Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort.

BACKGROUND: The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. METHODS AND RESULTS: One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. CONCLUSIONS: This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.

Sex-related differences in the association of salivary cortisol levels and type 2 diabetes. Findings from the cross-sectional population based KORA-age study.

BACKGROUND: Dysregulation in the cortisol secretion may have a role in the development of type 2 diabetes although conflicting evidence on the particular cortisol secretion patterns and type 2 diabetes demands further investigations. We aim to examine the association of cortisol levels and diurnal secretion patterns with prevalence of type 2 diabetes and HbA1c levels as well as the potential impact of sex and adiposity on this association. METHODS: A cross-sectional analysis was conducted among 757 participants (aged 65-90 years) of the population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age study. Multivariate regression analyses were employed to examine the association between salivary cortisol (measured upon waking (M1), 30min after awakening (M2), and in the late night (LNSC)) and type 2 diabetes as well as glycated hemoglobin (HbA1c) with adjustments for potential confounders. RESULTS: In the total sample population, an elevated LNSC level was observed in type 2 diabetes patients compared to non-patients (P=0.04). In sex-stratified analyses, diabetic men showed a greater Cortisol Awakening Response (CAR) (P=0.02). Diabetic women had significantly elevated LNSC levels (P=0.04). HbA1c was positively associated with both CAR and LNSC levels but was negatively associated with M1 to LNSC ratio. CONCLUSION: In this aged population, type 2 diabetes is associated with dysregulated cortisol secretion characterized by distinct sex specific diurnal patterns.

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

STUDY OBJECTIVES: To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. METHODS: Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. RESULTS: At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (ß = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (ß = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. CONCLUSIONS: DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function.

Oxytocin-induced coping with stressful life events in old age depends on attachment: findings from the cross-sectional KORA Age study.

BACKGROUND: Whether oxytocin functions as a stress hormone in older age is unknown. We investigated oxytocin levels and the perceived stress of an adverse life event in an older population-representative sample and considered the effect of a secure/insecure attachment style on this association. METHODS: Non-fasting plasma oxytocin was measured from 952 participants (65-90 years) of the cross sectional KORA-Age study. The psychological impact of an adverse life event was assessed based on the Psychosocial Stress Questionnaire. Attachment style was determined by the Relationship-Specific Attachment Scales for Adults. Linear regression models of oxytocin, stratified for attachment style, were controlled for age, sex, and further for alcohol, smoking, and physical activity. Adjusted least squares means of oxytocin were calculated. RESULTS: Oxytocin levels did not differ between men and women (mean, 95% confidence interval (CI), 321 (277-365) and 309 (272-345)pg/ml, respectively). Oxytocin levels were positively associated with the experience of an adverse event (n=273, 29%) versus no event (n=679, 71%), in securely attached (ß estimate=0.17, standard error (SE)=0.08, P value=0.03) but not in insecure participants (-0.10, 0.09), P=0.28). Oxytocin was positively associated with diminished stress among securely attached participant (event with little suffering: ß=0.35. SE=0.12, great suffering: ß=0.15. SE=0.14, severe suffering: ß=0.03. SE=0.12). Among participants who reported minimal suffering, insecure individuals had lower oxytocin (adjusted mean, 95%CI: 172, 127-216 pg/ml) than securely attached individuals (279, 222-352 pg/ml, P=0.006). CONCLUSIONS: These epidemiologic data support the hypothesis that oxytocin may have an attenuating effect on perceived stress due to adverse life events in old age. The conditional role of attachment style in stress-induced endogenous oxytocin production is highlighted.

A pattern of unspecific somatic symptoms as long-term premonitory signs of type 2 diabetes: findings from the population-based MONICA/KORA cohort study, 1984-2009.

BACKGROUND: Unspecific symptoms often proceed a serious chronic disease condition long before the onset of the disease. The role of an unspecific premonitory symptom (UPMS) pattern as premonitory signs of subsequent type 2 diabetes mellitus (T2DM) diagnosis independent of established cardio-metabolic risk factors is unclear and therefore was examined in the present study. METHODS: The study population consisted of 10,566 participants aged 25-74 years at baseline drawn from the population-based MONICA/KORA Cohort Study conducted in 1984-2009 in the Augsburg region (Germany). Unspecific premonitory symptoms were assessed following the Somatic Symptom Scale-8 (SSS-8). The impact of the score on T2DM risk within a mean follow-up time of 16 years was estimated by Cox regression. RESULTS: Within follow-up, 974 newly diagnosed T2DM cases were observed. The risk for T2DM increased by a hazard ratio (HR) of 1.03 (95% CI 1.01-1.04, p value < 0.001) for a one unit increase of the UPMS score in a Cox model adjusted for age, sex and survey. Additional adjustment for cardio-metabolic risk factors attenuated this effect (HR = 1.02) but significance remained (p value = 0.01). CONCLUSIONS: Suffering from an elevated burden of unspecific somatic symptoms is associated with T2DM long before the onset and independent of established cardio-metabolic risk factors. Further research is needed to obtain insight in potential underlying pathophysiological mechanisms.

Prevalence of use and level of awareness of CAM in older people - results from the KORA-Age study.

BACKGROUND: Despite the growing proportion of older adults in Europe there is only limited knowledge of CAM use among the elderly. This analysis aims to provide estimates for the prevalence of CAM use in persons with an age of ≥65, and to investigate correlations of CAM use with demographic characteristics. METHODS: Based on participants of the MONICA/KORA studies S1-S4 who were born before 1944, a random sample of 1,079 was selected for comprehensive medical examinations. Questions were presented in structured face-to-face interviews conducted from February to November 2009. RESULTS: Data on CAM use were available for 1,026 subjects with a mean age of 76 years, ranging from 65 to 93 years. 14% of the participants were unaware of CAM. The overall prevalence of CAM use was estimated 37% with minor differences between age groups, but clear differences between male (29%) and female (44%) participants. 1-year prevalence of CAM use was 22% (16% males, 28% females). 1-year of CAM use was associated with a higher level of education in both men and women; with higher income in men; and with more actual diseases in women. CONCLUSION: Findings indicate that awareness of CAM is high even among people ≥65 years. Estimates for the prevalence of CAM use confirm the relevance of this treatment sector in the healthcare system for the elderly.

Job strain as a risk factor for the onset of type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

OBJECTIVE: To examine whether job strain is associated with an increased risk of subsequent Type 2 diabetes mellitus (T2DM) development in a population-based study of men and women. METHODS: Data were derived from the prospective MONICA/KORA Augsburg study. We investigated 5337 working participants aged 29 to 66 years without diabetes at one of the three baseline surveys. Job strain was measured by the Karasek job content questionnaire. High job strain was defined by the quadrant approach, where high job demands combined with low job control were classified as high job strain. Continuous job strain (quotient of job demands divided by job control) was additionally analyzed as sensitivity analysis. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with adjustment for age, sex, survey, socioeconomic and life-style variables, parental history of diabetes, and body mass index. RESULTS: During a median follow-up of 12.7 years, 291 incident cases of T2DM were observed. The participants with high job strain at baseline had a 45% higher fully adjusted risk to develop T2DM than did those with low job strain (HR = 1.45 [95% confidence interval = 1.00-2.10], p = .048). On the continuous scale, more severe job strain in the magnitude of 1 standard deviation corresponded to a 12% increased fully adjusted T2DM risk (HR = 1.12 [95% confidence interval = 1.00-1.25], p = .045). CONCLUSIONS: Men and women who experience high job strain are at higher risk for developing T2DM independently of traditional risk factors. Preventive strategies to combat the globally increasing T2DM epidemic should take into consideration the adverse effects of high strain in the work environment.

Aging without depression: a cross-sectional study.

OBJECTIVES: The aim of the study was to analyze the association between secure attachment style, loneliness, and social network as risk factors for late-life depression. METHODS: This cross-sectional study examined 969 subjects of the KORA-Age study. We applied the Relationship-Specific Attachment Scales for Adults (Beziehungsspezifische Bindungsskalen für Erwachsene, BBE), the UCLA Loneliness Scale, and the Social Network Index (SNI). Depression was operationalized through the Geriatric Depression Scale (GDS-15) and/or use of antidepressants. Logistic-regression models were calculated, sex-stratified, and controlled for age and living status. RESULTS: For men, lower depression scores were associated with higher attachment security scores (OR = 0.26, 95% CI = 0.15-0.44) and not reporting feelings of loneliness (OR = 0.27, 95% CI = 0.14-0.53). For women, independent determinants of not having late life depression consist of not feeling lonely (OR = 0.22, 95% CI = 0.13-0.38). DISCUSSION: Loneliness is a risk factor for late life depression in women and men, attachment style is a risk factor more for men, while social network size is not a risk factor.

No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.

Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.

Relationship between posttraumatic stress disorder and type 2 diabetes in a population-based cross-sectional study with 2970 participants.

OBJECTIVES: To evaluate the association of posttraumatic stress disorder (PTSD) with type 2 diabetes (T2D) or prediabetes in a large population-based sample. METHODS: In 2970 subjects (aged 32-81 years) drawn from the population-based cross-sectional study KORA F4 from the Augsburg region (Southern Germany) a PTSD screening was performed employing the posttraumatic diagnostic scale, the impact of event scale, and interview data. The exposure variable PTSD was sub-classified into partial and full PTSD and additionally in subjects with traumatic event but no PTSD" to "The exposure variable PTSD was classified into (1) no traumatic event (2) traumatic event, but no PTSD, (3) partial PTSD, (4) full PTSD. A total of 50 (1.7%) subjects qualified for full PTSD, whereas 261 (8.8%) qualified for partial PTSD. A total of 333 subjects (11.2%) suffered from T2D and 498 (16.8%) from prediabetes as assessed by an oral glucose tolerance test and physicians' validation. The associations of PTSD with T2D and prediabetes were estimated by multinomial logistic regression analyses with adjustments for sociodemographic characteristics, metabolic risk factors or psychopathological conditions. RESULTS: In the model adjusted for sociodemographic characteristics and metabolic risk factors, full PTSD was significantly associated with T2D (OR: 3.90, 95% CI: 1.61-9.45, p=0.003) compared to subjects with no traumatic event. Significance remained after additional adjustment for other psychopathological conditions (OR: 3.56, 95% CI: 1.43-8.85, p=0.006). Regarding prediabetes, no significant associations were observed. CONCLUSIONS: Suffering from PTSD might activate chronic stress symptoms and trigger physiological mechanisms leading to T2D. Prospective studies are needed to investigate temporal and causal relationships between PTSD and T2D.

Lifetime traumatic experiences and their impact on PTSD: a general population study.

OBJECTIVE: Exploring the relationship of exposure to a traumatic event and the subsequent onset of posttraumatic stress disorder (PTSD) in the population. METHODS: Posttraumatic stress disorder was assessed using the Impact of Event Scale (IES), Posttraumatic Diagnostic Scale (PDS) and interview data. Logistic regression analyses with sex, age, marital status, educational level and traumatic event characteristics were performed. Prevalences were standardised to the sex and age distribution of the German population. RESULTS: A total of 41 % of the subjects reported exposure to a trauma, leading to full PTSD in 1.7 % and to partial PTSD in 8.8 % of the participants. Logistic regression revealed accidents (OR 2.5, 95 % CI 1.3-4.7), nonsexual assault by known assailants (4.5, 2.1-9.8), combat/war experiences (5.9, 2.0-17.4), life-threatening illness (4.9, 2.7-8.9) and interpersonal conflicts (15.5, 2.5-96.0) as risk factors for full PTSD; risk factors for partial PTSD were accidents (3.2, 2.4-4.3), sexual (4.6, 2.2-9.6) or nonsexual (2.3, 1.4-3.8) assault by known assailants, life-threatening illness (6.2, 4.6-8.3), death of relatives (5.0, 3.2-7.8) and interpersonal conflicts (22.0, 8.3-58.1). CONCLUSIONS: Of subjects exposed to traumatic events, only a minority developed PTSD indicating a relationship between characteristics of the exposure and the individual and the onset of PTSD.

Relation between depressed mood, somatic comorbidities and health service utilisation in older adults: results from the KORA-Age study.

BACKGROUND: prior literature suggests that comorbidity with depression significantly worsens the health state of people with chronic diseases. OBJECTIVE: the present study examines whether depressed mood increased medical care use for patients with a comorbid physical disease. DESIGN, SETTING AND SUBJECTS: the study was a population-based study (KORA-Age), with 3,938 participants aged 64-94. METHODS: we investigated differences in health services use in participants with and without depressed mood (Geriatric Depression Scale). A further adjustment for disease was done and differences were examined with the Mann-Whitney U test. The incidence rate ratios (IRRs) for doctors' appointments or the number of days in hospital were explored with (zero-inflated) negative binomial regression models. RESULTS: there are increased self-neglecting behaviours and medical comorbidities in participants with depressed mood. Depressed mood increased participants' use of medical services (P < 0.0001). Among participants who visited the doctor during the last 3 months, those with depressed mood had more visits than those without depressed mood, irrespective of somatic comorbidities (P < 0.0001 and P < 0.05 for ill and healthy, respectively). Additionally, patients with coexisting depressed mood and physical disease visited the doctor's practice significantly more often. Having depressed mood significantly increases the likelihood for more doctor visits (IRR = 1.5, CI = 1.3-1.7) and longer hospital stays (IRR = 1.9, CI = 1.6-2.3). In participants with somatic comorbidities the risk is even greater (IRR = 1.6, CI = 1.3-2, for the number of doctors visits and IRR = 2, CI = 1.4-2.9, for the number of days in the hospital). CONCLUSIONS: results suggest that patients with depressed mood had increased use of health-care services overall, particularly those with somatic comorbidities.