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JA Janssen, H Burger, RP Stolk, DE Grobbee, FH de Jong, SW Lamberts and HA Pols

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.

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AW van den Beld, WF Blum, HA Pols, DE Grobbee and SW Lamberts

BACKGROUND: In a cross-sectional study in 403 healthy, independently living elderly men (mean age 78 years), we determined which are the main physiological determinants of functional ability in the elderly, and which components of the somatotropic system contribute to the maintenance of functional ability. METHODS: Functional ability was assessed by the number of problems in activities of daily living and by a measure of physical performance. Other physical characteristics included leg extensor strength, bone mineral density of total body and proximal femur, and body composition, including lean mass and fat mass. Serum insulin-like growth factor (IGF)-I and its binding proteins (IGFBP) -1, -2 and -3 concentrations were all measured by RIA. RESULTS: Muscle strength was related to a lower degree of disability. Further, it was positively related to physical performance and bone mineral density (all P<0.001). Fat mass influenced activities of daily living and physical performance negatively and bone mineral density positively (all P<0.001). Serum concentrations of IGF-I and IGFBP-3 were not related to any of the physical characteristics. High serum IGFBP-2 concentrations were related to a higher degree of disability (P<0.001), a lower physical performance (P=0.006), muscle strength (P=0.002), bone mineral density of proximal femur (P=0.007), lean mass and fat mass (both P<0.001). Serum insulin and IGFBP-1 concentrations were independently, positively related to lean mass (P=0.003) and fat mass (P<0.001). CONCLUSIONS: In independently living elderly men, functional ability appears to be determined by muscle strength (positive) and fat mass (negative). Low serum IGFBP-2 concentrations are a powerful indicator for overall good physical functional status, probably inversely reflecting the integrated sum of nutrition and the biological effects of growth hormone, IGF-I and insulin.

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M Muller, I den Tonkelaar, JH Thijssen, DE Grobbee and YT van der Schouw

OBJECTIVE: To determine the relationship between aging, life-style factors and health-related factors and endogenous sex hormone levels. DESIGN: Cross-sectional study of 400 independently living men between 40 and 80 Years of age. METHODS: After exclusion of subjects who were not physically or mentally able to visit the study center, 400 men were randomly selected from a population-based sample. Total testosterone (TT), bioavailable testosterone (BT) (i.e. not bound to sex hormone-binding globulin (SHBG)), SHBG, estradiol (E(2)) and dehydroepiandrosterone-sulfate (DHEA-S) were investigated for their relationship with age, body mass index (BMI), waist circumference, smoking, physical activity and general health status. Multivariate models using ANCOVA analyses were used to examine the contribution of life-style factors to sex hormone variability. RESULTS: TT, BT and DHEA-S decreased with age; 0.2, 0.7 and 1.2%/Year respectively. SHBG showed an increase with age of 1.1%/Year. No changes with age were found for E(2). General health status modified the association of TT and SHBG with age (P interaction 0.10 and 0.002 respectively). Increased BMI and waist circumference were associated with decreased TT, BT, SHBG and DHEA-S and increased E(2) (all P<0.01). Current smoking, lower alcohol intake and a higher physical activity score were associated with higher TT and SHBG levels. CONCLUSION: This study showed the important determinants of sex hormones were age, BMI, waist circumference, smoking, general health status and physical activity. Furthermore, it can be concluded that general health status modified the effect between sex hormones and age. For future observational studies it should be taken into account that the above-mentioned determinants may alter the association between sex hormones and diseases and related conditions.

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Annet F M van Abeelen, Mariken de Krom, Judith Hendriks, Diederick E Grobbee, Roger A H Adan and Yvonne T van der Schouw


Uncoupling protein 3 (UCP-3) uncouples oxidative metabolism from ATP synthesis, resulting in the production of heat instead of energy storage. Single nucleotide polymorphisms (SNPs) in UCP-3 might result in a reduced function or expression of UCP-3 and therefore lead to an increased capacity to store energy as fat.


We conducted a population-based, cross-sectional single-center study among 400 Dutch men between 40 and 80 years.


Seven SNPs in the UCP-3 gene were genotyped by means of an allele-specific real-time TaqMan PCR. Linear regression analyses were performed to examine the independent effects of these SNPs on obesity phenotypes.


We found a significant association between homozygosity for the minor allele of rs647126, rs1685356, and rs2075577 and an increase in body mass index (BMI; P=0.033, P=0.016, and P=0.019 respectively). Heterozygosity for rs1685354 was associated with a significant decrease in visceral fat mass (P=0.030).


Our results suggest that genetic variations in the UCP-3 gene are associated with an increase in BMI. A plausible mechanism by which these SNPs lead to an increase in BMI is that due to these SNPs, the UCP-3 activity might be decreased. As a result, uncoupling activity may also decrease, which will lead to an increase in body weight and BMI.

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Annet F M van Abeelen, Mariken de Krom, Judith Hendriks, Diederick E Grobbee, Roger A H Adan and Yvonne T van der Schouw

The authors and the journal apologize for an error in the above paper which appeared in 158 (5) 669–676. In this paper, on page 671, the fifth sentence should appear as follows ‘Each mixture consisted of 1 μl (8 ng) genomic DNA, 0.125 μl 40* assay mix (Applied Biosystems), and 2.5 μl TaqMan Universal Master Mix (Applied Biosystems)’.