Genetics of serum dehydroepiandrosterone sulfate and its relationship to insulin in a population-based cohort of twin subjects

Previous studies have shown a significant effect of insulin administration on serum dehydroepiandrosterone sulfate (DHEA-S) concentration and its metabolic rate, with evidence for the effect in men, but not in women. This could lead to differences in the sources of variation in serum DHEA-S between men and women and in its covariation with insulin concentration. This study aimed to test whether these hypotheses were supported in a sample of healthy adult twins. Serum DHEA-S (n = 2287) and plasma insulin (n = 2436) were measured in samples from adult male and female twins recruited through the Australian Twin Registry. Models of genetic and environmental sources of variation and covariation were tested against the data. DHEA-S showed substantial genetic effects in both men and women after adjustment for covariates, including sex, age, body mass index, and time since the last meal. There was no significant phenotypic or genetic correlation between DHEA-S and insulin in either men or women. Despite the experimental evidence for insulin infusion producing a reduction in serum DHEA-S and some effect of meals on the observed DHEA-S concentration, there were no associations between insulin and DHEA-S at the population level. Variations in DHEA-S are due to age, sex, obesity, and substantial polygenic genetic influences.     

Relationship between self-assessed masticatory disability and 9-year mortality in a cohort of community-residing elderly people

OBJECTIVES: To examine the relationship between self-assessed masticatory disability and mortality. DESIGN: Prospective. SETTING: Community based. PARTICIPANTS: Total of 1,405 randomly selected people aged 65 and older living in Settsu, Osaka Prefecture, in October 1992. MEASUREMENTS: Data on health status as indicated by disability scores, history of health management, self-assessed masticatory ability, and psychosocial conditions were collected by means of interviews during home visits at the time of enrollment. Nine-year follow-up was completed for 1,245 (88.6%; 398 deceased and 847 alive). RESULTS: Self-assessed masticatory disability was significantly associated with being 75 and older, having overall disability, not using dental health checks or general health checks, not participating in social activities, not feeling that life is worth living (no ikigai), and finding relationships with people difficult. As for the association between self-assessed masticatory disability and mortality, the estimated survival rate for those with self-assessed masticatory disability was lower than that for those without for each group stratified by sex and age (65-74 and >or=75), and the equality of survival curves according to self-assessed masticatory disability was significant for each group. After controlling for potential predictors of mortality, self-assessed masticatory disability remained as a significant predictor of mortality (adjusted hazard ratio=1.63, 95% confidence interval=1.30-2.03, P<.001). CONCLUSION: These results indicate that self-assessed masticatory disability may be associated with a greater risk of mortality in community-residing elderly people.     

Plasma insulin-like growth factor I levels in the elderly: relation to plasma dehydroepiandrosterone sulfate levels, nutritional status, health and mortality.

BACKGROUND: Insulin-like growth factor I (IGF-I) has beneficial metabolic effects. Because plasma IGF-I levels have been reported to be enhanced by dehydroepiandrosterone (DHEA) administration, it has been suggested that the IGF-I may be implicated in some of the reported associations between low DHEA sulfate (DHEAS) levels and impaired health measures in elderly subjects. The nutritional status, which also regulates plasma IGF-I levels, is also an important determinant of health outcome. OBJECTIVE: We sought to investigate the associations between plasma IGF-I levels and plasma DHEAS levels, nutritional status, health, and mortality in the elderly. METHODS: In 256 community-dwelling subjects aged 65-101 years, enrolled in the Paquid study, a health questionnaire was used to acertain their functional disabilities, any history of medical disorders, self-perceived health, depressive symptoms, and their cognitive function. Biological measurements included levels of plasma IGF-I, albumin, transthyretin, and DHEAS. Mortality data were available for 6 years following blood sampling. RESULTS: In this elderly population with no impairment in nutritional status, the plasma IGF-I levels decreased significantly with age (p = 0.02). The plasma IGF-I levels correlated positively with those of transthyretin (p = 0.0001). IGF-I also correlated with DHEAS (p = 0.04), but the correlation did not remain significant after adjustment for age. As opposed to SDHEA, the plasma IGF-I levels did not correlate with the results from the health questionnaire. The baseline IGF-I values in the highest tertile were associated with a higher risk of short-term mortality than those in the lowest tertile (RR = 8.4 at 2 years, p = 0.007). CONCLUSIONS: Our results suggest that IGF-I is not connected with the association between low plasma DHEAS levels and the impaired results from the health questionnaire. The relationship between plasma IGF-I highest levels and mortality should be further explored.     

Cigarette smoking and cognitive impairment: A 10-year cohort study in Taiwan

The relationship between cigarette smoking and cognitive impairment is not a simple one. Some studies have demonstrated that cigarette smoking is a risk factor for cognitive impairment in the elderly, whereas other studies have shown cigarette smoking to be protective against dementia. This study aims to explore the relationship between cigarette smoking and cognitive impairment in elderly persons without dementia, during a 10-year period. Data were derived from a population-based cohort study of 1436 elderly Taiwanese. Cognitive function was measured by the SPMSQ both in 1993 and in 2003. A total of 1436 participants free of cognitive impairment at baseline (SPMSQ ≥ 6 in 1993) were included in these analyses. Subsequently, participants were divided into three groups: never, past, and current smokers. The effect of cigarette smoking on cognitive function was assessed using logistic regression. In the logistic regression model adjusted for age, education, hypertension, diabetes, heart disease, and stroke at baseline, persons who had quit smoking (Odds ratio = OR = 0.31; 95% CI = 0.18-0.53; p < 0.001) and those who continued to smoke (OR = 0.37; 95% CI = 0.20-0.70; p < 0.001) were about one-third as likely to develop cognitive impairment as were those who never smoked. However, no dose-response relationship was observed between pack-years and cognitive impairment. Past and current smokers were less likely to develop cognitive impairment during a 10-year follow-up than were those who had never smoked. The present study suggests that smoking may be protective for cognitive function.     

Risk factors for 6-year mortality by gender in a Japanese elderly population

The aim of this study is to examine gender differences in the factors associated with 6-year mortality among 784 elderly residents (mean age=73 years) in Japan from 1995 (baseline) to 2001. Survival status during 6 years of follow-up was confirmed by either inquiries of older participants or family members or data from official death certificates, or both in 2001. Information on variables associated with mortality was elicited by using a face-to-face interview at baseline (1995). Results of longitudinal analyses showed that self-rated health (SRH) was not an independent predictor of mortality among men or women after adjustment of the other factors. Instead of SRH, having much feeling of usefulness among men and being married among women were significantly associated with increased mortality risk, suggesting that these findings may play an important role in enhancing survival in the elderly.     

Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow-up study in a community-based cohort (Tanushimaru study)

OBJECTIVES: To determine whether serum dehydroepiandrosterone sulfate (DHEAS) levels could predict longevity in residents.
DESIGN: Prospective community-based cohort study.
SETTING: Community.
PARTICIPANTS: Nine hundred forty subjects (396 men, 544 women; aged 21 to 88) underwent a health examination in 1978. Serum DHEAS levels were measured according to radioimmunoassay at baseline in all subjects, and subjects were followed periodically until 2005.
RESULTS: Baseline DHEAS levels were higher in men than in women and decreased with age in both sexes. In a Cox proportional hazards model, age, DHEAS (inversely), blood pressure, and fasting plasma glucose were significantly associated with shorter longevity in men but not in women. Of these variables, high DHEAS levels in men were the strongest predictor of longevity (β=−2.032, hazard ratio=0.131, 95% confidence interval=0.029–0.584 in the Cox proportional hazards model after adjustment for age). The Kaplan-Meier survival curve, stratified according to tertiles of DHEAS levels, in men after adjustments for age, systolic blood pressure, and fasting plasma glucose showed significantly (log-rank stat =10.6; P <.001) greater longevity in the highest group (200 μg/dL) than in the moderate (130–199 μg/dL) or lowest groups (129 μg/dL).
CONCLUSION: This 27-year study in a community-based cohort indicated that DHEAS level may be a predictor of longevity in men, independent of age, blood pressure, and plasma glucose.     

Type 2 diabetes, smoking, insulin use, and mortality from hepatocellular carcinoma: a 12-year follow-up of a national cohort in Taiwan

Background

The effect of smoking and insulin use in the association between diabetes and hepatocellular carcinoma (HCC) is not known.

Materials and methods

Age-standardized HCC mortality trends during 1995–2006 in the general population were calculated. A total of 88,694 type 2 diabetic patients aged ≥25 years recruited in 1995–1998 were followed till 2006. Age- and sex-specific mortality rates and the mortality rate ratios (vs. the average mortality rates in the general population) were calculated. Risk factors were evaluated by Cox regression.

Results

The age-standardized mortality trend slightly increased significantly in women but was steady in men. For diabetic patients aged ≥25 years, 830 men and 515 women died of HCC during 1995–2006. Mortality rate ratios (95 % confidence interval) were larger with the decreasing age: 7.36 (6.52, 8.31), 2.48 (2.22, 2.78), 1.79 (1.59, 2.02), and 1.87 (1.51, 2.32) for age 25–54, 55–64, 65–74, and ≥75 years for men, respectively, 10.12 (7.73, 13.25), 4.08 (3.57, 4.67), 2.45 (2.15, 2.78), and 1.71 (1.34, 2.19) for women. Age, male sex, lower BMI, smoking, and insulin use were associated with HCC mortality, but diabetes duration was not. Smoking and insulin use carried a significantly higher risk of 22–29 % and 37–58 %, respectively, without interaction. A dose-responsive pattern between the duration of insulin use and HCC mortality was noted, with a relative risk of 1.5–1.7 in those who used insulin for ≥10 years.

Conclusions

Diabetic patients have a higher risk of HCC mortality, which is more remarkable in the younger age. Smoking and insulin are potentially modifiable risk factors.     

Discrimination ability of comorbidity,frailty, and subjective health to predict mortality in community-dwelling older people: Population based prospective cohort study

ObjectiveTo investigate the added value of comorbidity, frailty, and subjective health to mortality predictions in community-dwelling older people and whether it changes with increasing age.Participants36,751 community-dwelling subjects aged 50–100 from the longitudinal Survey of Health, Ageing, and Retirement in Europe.MethodsMortality risk associated with Comorbidity Index, Frailty Index, Frailty Phenotype, and subjective health was analysed using Cox regression. The extent to which health indicators modified individual mortality risk predictions was examined and the added ability to discriminate mortality risks was assessed.Main outcome measuresThree-year mortality risks, hazard ratios, change in individual mortality risks, three-year area under the receiver operating characteristic curve (AUC).ResultsThree-year mortality risks increased 41-folds within an age span of 50 years. Hazard ratios per change in health indicator became less significant with increasing age (p-value < 0·001). AUC for three-year mortality prediction based on age and sex was 76·9% (95% CI 75·5% to 78·3%). Information on health indicators modified individual three-year mortality risk predictions up to 30%, both upwards and downwards, each adding < 2% discriminative power. The added discrimination ability of all health indicators gradually declined from an extra 4% at age 50–59 to < 1% in the oldest old. Trends were similar for one-year mortality and not different between sexes, levels of education, and household income.ConclusionCalendar age encompasses most of the discrimination ability to predict mortality. The added value of comorbidity, frailty, and subjective health to mortality predictions decreases with increasing age.     

Clinical benefits of smoking cessation in reducing all-cause and disease-specific mortality among older people in Taiwan: A 10-year nationwide retrospective cohort study

ObjectiveTo investigate the relationship between smoking cessation and disease mortality risks among elderly Taiwanese.MethodsWe identified 1677 people aged 65 or above from the 2001 National Health Interview Survey in Taiwan (2001 NHIST) and linked with the 2000–2010 National Health Insurance Research Data (2000–2010 NHIRD) and 2001–2010 Death Registry. Subjects were classified into four groups: never smokers, current smokers, former smokers quitting less than 5 years and former smokers quitting at least 5 years. Information on medical history was drawn from 2000–2001 NHIRD. Cox proportional hazards models were used to analyze the smoking status and mortality risk.ResultsOver 10 years, incidences of all-cause death per person-year was 0.048 among the never smokers, 0.058 for current smokers and 0.057 for former smokers. Current smokers had higher risk of all-cause death (HR = 1.38, 95%CI = 1.13–1.68), all-cause cancers (HR = 1.85, 95%CI = 1.28–2.69), lung cancer (HR = 3.02, 95%CI = 1.56–5.85) and cardiovascular disease (HR = 1.71, 95%CI = 1.17–2.48) as compared to never smokers. Former smokers who quit smoking for < 5 years has higher mortality risk in lung cancer (HR = 3.89, 95%CI = 1.33–11.40), respiratory diseases (HR = 2.79, 95%CI = 1.32–5.87) and chronic obstructive pulmonary disease (COPD) (HR = 3.13, 95%CI = 1.07–9.17) as compared to never smokers. Former smokers who quit smoking for over 5 years were similar to never smokers on all-cause death, lung cancer, all-cause cancers, COPD, respiratory diseases and cardiovascular diseases.ConclusionSmoking plays a prominent role in increasing the mortality risk among the Taiwanese elderly. Disease mortality risks of elderly former smokers who quit smoking over 5 years were reduced to the same level as the never smokers.     

Co-morbidities and mortality associated with transfusion-dependent beta-thalassaemia in patients in England: a 10-year retrospective cohort analysis

A retrospective cohort analysis to explore 10-year mortality and prevalence of transfusion-dependent β-thalassaemia (TDT)-associated co-morbidities in patients with TDT was undertaken using Hospital Episode Statistics (HES) data from the National Health Service (NHS) in England. A 10-year forward-looking cohort analysis for the period 2009–2018 was completed using HES admitted patient care (APC), outpatient data, and linked HES/Office of National Statistics mortality data for patients with β-thalassaemia (ICD-10 diagnosis code D56.1). TDT-associated co-morbidity rates were high in the 612 patients with TDT, with 76% having at least one co-morbidity, 54% suffering from two of more, and 37% three or more. The three most common TDT-associated co-morbidities, occurring in more than one third of patients were: endocrine disorders (excluding diabetes) 40%, osteoporosis 40%, and diabetes 34%. Cardiac disease was observed in 18% of patients overall, with atrial fibrillation and heart failure being the most common with a prevalence of 11% and 9%, respectively. The crude 10-year mortality rate in the TDT cohort was 6·2% (38/612), significantly greater than the 1·2% age/sex-adjusted mortality rate of the general population (P < 0·001). These data support the notion that the unmet need in TDT remains significant, with high rates of co-morbidity and mortality.     

Gonadal and adrenal secretion of dehydroepiandrosterone sulfate in prepubertal and pubertal subjects

The Authors have evaluated the relationship between the secretion of dehydroepiandrosterone sulfate (DHA-S) by the adrenal glands and by the gonads in a group of prepubertal and pubertal subjects ("short normal"), both males and females. In the male subjects of a hCG test and an ACTH test were performed; in the female subjects only the latter test was carried out. The behavior of DHA-S under basal conditions was also assessed in both sexes and related to bone age and chronological age in the prepubertal period and during the early stages of puberty. Plasma levels of DHA-S in both sexes increase progressively with chronological age and bone age. A negative correlation was found between DHA-S and bone delay (expressed in percent relative to chronological age) in prepubertal subjects, both males and females. A significant increase in DHA-S after hCG stimulation was found both in prepubertal and pubertal boys. After ACTH stimulation DHA-S increased significantly in prepubertal and pubertal males and females; throughout the test no difference was found between prepubertal and pubertal subjects nor between male and female subjects. Our data confirm that DHA-S is produced both by the adrenals and by the testes.     

Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study

In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30–50% higher in men than in women) decreases with age, toward ≈20–10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such “treatment” are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.     

Blood pressure, smoking and body mass in relation to mortality from stroke and coronary heart disease in the elderly. A 10-year follow-up in Norway.

OBJECTIVES: To examine the association between blood pressure, smoking and body mass index (BMI) and cerebro- and cardiovascular mortality in a population of healthy elderly. DESIGN: Ten-year mortality follow-up of elderly men and women who participated in the Nord-Tr?ndelag Health Study 1984-86. SETTING: Nord-Tr?ndelag county, Norway. SUBJECTS: 3121 men and 3271 women aged 70 years and older, free from any diagnosed atherosclerotic diseases or diabetes at baseline. MAIN OUTCOME MEASURES: Relative risk of cerebro- and cardiovascular mortality and all-cause mortality according to blood pressure, smoking and BMI. RESULTS: There was a consistent, positive association between systolic and diastolic blood pressure and cerebro- and cardiovascular mortality. The association persisted after adjustment for potential confounding factors, and was strongest for cerebrovascular mortality; the adjusted relative risks for systolic blood pressure categories 160-179 mmHg and > or = 180 mmHg in men were 1.63 (95% confidence interval, CI 1.06-2.53) and 2.19 (95% CI 1.39-3.44) compared to blood pressure < 140 mmHg. In women, the corresponding relative risks were 1.54 (95% CI 0.93-2.56) and 2.12 (95% CI 1.29-3.50). For diastolic blood pressure the adjusted relative risks in categories 100-109 and > or = 110 mmHg in men were 1.88 (95% CI 1.19-2.95) and 3.06 (95% CI 1.79-5.21) compared to pressure <90 mmHg. The corresponding relative risks in women were 1.75 (95% CI 1.05-2.91) and 2.02 (95% CI 1.04-3.93). Current smoking increased cardiovascular mortality in both men and women, and among women, BMI was negatively associated with all-cause mortality. CONCLUSIONS: These findings add to the growing evidence that hypertension is a major risk factor for mortality from stroke and coronary heart disease among the elderly and the very old.     

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Obesity, physical activity, and mortality in a prospective chinese elderly cohort

BACKGROUND: In older people, it is unclear whether obesity relates to mortality, which calls into question its etiologic role in disease and its public health relevance. This apparent lack of relationship in older people could be an artifactual result of their diverse health states. METHODS: We used Cox regression analysis to determine whether the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) or physical activity on mortality varied with health status in a prospective cohort study of Chinese people 65 years or older enrolled from 1998 to 2000 at all of the 18 Elderly Health Centers of the Hong Kong Government Department of Health. Health status was categorized into 5 morbidity groups using a 12-item index covering illnesses, medications, frailty, and smoking. RESULTS: After a mean follow-up of 4.1 years, there were 3819 deaths in 54 088 subjects (96.5% successful follow-up). The effect of BMI on mortality varied with baseline health status (P<.001). In the healthiest group, obese people (BMI >/=25) had higher mortality (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.02-2.33), but in the unhealthiest group they had lower mortality (HR, 0.55; 95% CI, 0.49-0.63) compared with subjects of normal weight. Daily physical activity was associated with lower mortality compared with inactivity in the unhealthiest group (HR, 0.70; 95% CI, 0.61- 0.81) but not in the healthiest group. CONCLUSIONS: In the elderly, the relationship between obesity and mortality varies according to the underlying health status. In those with poor health status, obesity is associated with better outcome, whereas in those with initially good health status, obesity is associated with worse outcome.