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Biomedical subjects

A Hofman

Publications and source records attributed to A Hofman.

At least 19 recordsLinked to original sources

Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein. METHODS: We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures in these women. RESULTS: As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P=0.003) and the lumbar spine (P=0.02); the 58 women with the ss genotype had reductions of 4 percent at the femoral neck (P= 0.05) and 6 percent at the lumbar spine (P=0.005). These differences increased with age (P=0.01 for modification by age of the effect of COLIA1 on femoral-neck bone density, and P=0.004 for modification of the effect on lumbar-spine bone density). Women with the Ss and ss genotypes were overrepresented among the 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). CONCLUSIONS: The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Age Factors

Incidence and risk of dementia. The Rotterdam Study.

To assess age-, sex-, and subtype-specific incidence rates of dementia and to calculate the risk of dementia, the authors performed a large, community-based, prospective cohort study on dementia as part of the Rotterdam Study. Participants were recruited among residents of a suburb of Rotterdam, aged 55 years and older. Baseline examinations took place between 1990 and 1993. The average follow-up was 2.1 years. Screening for dementia followed a three-stage protocol. Medical records of subjects who had died or could not be examined in person were evaluated. Of 7,046 subjects who were nondemented at baseline, 162 developed dementia during 15,135 person-years of follow-up, resulting in an overall incidence rate of 10.7 per 1,000 person-years. From the youngest to the oldest 5-year age category, the incidence rate increased from 0.6 to 97.2 per 1,000 person-years. Only in men did the increase level off after age 85. Overall, the incidence rate per 1,000 person-years was 7.7 for Alzheimer's disease and 1.5 for vascular dementia. Dementia incidence rates and dementia-free Kaplan-Meier survival tables were used to calculate age- and sex-specific cumulative risks of dementia. Although the incidence rates of men and women up to age 85 were similar, the lifetime risk of dementia for 55-year-old women was twice as high as for men (0.33 vs. 0.16), reflecting both the higher life expectancy of women and the higher dementia risk at very old age.

Age Distribution

QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study.

BACKGROUND: Increased QTc dispersion has been associated with an increased risk for ventricular arrhythmias and cardiac death in selected patient populations. We examined the association between computerized QTc-dispersion measurements and mortality in a prospective analysis of the population-based Rotterdam Study among men and women aged > or = 55 years. METHODS AND RESULTS: QTc dispersion was computed with the use of the Modular ECG Analysis System as the difference between the maximum and minimum QTc intervals in 12 and 8 leads (ie, the 6 precordial leads, the shortest extremity lead, and the median of the 5 other extremity leads). After exclusion of those without a digitally stored ECG, the population consisted of 2358 men and 3454 women. During the 3 to 6.5 years (mean, 4 years) of follow-up, 568 subjects (9.8%) died. The degree of QTc dispersion was categorized into tertiles. Data were analyzed using the Cox proportional hazards model, with adjustment for age. For QTc dispersion in 8 leads, those in the highest tertile relative to the lowest tertile had a twofold risk for cardiac death (hazard ratio, 2.5; 95% confidence interval [CI], 1.6 to 4.0) and sudden cardiac death (hazard ratio, 1.9; 95% CI, 1.0 to 3.7) and a 40% increased risk for total mortality (hazard ratio, 1.4; 95% CI, 1.2 to 1.8). Additional adjustment for potential confounders, including history of myocardial infarction, hypertension, and overall QTc, did not materially change the risk estimates. Hazard ratios for QTc dispersion in 12 leads were comparable to those found for QTc dispersion in 8 leads. CONCLUSIONS: QTc dispersion is an important predictor of cardiac mortality in older men and women.

Age Factors

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease.

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.

Aged

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

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

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

Prolonged QT interval: a tricky diagnosis?

Prolonged heart-rate adjusted QT intervals on the electrocardiogram (ECG) are associated with an increased risk for coronary heart disease and sudden death. However, the diagnosis of the prolonged QT interval is hampered by lack of standards. We studied variations in the prevalence of prolonged QT, based on different common definitions, in a large nonhospitalized population, and compared our results with other studies applying the same definitions. The study population consisted of 2,200 men and 3,366 women participants of the Rotterdam Study, > or =55 years old. The QT interval was computed by our Modular ECG Analysis System (MEANS). Three different formulas to adjust QT for heart rate were used: Bazett's formula (QTc), a linear regression equation (QTlr), and the QT index (QTI). Prolonged QT occurred frequently in both men and women, and its prevalence increased with age. Women had longer heart-rate adjusted QT intervals than men (mean QTc 433 ms vs 422 ms), and mean values for QTlr were lower than for QTc (mean QTlr 422 ms in women and 412 ms in men). Prevalence was highest for prolonged QTlr (31% in men and 26% in women) and lowest for prolonged QTI (6% in men and 9% in women). Comparison with other studies applying the same correction formulas showed large discrepancies in prevalence estimates of prolonged QTc and QTlr, and to a lesser degree of prolonged QTI, possibly due to differences in measurement techniques. Future research is needed to relate QT interval to prognosis, to obtain measurement technique specific reference values of heart-rate adjusted QT measurements, and to obtain age- and sex-specific threshold values for prolonged QT. Such data are needed to use the QT interval with confidence.

Aged

Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study.

BACKGROUND: Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. METHODS AND RESULTS: We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. CONCLUSIONS: The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.

Aged

Psycho-education in bipolar disorder: effect on expressed emotion.

In a waiting-list controlled study on a multi-family psycho-educational intervention in bipolar disorder, key relatives in the treatment group showed a significant change from high to low levels of expressed emotion (EE) compared with the control group. In addition, patients with low-EE key relatives had a significantly lower number of hospital admissions compared with those living with high-EE key relatives. The multi-family groups were well received by the participants, and there were only a few drop-outs.

Adult

Bone density and risk of hip fracture in men and women: cross sectional analysis.

OBJECTIVE: To determine the relative contribution of decline in bone density to the increase in risk of hip fracture with age in men and women. DESIGN: Incidence data of hip fracture from the general population were combined with the bone density distribution in a sample from the same population and with a risk estimate of low bone density known from literature. SETTING: The Netherlands. SUBJECTS: All people with a hospital admission for a hip fracture in 1993, and bone density measured in a sample of 581.4 men and women aged 55 years and over in a district of Rotterdam. MAIN OUTCOME MEASURE: One year cumulative risk of hip fracture by age, sex, and bone density measured at the femoral neck. RESULTS: A quarter of all hip fractures occurred in men. Men reached the same incidence as women at five years older. Controlled for age, the risk of hip fracture by bone density was similar in men and women. The risk of hip fracture increased 13-fold from age 60 to 80; decrease in bone density associated with age contributed 1.9 (95% confidence interval 1.5 to 2.4) in women and 1.6 (1.3 to 1.8) in men. CONCLUSIONS: The risk of hip fracture by age and bone density is similar in men and women. The decrease in bone density associated with age makes a limited contribution to the exponential increase of the risk of hip fracture with age.

Age Factors

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample (n = 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association.

Aged

Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam Study.

BACKGROUND: Impaired fibrinolytic capacity, as assessed by euglobulin clot lysis time or plasma concentration of fibrinolytic parameters, has been associated with an increased risk of myocardial infarction (MI). We studied the association of a polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and activity) with the prevalence of MI. METHODS AND RESULTS: A case-control study was performed. Subjects with a history of MI (n = 121) and controls (n = 250) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects > or = 55 years old. We determined TPA antigen and activity in plasma and genotyped all subjects for the Alu repeat insertion/deletion polymorphism in intron h in the TPA gene. Homozygosity for the insertion was associated with twice as many cases of MI as was homozygosity for the deletion (odds ratio, 2.24; 95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI; compared with that in the lowest quartile, the relative risks (odds ratio) in the second, third, and upper quartiles were 1.7 (CI, 0.9-3.3), 2.3 (1.2-4.4), and 2.0 (1.0-3.8), respectively. When adjusted for body mass index, HDL and total cholesterol, systolic and diastolic blood pressures, and current smoking, the risk associated with TPA antigen concentration was attenuated. Increased concentrations of TPA activity tended to be associated with an increased risk of MI. CONCLUSIONS: This study provides evidence for an independent association of the insertion allele of the insertion/deletion polymorphism in the TPA gene with nonfatal MI. Increased TPA antigen is associated with an increased risk of MI; however, this association was not independent of cardiovascular disease risk factors.

Aged

Families and natural history of lipids in childhood: an 18-year follow-up study.

The natural history of total cholesterol and lipoprotein cholesterol in offspring was studied in relation to total cholesterol levels in their parents in the Epidemiological Prevention Study of Zoetermeer (EPOZ). All residents of 5 or more years who were living in two districts in the Dutch town of Zoetermeer were invited to participate in a study on indicators for chronic diseases between 1975 and 1978. In a random sample of 483 youngsters who were 5-19 years old, yearly measurements of cardiovascular risk factors were performed during a follow-up period of 18 years (average follow-up, 13.8 years). Total and subfraction cholesterol levels in offspring during follow-up were studied by tertiles of age-adjusted total cholesterol in their parents. Total and low density lipoprotein (LDL) cholesterol levels measured from childhood into young adulthood differed significantly between offspring whose fathers were in the highest total cholesterol tertile compared with those whose fathers were in the lowest tertile, amounting to 0.4 mmol/liter for total cholesterol and 0.5 mmol/liter for LDL cholesterol. Offspring differences by maternal tertiles amounted to 0.5 mmol/liter for total cholesterol and 0.6 mmol/liter for LDL cholesterol. Offspring (n = 53) with both parents in the upper cholesterol tertile had almost 1 mmol/liter higher cholesterol levels compared with offspring (n = 51) with both parents in the lowest tertile, whereas offspring (n = 48) with both parents in the middle tertile had intermediate levels. Differences remained after adjustment for sex, Quetelet index, systolic and diastolic blood pressure, and use of alcohol, cigarettes, and oral contraceptives. Offspring group differences in total and LDL cholesterol were already present in childhood and persisted into young adulthood. There was no clear relation between offspring change in cholesterol levels and parental total cholesterol levels. For high density lipoprotein cholesterol and its subfractions, no relations with parental total cholesterol levels were found. Based on the evidence of a strong positive relation between total cholesterol levels in parents and offspring levels of total and LDL cholesterol measured from childhood into young adulthood, the authors conclude that total and LDL cholesterol levels in offspring may already be characterized from young age and beyond through cholesterol levels in their parents.

Adolescent

Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation.

OBJECTIVE: To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). DESIGN AND SETTING: Population-based, case-control study from Rotterdam, the Netherlands, and New York City. PARTICIPANTS: A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. MAIN OUTCOME MEASURES: The APOE allele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to the APOE epsilon4 allele. RESULTS: Overall, patients with dementia and stroke had a higher APOE epsilon4 allele frequency than controls. Compared with APOE epsilon3 homozygote individuals, APOE epsilon4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), while APOE epsilon4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated with APOE epsilon4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to the APOE epsilon4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD. CONCLUSION: The APOE epsilon4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.

Aged

Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study.

BACKGROUND: Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. METHODS: We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls. FINDINGS: All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001). INTERPRETATION: These findings suggest that dementia and its two major subtypes Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.

Aged

Usefulness of echocardiography in detecting left ventricular dysfunction in population-based studies (The Rotterdam Study).

In a population-based study, the routine 12-lead electrocardiogram was found to have a high negative predictive value for detecting left ventricular (LV) systolic dysfunction. Withholding echocardiography in persons without major electrocardiographic abnormalities, however, would result in a considerable underestimation of LV systolic dysfunction (sensitivity only 54%); thus, echocardiography remains an essential tool for detecting LV systolic dysfunction in population-based studies.

Echocardiography, Doppler

Diabetes mellitus, impaired glucose tolerance, and hyperinsulinemia in an elderly population. The Rotterdam Study.

To estimate the prevalence of glucose intolerance in the elderly, oral glucose tolerance tests were performed as part of the Rotterdam Study, a population-based study in subjects aged 55 years and over. The study population consisted of 2,668 men and 3,950 women. Diabetes mellitus was defined as the use of antidiabetes medication, or a random or post-load serum glucose level of > or = 11.1 mmol/liter. Impaired glucose tolerance was defined as a post-load serum glucose between 7.8 and 11.1 mmol/liter. In men, the frequency of diabetes mellitus ranged from 5.9% in ages < 60 years to 19.8% in ages > 85 years, and in women from 3.8% in ages < 60 years to 18.9% in ages > 85 years; more than half of the subjects with diabetes were newly diagnosed. The prevalence of impaired glucose tolerance ranged from 8.8% and 11.0% in men and women aged < 60 years to 24.3% and 34.7% in men and women aged > 85 years. The prevalence of diabetes mellitus in the total Rotterdam Study population of 7,439 elderly men and women was estimated to be 11.3% (95% confidence interval (CI) 10.5-12.0). Waist/hip ratio, systolic blood pressure, hypertension, and number of cigarettes smoked increased with a worsening of the glucose tolerance from normal, hyperinsulinemia, impaired glucose tolerance to diabetes in both men and women (p < 0.01, adjusted for age). Body mass index was higher in subjects with glucose intolerance, but the frequency of obesity showed a relative decrease with worsening of glucose tolerance. These results show that glucose intolerance, especially impaired glucose tolerance and undetected diabetes mellitus, is common in the elderly. Moreover, not only subjects with diabetes mellitus but also subjects with hyperinsulinemia and impaired glucose tolerance have an increase of cardiovascular risk factors.

Age Distribution