study (EWAS) of left-handedness. In a meta-analysis of 3,914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. We identified differentially methylated regions at 20q11.23 (P = 0.00004) and 2p25.1 (P = 0.03), which were less methylated in left-handed adults. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1,737), we observed moderately stable associations across age (correlation range [0.355–0.578]) but inconsistent across tissues (correlation range [-0.384-0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.