Biomedical subjects

D E Grobbee

Publications and source records attributed to D E Grobbee.

At least 253 records · Page 14Linked to original sources

PubMed1998

Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people.

The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation factor VII clotting activity (FVII:C) are associated with the risk of myocardial infarction; nutrition may have an effect on these levels if people are genetically susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and the extreme quintiles of the FVII:C distribution were selected for measurement of the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158 subjects, habitual diet was assessed with a semiquantitative food-frequency questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09 in the highest quintile. The quintiles were combined for linear regression analyses. FVII:C was inversely associated with fiber [beta = -0.64 %pooled plasma (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (beta = -0.16 %PP/g, CI: -0.31,-0. 01) and positively with saturated fat intake (beta = 0.19 %PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (beta = -0. 38 %PP/g, CI: -0.71,-0.05). No other associations with diet were observed. The inverse association of FVII:C with fiber was stronger in subjects with the RR genotype (beta = -0.76 %PP/g, CI: -1.23,-0. 29), than in those with the RQ/QQ genotypes (beta = -0.19 %PP/g, CI: -0.97,0.59). The same was found for FVII:Chr. The association of FVII:C with saturated fat was positive in those with the RR allele and inverse in those carrying the Q allele. These findings suggest that the strength of the association between coagulation factor VII and diet varies across the genotypes of the R/Q353 polymorphism.

Aged↗

PubMed1998

Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.

OBJECTIVE: To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. DESIGN: A double-blind randomized, placebo-controlled trial. SETTING: General practitioners referred patients to the trial physician. PATIENTS: The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. INTERVENTION: Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. MAIN OUTCOME MEASURES: The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. RESULTS: Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). CONCLUSION: These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

Aged↗

PubMed1998

Hypertension, antihypertensive drugs, and mortality from cancer among women.

OBJECTIVES: To investigate whether hypertension and the use of antihypertensive drugs are associated with mortality from cancer among women. DESIGN: A prospective study of 11075 women living in Utrecht, the Netherlands, aged 50-65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985, during which blood pressure measurements were taken and information on drug use and smoking was ascertained. Since 1974 (median follow-up time 19 years) information on cause of death has been obtained from the patient's general practitioner. Hypertension was defined as a systolic blood pressure > 160 mmHg, a diastolic blood pressure > 95 mmHg, or current use of antihypertensive drugs. Cox regression analysis was used to investigate the association between hypertension (treated and untreated) and total and site-specific mortalities from cancer. The influences of systolic and diastolic blood pressures per 10 mmHg increase for women not using antihypertensive drugs were evaluated. Analyses were adjusted for age, smoking, and body mass index. RESULTS: In total, 704 women died of cancer and 1633 women left the study area. Hypertensive women had a greater than normal (not statistically significant) total risk of mortality from cancer [hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.93-1.31]. Risks for treated and untreated hypertensive women were similar. Cancer-site-specific analyses revealed a statistically significantly lower mortality from gastrointestinal cancers among untreated hypertensive women (HR 0.64, 95% CI 0.44-0.93), whereas mortality from lung cancer was more prevalent among these women (HR 2.50, 95% CI 1.37-4.59). Mortality from lymphatic and hematopoietic cancers for drug-treated hypertensive women was greater than normal (HR 2.11, 95% CI 1.04-4.28), as was mortality from cancers of the uterus, cervix, and ovary (HR 1.80, 95% CI 1.00-3.26). CONCLUSION: These results support the hypothesis that, if there is a link between blood pressure and cancer, it is likely to be positive and relatively small (+10%); and applies also to nondrug-treated women. The relation may apply for some types of cancer, but not for others.

Aged↗

PubMed1998

Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study.

OBJECTIVE: To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function. METHODS: During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis. RESULTS: The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women). CONCLUSIONS: Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability.

Age Factors↗

PubMed1998

Prevention of relapse in patients with congestive heart failure: the role of precipitating factors.

Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF.

Alcohol Drinking↗

PubMed1998

Minor disease features in neurofibromatosis type 1 (NF1) and their possible value in diagnosis of NF1 in children < or = 6 years and clinically suspected of having NF1. Neurofibromatosis team of Sophia Children's Hospital.

OBJECTIVE: To establish the frequency of minor disease features in children with neurofibromatosis type 1 (NF1) and to evaluate the value of minor disease features in children < or = 6 years with a suspected diagnosis of NF1, considering that the disease is virtually 100% penetrant at 6 years of age. DESIGN: During this 10 year, prospective, multidisciplinary, follow up study, 209 children suspected of having NF1 were examined; 150 were diagnosed with NF1 and 59 were not. The present analysis included children in whom NF1 was considered to be present at 6 years of age (n=85) and children without NF1 at 6 years of age (n=42). RESULTS: The minor disease features macrocephaly (52.9%), short stature (24.7%), hypertelorism (63.5%), and thorax abnormalities (37.6%) were highly prevalent in children with NF1 and significantly associated with a diagnosis of NF1 at 6 years of age. In addition, the mean number of minor disease features was significantly higher in children with NF1 at 6 years of age compared to the group without a diagnosis at 6 years of age (mean 1.8 v 0.8, p<0.001). Moreover, children with three or more minor disease features were all diagnosed with NF1 under the age of 6 years. Multivariate analysis using a logistic regression model showed that macrocephaly, short stature, hypertelorism, and thorax abnormalities were all independently associated with the presence of NF1 at 6 years of age. CONCLUSION: In children with insufficient diagnostic criteria aged < or = 6 years, documentation of minor disease features may be a helpful aid in predicting the diagnosis of NF1 in years to come.

Adolescent↗

PubMed1998

Differences in observer variability of ultrasound measurements of the proximal and distal abdominal aorta.

OBJECTIVE: To assess the observer variability of ultrasound measurements of the abdominal aorta and to study whether observer variability is influenced by the site of measurement or cardiovascular risk factors. SETTING: Population based screening programme for abdominal aortic aneurysms. METHODS: For 135 subjects taking part in a screening programme for abdominal aortic aneurysms, two of the three ultrasonographers measured the distal and proximal ultrasound diameter of the abdominal aorta, using B-mode ultrasound, according to the Rotterdam study scanning protocol. RESULTS: The mean difference between two different observers was 0.06 mm (95% CI-0.15 to 0.27) for measurements of the distal aorta and 0.32 mm (95% CI 0.09 to 0.55) for the proximal aorta. Maximal differences between observers for measurements of both the distal and proximal aortic diameter were 4.0 mm. Interobserver variability in the proximal and distal measurements of the abdominal aorta was not related to the level of the major cardiovascular risk indicators. However, interobserver variability in ultrasound measurements of the proximal aorta increased with increasing waist circumference and increasing diameter of the proximal aorta. CONCLUSION: Ultrasonographic readings of the distal and proximal aortic measurements can be interpreted within a range of plus or minus 3 mm. Ultrasound measurements are more accurate for the distal than for the proximal measurement. Definition of the aortic diameter based on a combination of both distal and proximal measurement may be more accurate.

Aged↗

PubMed1998

Serum free and total insulin-like growth factor-I, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 Levels in healthy elderly individuals. Relation to self-reported quality of health and disability.

BACKGROUND: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. DESIGN: In a cross-sectional population based study of 218 healthy elderly subjects (age 55-80 yrs) fasting free and total insulin-like growth factor (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Subjective quality of health was assessed by asking all participants whether they judged the quality of their health as better, the same or worse than that of their peers. Disability was determined by the Disability Index of the Stanford Health Questionnaire. RESULTS: Mean serum-free IGF-I levels were significantly lower in the 21 subjects who experienced their health as worse than those of their peers, compared to the 181 subjects who experienced their health as better or the same as their peers 0.069 (SE 0.009) vs. 0.093 nmol/l (SE 0.004) (p = 0.04). Mean IGFBP-1 levels were significantly higher in subjects, who felt less healthy than their peers 1.23 (SE 0.26) vs. 0.73 nmol/l (SE 0.82) (p = 0.01). Free and total IGF-I, IGFBP-1 and IGFBP-3 levels, were not different in subjects with the lowest and the highest Disability Index Score. CONCLUSION: Low free IGF-I and high IGFBP-1 levels are associated with a decreased self-reported quality of health, but are not related to physical disability in the elderly.

Aged↗

PubMed1998

Quality of life in short adults.

The use of (costly) growth hormone (GH) treatment in short children is often justified by the assumption that short stature considerably reduces quality of life in adults. We tested this assumption in 5 groups of short adults: 25 patients with isolated GH deficiency; 17 male patients with childhood onset renal failure; 25 women with Turner syndrome and 26 patients who were presented as a child to a paediatrician for idiopathic short stature. A group of 44 short individuals with presumably idiopathic short stature, who had not been presented to a paediatrician for short stature, was sampled from the general population ('normal shorts'). We measured quality of life in terms of socio-economic variables, the Nottingham Health Profile and time trade-off. The mean height of most groups was close to the 3rd percentile. The chance of having a partner was low for all groups, except for the normal shorts. Problems with job application were only reported in Turner syndrome. The scores on the Nottingham Health Profile were all within the normal range, but GH-deficient adults had a higher score on the domain energy than normal shorts. Women with Turner syndrome, individuals with renal failure, and those with idiopathic short stature had a wish to be taller, with an estimated reduction in quality of life of 2-4% (time trade-off). As the normal shorts did not show any sign of a reduced quality of life, we falsify the assumption of a direct relation between short stature and quality of life. The complaints of patients with idiopathic short stature around the 3rd percentile seem to be the result of unsuccessful coping strategies.

Adolescent↗

PubMed1998

Peripheral arterial disease in the elderly: The Rotterdam Study.

To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC.

Age Distribution↗

PubMed1998

LDL oxidation and extent of coronary atherosclerosis.

Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case subjects and hospital control subjects were selected from subjects undergoing a first coronary angiography. Subjects with severe coronary stenosis (> or = 85% stenosis in one and > or = 50% stenosis in a second major coronary vessel) were classified as case subjects (n=91). Hospital control subjects with no or minor stenosis (< or = 50% stenosis in no more than two of the three major coronary vessels, n=94) and population control subjects free of plaques in the carotid artery (n=85) were pooled for the statistical analysis into one control category. Enrollment procedures allowed for similar distributions in age and smoking habits. Case subjects had higher levels of total and LDL cholesterol and triglycerides and lower levels of HDL cholesterol. Resistance time, maximum rate of oxidation, and maximum diene production were measured ex vivo using copper-induced LDL oxidation. A borderline significant inverse trend was observed for coronary atherosclerosis risk at increasing resistance time. Odds ratios (95% confidence interval) for the successive quartiles were 1.0 (reference), 0.77 (0.39 to 1.53), 0.67 (0.33 to 1.34), and 0.55 (0.27 to 1.15) (ptrend=0.07). No relation with maximum rate of oxidation was found, and higher maximum diene levels were found in control subjects (P<.01). The main determinant of oxidation was the fatty acid composition of LDL. No effect of smoking or use of medication was observed. We conclude that although LDL resistance to oxidation may be a factor in atherogenesis, the ex vivo measure is not a strong predictor of severity of coronary atherosclerosis.

Aged↗

PubMed1998

Serum total IGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease.

Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (P=.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (P=.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (P=.02, adjusted for age and sex) and who had never smoked (P=.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis.

Aged↗

PubMed1998

Elevated plasma fibrinogen: cause or consequence of cardiovascular disease?

An association between increased plasma fibrinogen and an increased risk for myocardial infarction (MI) is well established, but the nature of this association is subject to debate. Our aim was to shed light on the potentially causal nature of this association. We examined whether increased plasma fibrinogen, due to a condition that is independent of cardiovascular events, also increases the risk for MI. A case-control study was performed in 139 subjects with a history of MI and 287 control subjects selected from the Rotterdam Study, a population-based cohort of 7983 subjects aged 55 years and older. The genotype of the -455G/A polymorphism in the fibrinogen beta-gene was determined by polymerase chain reaction. Functional plasma fibrinogen levels were determined according to von Clauss. The plasma level of fibrinogen was significantly higher in subjects with one or two A alleles compared with subjects with the GG genotype: 3.8 (95% confidence interval [CI], 3.6 to 3.9) g/L and 3.6 (3.5 to 3.7) g/L, respectively. With increasing plasma fibrinogen level, the risk for MI increased gradually; a rise in fibrinogen of 1 g/L was associated with a 45% increased risk (odds ratio adjusted for age, sex, and smoking, 1.45; 95% CI, 1.12 to 1.88). There was no association between the genotype of the -455G/A polymorphism and the risk for MI. The -455G/A polymorphism is therefore associated with increased plasma fibrinogen levels but not with an increased risk for MI. These findings indicate that an increased plasma fibrinogen level due to this genetic factor does not increase the risk for MI.

Aged↗

PubMed1998

The CAMCOG: a useful screening instrument for dementia in stroke patients.

BACKGROUND AND PURPOSE: Most mental screening tests focus on the detection of cognitive deficits compatible with Alzheimer's disease. Stroke patients who develop a dementia syndrome, however, constitute a more heterogeneous group with both cortical and subcortical disturbances. We assessed the diagnostic accuracy of the CAMCOG (the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly) and the Mini-Mental State Examination (MMSE) for dementia in patients with a recent stroke. METHODS: In patients aged 55 and older who were admitted in the Rotterdam Stroke Databank, cognitive functioning was assessed between 3 and 9 months after the most recent stroke. The "gold standard" diagnosis of dementia was compatible with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. The CAMCOG and MMSE scores were obtained independent of the diagnostic procedure. RESULTS: Of 300 consecutive patients, 71 (23.7%) were demented. Sixteen severely demented patients could not be tested and were excluded. The CAMCOG and MMSE scores were significantly related to dementia (both P<0.0001) in a logistic regression model. Receiver operating characteristic analysis showed that the CAMCOG was a more accurate screening instrument (area under the curve for CAMCOG, 0.95; for MMSE, 0.90). Two other clinical variables independently improved the diagnostic accuracy of the MMSE and CAMCOG: patients with a left hemispheric lesion had a lower (odds ratio, 0.3; 95% confidence interval, 0.1 to 0.7), and patients with hemorrhagic stroke had a greater chance of being demented (odds ratio, 3; 95% confidence interval, 1 to 10). The effect of left hemispheric lesion as an independent diagnostic factor could not be explained by selection or its association with aphasia alone. CONCLUSIONS: The CAMCOG is a feasible instrument for use in patients with a recent transient ischemic attack or stroke. It is a more accurate screening tool for dementia than the MMSE, especially when type and site of stroke are taken into account.

Aged↗

PubMed1998

A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo.

We investigated whether a polymorphism at nucleotide position 1220, resulting in an asparagine-to-serine change at codon 363 in the glucocorticoid receptor (GR) gene is associated with an altered sensitivity to glucocorticoids. In a group of 216 elderly persons, 13 heterozygotes for the N363S polymorphism were identified by PCR/single strand conformation polymorphism analysis. In 2 dexamethasone (DEX) suppression tests (DSTs), using 1 and 0.25 mg DEX, the circulating cortisol and insulin concentrations were compared between N363S carriers and controls. In the 1-mg DST, there were no differences between N363S carriers and controls, with respect to adrenal suppression, but there was a significantly higher (P < 0.05) insulin response in N363S carriers. In the 0.25-mg DST, a significantly larger (P < 0.05) cortisol suppression and higher (P < 0.05) insulin response were seen in N363S carriers. Comparison of blood pressure, body mass index (BMI), and bone mineral density (BMD) between the N363S carriers and controls showed that N363S carriers had a higher (P < 0.05) BMI but normal blood pressure. There was an obvious trend towards lower age-, BMI-, and sex-adjusted BMD in the lumbar spine in N363S carriers. GR characteristics measured in 41 controls and 9 N363S carriers in peripheral mononuclear leucocytes showed no differences between N363S carriers and controls, with respect to GR number and ligand binding affinity. However, there was a trend towards greater sensitivity to DEX in the carriers' lymphocytes, in a mitogen-induced cell proliferation assay. In transfection assays, the capacity of the codon 363 variant to activate mouse mammary tumor virus promotor-mediated transcription in COS-1 cells was unaltered, when compared with the wild-type GR. We conclude that in 6.0% of our study population, a polymorphism in codon 363 of the GR gene was found. Individuals carrying this polymorphism seemed healthy at clinical examination but had a higher sensitivity to exogenously administered glucocorticoids, with respect to both cortisol suppression and insulin response. Life-long exposure to the mutated allele may be accompanied by an increased BMI and a lowered BMD in the lumbar spine but does not affect blood pressure.

Aged↗

PubMed1998

Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals.

In the present study, we investigated whether the negative feedback action of glucocorticoids (GCs) on the hypothalamo-pituitary-adrenal (HPA) axis changes with age. We performed a 1-mg dexamethasone (DEX) suppression test in 216 healthy elderly individuals. To investigate individual variability of feedback sensitivity in more detail, 2.5 yr later a 0.25-mg DEX suppression test was carried out in 164 of the same individuals. We investigated whether there was an effect of age or gender on both basal and post-DEX cortisol levels, as well as on the concentration of DEX. Furthermore, we examined whether the reactions to the two doses of DEX differed, and whether indications for an intraperson stability of baseline cortisol levels could be found. Neither the pre- nor the post-1-mg DEX plasma cortisol concentrations showed a correlation with age, and there were no differences between men and women. The same was true for the pre- and post-0.25-mg DEX cortisol concentrations. In reaction to 1 mg DEX, over 90% of the subjects investigated showed a cortisol suppression to levels below 50 nmol/L. After the administration of 0.25 mg DEX, there was a much wider range in post-DEX cortisol concentrations. After the administration of 1 mg DEX, there was a significant correlation between liver function parameters and plasma DEX concentrations in males, and there was a correlation between body mass index and plasma DEX concentration in females. Plasma DEX concentrations after the administration of 1 mg and 0.25 mg DEX were closely correlated within subjects (P < 0.001). There was an intraindividual stability of serum cortisol levels determined at an interval of 2.5 yr. Furthermore, the individuals with the highest baseline cortisol concentrations also had the highest post-0.25-mg DEX cortisol concentrations, indicating a close relationship between basal cortisol levels and the feedback sensitivity of the HPA axis to a low dose of DEX. These observations suggest a genetic influence on the set point of the HPA axis. Aging does not seem to lead to a change in HPA activity as measured by early morning total cortisol levels. Also, no changes in the sensitivity of the feedback system to DEX were observed with age. DEX metabolism is influenced by liver function (in males) and by body mass index (in females).

Adult↗

PubMed1998

Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women.

OBJECTIVE: Little is known about the association between free IGF-I levels and bone mineral density (BMD). DESIGN: A cross-sectional study of 218 healthy subjects (103 men, 115 women, age 55-80 years) was carried out. METHODS: Fasting serum free IGF-I, total IGF-I, estradiol and sex hormone-binding globulin (SHBG) levels were measured. The ratio of estradiol to SHBG was used as an index of free estradiol. BMD measurements were performed by dual-energy X-ray absorptiometry of the lumbar spine and the proximal femur. RESULTS: In multivariate analyses with BMD of the lumbar spine as the dependent variable and serum free IGF-I, age, body mass index (BMI) and the free estradiol index as independent variables, the free IGF-I was positively related to the BMD of the lumbar spine in men (P = 0.02) but not in women. When the same analyses for the lumbar BMD were performed with total serum IGF-I the association was also only statistically significant in men (P = 0.05). In multivariate analyses with the trochanter BMD as the dependent variable and serum free IGF-I, total IGF-I, age, BMI and the free estradiol index as independent variables, the associations between (free and total) IGF-I and the trochanter BMD in men was of borderline significance. CONCLUSIONS: In elderly men free and total IGF-I were positively related to lumbar BMD, while (free and total) IGF-I was borderline positively related to trochanter BMD. As these relationships were not observed in elderly women, we suggest a weak gender-specific anabolic effect of IGF-I on BMD on trabecular bone.

Aged↗

PubMed1998

Fish oil and glycemic control in diabetes. A meta-analysis.

OBJECTIVE: Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials. RESEARCH DESIGN AND METHODS: Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects of fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F., M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design. RESULTS: All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: -0.60 mmol/l (95% CI, -0.84 to -0.33, P < 0.01) and a slight but significant increase in serum LDL cholesterol: 0.18 mmol/l (95% CI, 0.04-0.32, P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/l [95% CI, 0.00-0.87], P = 0.06) and were significantly lower in IDDM subjects (-1.86 mmol/l [95% CI, -3.1 to -0.61], P < 0.05). Significant dose-response effects of EPA (g/day) on HbA1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA1c, and triglycerides were demonstrated only in NIDDM subjects. CONCLUSIONS: The use of fish oil has no adverse affects on HbA1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

Blood Glucose↗