Frailty in midlife as a predictor of changes in body composition from midlife into old age: a longitudinal birth cohort study.

INTRODUCTION: Few studies have investigated the association between frailty and subsequent body composition. METHODS: We performed separate linear mixed model analyses to study the associations between changes in the participants frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI-ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. RESULTS: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI -ratio increased. Participants with 'stable frailty', followed by those with 'increasing frailty' experienced faster decreases in LMI and faster increases in FMI and FMI to LMI -ratio values from midlife into old age relative to those in the group 'stable not frail'. Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI -ratio became more frail faster from midlife into old age relative to those in the lowest third. CONCLUSIONS: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat to lean -ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.

The brain insulin receptor gene network and associations with frailty index.

OBJECTIVE: To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up. METHODS: This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001-2004, 2011-2013 and 2017-2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age. RESULTS: The FI levels of women were 1.19%-points (95% CI 0.12-2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increase in mean FI levels per year in either sex (P > 0.43). CONCLUSIONS: Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study.

BACKGROUND: Few studies have examined longitudinal changes in lifestyle-related factors and frailty. METHODS: We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57-69 years at baseline. RESULTS: A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted ß × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted ß × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted ß × Time = -0.10, 95%CI = -0.23, -0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted ß × Time = 0.16, 95% CI = 0.01, 0.30). CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.

Social Mobility and Health-Related Quality of Life Trajectory Classes Among Older Women and Men.

OBJECTIVES: Changes in socioeconomic status (SES) during life may impact health in old age. We investigated whether social mobility and childhood and adulthood SES are associated with trajectories of health-related quality of life (HrQoL) over a 17-year period. METHODS: We used data from the Helsinki Birth Cohort Study (n = 2003, 46% men, mean age 61.5 years). Social mobility was derived from childhood SES, obtained from healthcare records, and register-based adulthood SES. RESULTS: Logistic regression models showed that lower adulthood SES was associated with lower physical HrQoL trajectories. Among men low (OR 3.95, p < .001), middle (OR 2.20, p = .006), and declining lifetime SES (OR 2.41, p = .001) were associated with lower physical HrQoL trajectories compared to men with high SES. Socioeconomic status was not associated with mental HrQoL trajectories. DISCUSSION: Declining SES during life course may have negative health consequences, while improving SES is potentially as beneficial as high SES to later-life health among men.

Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women.

Background: To investigate associations between variations in the co-expression-based brain insulin receptor polygenic score and cardiometabolic risk factors and diabetes mellitus. Methods: This cross-sectional study included 1,573 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Cardiometabolic markers included body composition, waist circumference, circulating lipids, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 1 and 3 (IGFBP-1 and -3). Glucose and insulin levels were measured during a standardized 2-hour 75 g oral glucose tolerance test and impaired glucose regulation status was defined by the World Health Organization 2019 criteria. Analyzes were adjusted for population stratification, age, smoking, alcohol consumption, socioeconomic status, chronic diseases, birth weight, and leisure-time physical activity. Results: Multinomial logistic regression indicated that one standard deviation increase in hePRS-IR was associated with increased risk of diabetes mellitus in all participants (adjusted relative risk ratio, 1.17; 95% confidence interval, 1.01 to 1.35). In women, higher hePRS-IR was associated with greater waist circumference and higher body fat percentage, levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, insulin, and IGFBP-1 (all P≤0.02). The mePRS-IR was associated with decreased IGF-1 level in women (P=0.02). No associations were detected in men and studied outcomes. Conclusion: hePRS-IR is associated with sex-specific differences in cardiometabolic risk factor profiles including impaired glucose regulation, abnormal metabolic markers, and unfavorable body composition in women.

Healthy ageing from birth to age 84 years in the Helsinki Birth Cohort Study, Finland: a longitudinal study.

BACKGROUND: The true prevalence of healthy ageing on a population level is unknown. In this study we aimed to examine the upper limit for the prevalence of healthy ageing, by quantifying the probability of surviving and remaining free of chronic diseases that could impact functioning (ie, healthy survival) across adulthood. We also estimated the prevalence of clinically assessed healthy ageing, and the determinants of healthy survival and healthy ageing. METHODS: In this longitudinal study, we assessed men and women born in 1934-44 from the Helsinki Birth Cohort Study (Helsinki, Finland; n=13 140). We obtained information on chronic diseases, deaths, and early-to-midlife variables from national registers, databases, and health records for the period Jan 1, 1971, to Dec 31, 2017 (follow-up 951 088 person-years). We also collated data from clinical visits conducted in 2001-04 and 2017-18. Healthy ageing was defined on the basis of clinical data according to six criteria covering chronic diseases, cognitive function, physical performance, depressive symptoms, pain interference, and social functioning. We analysed the probability of healthy survival across adulthood using the Kaplan-Meier method, and the determinants of healthy survival using Cox regression models. We assessed the association of healthy ageing status in 2017-18 (n=813 with available data) with late-midlife factors collected in 2001-04 using age-adjusted logistic regression. FINDINGS: The probability of healthy survival was 42·8% (95% CI 41·6-44·0) in men and 40·1% (38·9-41·4) in women at age 65 years, and 22·5% (21·5-23·6%) in men and 24·4% (23·3-25·6) in women at age 75 years. Healthy survival was associated with socioeconomic position in childhood (adjusted hazard ratio [aHR], upper-middle class vs manual worker, men: 1·21 [1·11-1·31]; women: 1·15 [95% CI 1·05-1·26]) and years of education (aHR per 1 SD increase, men: 1·12 [1·08-1·16]; women: 1·03 [1·00-1·07]). In men, healthy survival was also associated with lower maternal BMI in late pregnancy (aHR per 1 SD increase 0·93 [0·90-0·96]), and in women, with shorter height at age 7 years (aHR per 1 SD increase 0·95 [0·91-0·99]). Among the 813 individuals with relevant clinical assessment data, 159 (19·6%) met all six criteria for healthy ageing at mean age 76 years (SD 3). In addition to age, we found that nutrition (Alternative Healthy Eating Index, age-adjusted odds ratio [aOR] per 1 point increase 1·03 [1·01-1·05]), former smoker status (vs non-smoker status, aOR 0·68 [0·47-0·98], and use of lipid-lowering medication (vs not used, aOR 0·60 [0·42-0·87]) in late midlife (mean age 61 years [SD 3]) were associated with healthy ageing. INTERPRETATION: The probability of healthy survival, as the upper limit for healthy ageing, was less than 50% from age 65 years. The probability of healthy survival and healthy ageing was influenced by several factors across the life course. Promotion of healthy ageing needs to take a life course approach. FUNDING: Signe and Ane Gyllenberg Foundation, Samfundet Folkhälsan, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, European Commission Seventh Framework Programme, EU Horizon 2020, and the Academy of Finland.

Circulating Cytokine Levels and Cardiovascular Disease Risk Profile in Young Adult Offspring of Women with Type 1 Diabetes.

INTRODUCTION: Cytokines are key players in the development of both type 1 diabetes (T1D) and cardiovascular disease (CVD). Offspring of women with T1D are known to have an increased risk of early-onset CVD. We studied whether an increased risk of CVD can be observed in the cytokine profile among young adult offspring of women with T1D. METHODS: This cross-sectional case-control study included 67 offspring of women with T1D (cases) and 79 control participants (controls). At an age of 18-23 years, they participated in a clinical assessment including laboratory tests and questionnaires. Cytokine levels were analyzed from venous blood samples after 10 h fasting using Quansys biosciences Q-Plex™ High Sensitivity Human Cytokine Array. RESULTS: Circulating cytokine levels were in general similar between the groups. The circulating levels of interferon-γ (1.78 [IQR 1.20, 2.36] pg/mL versus 2.57 [IQR 1.50, 3.89] pg/mL) (p = 0.006) were lower in cases than controls. CONCLUSION: The findings did not support our hypothesis that serum cytokine profile, determined in early adulthood, was associated with a more adverse CVD risk profile in offspring of women with T1D. Further studies are warranted to find out whether cytokines could serve as early biomarkers of CVD development or whether changes in the cytokine levels over years could be used to monitor CVD progression in offspring of women with T1D.

Body Composition in Late Midlife as a Predictor of Accelerated Age-associated Deficit-accumulation From Late Midlife into Old Age: A Longitudinal Birth Cohort Study.

BACKGROUND: Body mass index (BMI) may not be an optimal predictor of frailty as its constituents, lean and fat mass, may have opposite associations with frailty. METHODS: A linear mixed model analysis was performed in the Helsinki Birth Cohort Study (n = 2 000) spanning from 57 to 84 years. A 39-item frailty index (FI) was calculated on three occasions over 17 years. Body composition in late midlife included BMI, percent body fat (%BF), waist-to-hip ratio (WHR), lean mass index (LMI), and fat mass index (FMI). RESULTS: Mean FI levels increased by 0.28%/year among men and by 0.34%/year among women. Among women, per each kg/m2 higher BMI and each unit higher %BF the increases in FI levels per year were 0.013 percentage points (PP) steeper (95% CI = 0.004, 0.023) and 0.009 PP steeper (95% CI = 0.002, 0.016) from late midlife into old age. Among men, per each 0.1-unit greater WHR the increase in FI levels was 0.074 PP steeper per year (95% CI = -0.0004, 0.148). Cross-sectionally, greater FMI and LMI in late midlife were associated with higher FI levels but the direction of the association regarding LMI changed after adjustment for FMI. The categories "high FMI and high LMI" and "high FMI and low LMI" showed the highest FI levels relative to the category "low FMI and low LMI". CONCLUSIONS: In late midlife, greater adiposity (%BF) among women and abdominal obesity (WHR) among men may predispose to higher levels of frailty from late midlife into old age. Greater lean mass alone may be protective of frailty, but not in the presence of high fat mass.

Depressive symptoms and mortality-findings from Helsinki birth cohort study.

BACKGROUND: Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon. METHODS: One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated. RESULTS: Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02-2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85-1.44)] and melancholic depressive [1.26 (95% CI: 0.87-1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73-0.93)]. CONCLUSIONS: Melancholic depressive symptoms are most strongly related to a higher mortality risk.

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case-control study.

BACKGROUND: Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. METHODS: This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. RESULTS: We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, HbA1c, and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. CONCLUSIONS: We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.

Adiposity-Related Predictors of Vascular Aging From a Life Course Perspective-Findings From the Helsinki Birth Cohort Study.

The main objective of this study was to study predictors of vascular health with focus on adiposity-related factors. Glucose metabolism, blood lipids, inflammatory markers and body composition were assessed 15 years before assessment of vascular health which was assessed with pulse wave velocity (PWV) in 660 subjects born 1934-44. In a univariate analysis in women the strongest association with PWV was seen for age, systolic blood pressure, dysglycemia, dyslipidemia, inflammatory markers and body fat percentage measured in late midlife and PWV measured 15 years later. In men age, body mass index (BMI), systolic blood pressure, dysglycemia, and body fat percentage in late midlife were associated with PWV. One novel finding was that adiposity-related factors were strong predictors of vascular health, something not fully encapsulated in BMI, lean body mass or body fat percentage alone. A higher fat mass index was associated with worse vascular health, which was not ameliorated by a higher lean mass index. Our findings stress the importance to study body composition and fat and lean body mass simultaneously because of their close interaction with each other also in relation to vascular health.

Non-melancholic depressive symptoms are associated with above average fat mass index in the Helsinki birth cohort study.

There is an existing link between two of the most common diseases, obesity and depression. These are both of great public health concern, but little is known about the relationships between the subtypes of these conditions. We hypothesized that non-melancholic depressive symptoms have a stronger relationship with both body composition (lean mass and fat mass) and dysfunctional glucose metabolism than melancholic depression. For this cross-sectional study 1510 participants from the Helsinki Birth Cohort Study had their body composition evaluated as lean mass and fat mass (Lean Mass Index [LMI, kg/m2] + Fat Mass Index [FMI kg/m2] = Body Mass Index). Participants were evaluated for depressive symptoms utilizing the Beck depression inventory, and had laboratory assessments including an oral glucose tolerance test. Higher than average FMI was associated with a higher percentage (mean [%], 95% CI) of participants scoring in the depressive range of the Beck depression inventory (20.2, 17.2-23.2) compared to those with low FMI (16.3, 13.8-18.9; p = 0.048) when adjusted for age, sex, education, and fasting plasma glucose concentration. Higher FMI was associated with a higher likelihood of having depressive symptoms (OR per 1-SD FMI = 1.37, 95% CI 1.13-1.65), whereas higher LMI was associated with a lower likelihood of having depressive symptoms (OR per 1-SD LMI = 0.76, 95% CI 0.64-0.91). Participants with an above average FMI more frequently (mean [%], 95% CI) had non-melancholic depressive symptoms (14.7, 11.8-17.7) as compared to those with low FMI (9.7, 7.6-11.9; p = 0.008) regardless of LMI levels. There was no difference between the body composition groups in the likelihood of having melancholic depressive symptoms. The non-melancholic group had higher (mean [kg/m2], SD) FMI (9.6, 4.1) than either of the other groups (BDI < 10: 7.7, 3.1; melancholic: 7.9, 3.6; p < 0.001), and a higher (mean [mmol/l], SD) 2-h glucose concentration (7.21, 1.65) than the non-depressed group (6.71, 1.70; p = 0.005). As hypothesized, non-melancholic depressive symptoms are most closely related to high fat mass index and dysfunctional glucose metabolism.

Effect of childhood developmental coordination disorder on adulthood physical activity; Arvo Ylppö longitudinal study.

Individuals at risk of Developmental Coordination Disorder (DCD) have low levels of physical activity in childhood due to impaired motor competence; however, physical activity levels in adulthood have not been established. This study sought to determine the impact of DCD risk on physical activity levels in adults using accelerometry measurement. Participants (n = 656) from the Arvo Ylppö Longitudinal Study cohort had their motor competence assessed at the age of five years, and their physical activity quantified via device assessment at the age of 25 years. Between group differences were assessed to differentiate physical activity measures for individuals based on DCD risk status, with general linear modeling performed to control for the effects of sex, body mass index (BMI), and maternal education. Participants at risk of DCD were found to have a lower total number of steps (d = 0.3, p = 0.022) than those not at risk. Statistical modeling indicated that DCD risk status increased time spent in sedentary light activity (ß = 0.1, 95% CI 0.02 to 0.3, p = 0.026) and decreased time spent in vigorous physical activity via interaction with BMI (ß = 0.04, 95% CI 0.001 to 0.1, p = 0.025). Sensitivity analysis found that visuomotor impairment did not significantly impact physical activity but did increase the role of DCD risk status in some models. This 20-year-longitudinal study indicated that DCD risk status continues to negatively impact on levels of physical activity into early adulthood.

Early-Life Factors as Predictors of Age-Associated Deficit Accumulation Across 17 Years From Midlife Into Old Age.

BACKGROUND: Early-life exposures have been associated with the risk of frailty in old age. We investigated whether early-life exposures predict the level and rate of change in a frailty index (FI) from midlife into old age. METHODS: A linear mixed model analysis was performed using data from 3 measurement occasions over 17 years in participants from the Helsinki Birth Cohort Study (n = 2 000) aged 57-84 years. A 41-item FI was calculated on each occasion. Information on birth size, maternal body mass index (BMI), growth in infancy and childhood, childhood socioeconomic status (SES), and early-life stress (wartime separation from both parents) was obtained from registers and health care records. RESULTS: At age 57 years the mean FI level was 0.186 and the FI levels increased by 0.34%/year from midlife into old age. Larger body size at birth associated with a slower increase in FI levels from midlife into old age. Per 1 kg greater birth weight the increase in FI levels per year was -0.087 percentage points slower (95% confidence interval = -0.163, -0.011; p = 0.026). Higher maternal BMI was associated with a higher offspring FI level in midlife and a slower increase in FI levels into old age. Larger size, faster growth from infancy to childhood, and low SES in childhood were all associated with a lower FI level in midlife but not with its rate of change. CONCLUSIONS: Early-life factors seem to contribute to disparities in frailty from midlife into old age. Early-life factors may identify groups that could benefit from frailty prevention, optimally initiated early in life.

Evaluation of Afterschool Activity Programs' (ASAP) Effect on Children's Physical Activity, Physical Health, and Fundamental Movement Skills.

BACKGROUND: Physical literacy-focused afterschool activity programs (ASAPs) can be an effective strategy to improve children's health-related parameters. We sought to compare physical activity, body composition, aerobic capacity, and fundamental movement skills between physical literacy-focused ASAP and a standard recreational ASAP. METHOD: A pre-post (6 months) comparison study was conducted in 5- to 12-year-old children in a physical literacy-focused ASAP (physical literacy group, n = 14) and children attending a standard recreational ASAP (comparison group, n = 15). Physical activity guideline adherence was assessed using accelerometry, body composition was analyzed using bioelectrical impedance, aerobic capacity was estimated using the Progressive Aerobic Cardiovascular Endurance Run test, and fundamental movement skills were evaluated using the Test of Gross Motor Development-2. RESULTS: There were no significant differences between groups at baseline. After 6 months, the physical literacy group exhibited a significant improvement in their total raw score for the Test of Gross Motor Development-2 (p = .016), which was likely due to improvements in object control skills (p = .024). The comparison group significantly increased body mass index (p = .001) and body fat (p = .009) over time. No significant between-group differences were found; however, there was a trend for improved aerobic capacity in the physical literacy group (d = 0.58). CONCLUSIONS: Engagement in the physical literacy-focused ASAP contributed to an attenuated increase in adiposity and an improvement in object control skills.

Mental, Physical and Social Functioning in Independently Living Senior House Residents and Community-Dwelling Older Adults.

Senior houses provide social interaction and support, potentially supporting older people's physical and mental functioning. Few studies have investigated functioning of senior house residents. The aim was to compare functioning between senior house residents and community-dwelling older adults in Finland. We compared senior house residents (n = 336, 69% women, mean age 83 years) to community-dwelling older adults (n = 1139, 56% women, mean age 74 years). Physical and mental functioning were assessed using the SF 36-Item Health Survey. Loneliness and frequency of social contacts were self-reported. The analyses were adjusted for age, socioeconomic factors and diseases. Physical functioning was lower among men in senior houses compared to community-dwelling men (mean 41.1 vs. 46.4, p = 0.003). Mental functioning or the frequency of social contacts did not differ between type of residence in either sex. Loneliness was higher among women in senior houses compared to community-dwelling women (OR = 1.67, p = 0.027). This was not observed in men. Results suggest that women in senior houses had similar physical and mental functioning compared to community-dwelling women. Male senior house residents had poorer physical functioning compared to community-dwelling men. Women living in senior houses were lonelier than community-dwelling women despite the social environment.

Late-Pregnancy Fetal Hypoxia Is Associated With Altered Glucose Metabolism and Adiposity in Young Adult Offspring of Women With Type 1 Diabetes.

Objective: To investigate associations between exposure to fetal hypoxia and indicators of metabolic health in young adult offspring of women with type 1 diabetes (OT1D). Methods: 156 OT1D born between 7/1995 and 12/2000 at Helsinki University Hospital, Finland, were invited for follow-up between 3/2019 and 11/2019. A control group of 442 adults born from non-diabetic pregnancies, matched for date and place of birth, was obtained from the Finnish Medical Birth Register. In total, 58 OT1D and 86 controls agreed to participate. All OT1D had amniotic fluid (AF) sampled for erythropoietin (EPO) measurement within two days before delivery in order to diagnose fetal hypoxia. In total, 29 OTID had an AF EPO concentration <14.0 mU/l, defined as normal, and were categorized into the low EPO (L-EPO) group. The remaining 29 OT1D had AF EPO ≥14.0 mU/ml, defined as fetal hypoxia, and were categorized into the high EPO (H-EPO) group. At the age of 18-23 years, participants underwent a 2-h 75g oral glucose tolerance test (OGTT) in addition to height, weight, waist circumference, body composition, blood pressure, HbA1c, cholesterol, triglyceride, high-sensitivity CRP and leisure-time physical activity measurements. Results: Two OT1D were diagnosed with diabetes and excluded from further analyses. At young adult age, OT1D in the H-EPO group had a higher BMI than those in the L-EPO group. In addition, among female participants, waist circumference and body fat percentage were highest in the H-EPO group. In the OGTTs, the mean (SD) 2-h post-load plasma glucose (mmol/L) was higher in the H-EPO [6.50 (2.11)] than in the L-EPO [5.21 (1.10)] or control [5.67 (1.48)] offspring (p=0.009). AF EPO concentrations correlated positively with 2-h post-load plasma glucose [r=0.35 (95% CI: 0.07 to 0.62)] and serum insulin [r=0.44 (95% CI: 0.14 to 0.69)] concentrations, even after adjusting for maternal BMI, birth weight z-score, gestational age at birth and adult BMI. Control, L-EPO and H-EPO groups did not differ with regards to other assessed parameters. Conclusions: High AF EPO concentrations in late pregnancy, indicating fetal hypoxia, are associated with increased adiposity and elevated post-load glucose and insulin concentrations in young adult OT1D.

The relationship between health-related quality of life and melancholic depressive symptoms is modified by brain insulin receptor gene network.

To investigate whether expression-based polygenic risk scores for the insulin receptor gene network (ePRS-IRs) modifiy the association between type of depressive symptoms and health-related quality of life (HRQoL). This cross-sectional study includes 1558 individuals from the Helsinki Birth Cohort Study. Between 2001 and 2004, the Short Form-36 questionnaire was employed to assess mental and physical components of HRQoL and Beck Depression Inventory (BDI) to assess depressive symptoms. Depressive symptoms were categorized into minimal (BDI < 10), non-melancholic and melancholic types of depression. The ePRS-IRs were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions of the brain. General linear regression models adjusted for age, sex, population stratification, lifestyle factors and body mass index were applied to analyze the data. Both types of depressive symptoms were associated with lower HRQoL (p < 0.0001). HePRS-IR modified the association between the types of depression and mental HRQoL (p for interaction = 0.005). Melancholic type of depressive symptoms was associated with higher mental HRQoL compared to the non-melancholic symptoms among individuals with low hePRS-IR (adjusted mean 4.1, 95% CI 0.7-7.4, p = 0.018). However, no such difference was evident in moderate or high hePRS-IR groups as higher hePRS-IR was associated with lower mental HRQoL (B = - 3.4, 95% CI - 5.6 to - 1.2) in individuals with melancholic type of depressive symptoms. No direct associations were detected between the ePRS-IRs and type of depressive symptoms or HRQoL. Variations in the glucose-insulin metabolism can lower HRQoL in individuals with melancholic depressive symptoms.

Advanced glycation end products measured by skin autofluorescence are associated with melancholic depressive symptoms - Findings from Helsinki Birth Cohort Study.

BACKGROUND: Millions of people live with depression and its burden of disease. Depression has an increased comorbidity and mortality that has remained unexplained. Studies have reported connections between advanced glycation end products (AGEs) and various disease processes, including mental health. The present study evaluated associations between AGEs, depressive symptoms, and types of depressive symptoms. METHODS: From the Helsinki Birth Cohort Study, 815 participants with a mean age of 76 years were recruited for this cross-sectional study. Characteristics regarding self-reported lifestyle and medical history, as well as blood tests were obtained along with responses regarding depressive symptoms according to the Beck Depression Inventory (BDI) and Mental Health Inventory-5. Each participant had their AGE level measured non-invasively with skin autofluorescence (SAF). Statistical analyses looked at relationships between types of depressive symptoms and AGE levels by sex. RESULTS: Of women, 27% scored ≥10 on the BDI and 18% of men, respectively. Men had higher crude AGE levels (mean [standard deviation], arbitrary units) (2.49 [0.51]) compared to women (2.33 [0.46]) (p < 0.001). The highest crude AGE levels were found in those with melancholic depressive symptoms (2.61 [0.57]), followed by those with non-melancholic depressive symptoms (2.45 [0.45]) and those with no depressive symptoms (2.38 [0.49]) (p = 0.013). These findings remained significant in the fully adjusted model. CONCLUSIONS: The current study shows an association between depressive symptoms and higher AGE levels. The association is likely part of a multi-factorial effect, and hence no directionality, causality, or effect can be inferred solely based on the results of this study.

Higher carotid-radial pulse wave velocity is associated with non-melancholic depressive symptoms in men - findings from Helsinki Birth Cohort Study.

BACKGROUND: Depression and cardiovascular disease (CVD) are major causes of global disease burden that are interrelated through mostly unknown mechanisms. We studied the relationship of melancholic and non-melancholic depressive symptoms with arterial stiffness, an important underlying mechanism of CVD. METHODS: The Helsinki Birth Cohort Study recruited 683 previously extensively phenotyped subjects for this sub-study. Cross-sectional data along with responses regarding depressive symptoms were obtained for each participant. For evaluation of depressive symptoms, the Beck Depression Inventory (BDI)and subscales were used to measure melancholic and non-melancholic depressive symptoms. Arterial stiffness was assessed as pulse wave velocity (PWV) that was measured between the carotid and radial artery, and carotid and femoral artery. RESULTS: Of the participants, 532 scored <10 on the BDI and were classified as not having depressive symptoms. Of the 151 participants that scored ≥10 on the BDI, 122 were classified as having non-melancholic depressive symptoms and 29 as having melancholic depressive symptoms. Men had higher carotid-radial PWV (crPWV) values than women (p < .001). A positive relationship between BDI scores and crPWV (p < .001) was found in men. We also found higher crPWV in men with non-melancholic depressive symptoms compared to all others. No such differences were found in women. DISCUSSION: Arterial stiffness has a relationship with depressive symptoms and subtypes of depressive symptoms, at least in men. There is a significant relationship between higher PWV and non-melancholic depressive symptoms in men. Due to the intricate nature of the disease causality or directionality is impossible to infer solely based on this study. Further studies into the subtypes of depressive symptoms may be of benefit to understanding depression.KEY MESSAGESIt is known that arterial stiffness contributes to cardiovascular disease, and is associated with depression.Higher Beck Depression Inventory scores are associated with higher carotid-radial pulse wave velocity in men.Non-melancholic depressive symptoms are associated with higher carotid-radial pulse wave velocity in men.