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  • 1
    ISSN: 1433-2965
    Keywords: Key words:Broadband ultrasound attenuation – Quantitative ultrasound – Speed of sound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Quantitative ultrasound (QUS) assessment of bone is a strong predictor of hip fractures and is currently an FDA-approved tool to identify women at risk of osteoporosis. However, few studies have investigated the lifestyle and genetic correlates of QUS in women. This study investigated the cross-sectional associates of several lifestyle, demographic and genetic factors with calcaneal QUS parameters (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) in 393 women aged 45–53 years. Leisure-time and historical physical activity, dietary calcium and protein, body composition, vitamin D receptor genotypes, menopause status, other health behaviors, calcaneal QUS parameters and bone mineral density (BMD) were assessed at a single clinic visit. Lean mass, recent physical activity and African-American race were the strongest correlates of SOS whereas dietary protein, calcium and recent physical activity were the strongest correlates of BUA. These predictors explained 13% and 6% of the variance in SOS and BUA, respectively. Smoking, alcohol intake, education, hormone replacement therapy, calcium and vitamin D supplements, historical physical activity and vitamin D receptor genotypes were not significantly associated with BUA or SOS. Lean body mass and premenopausal status were the strongest correlates of lumbar BMD whereas lean body mass, physical activity, African-American race and body mass index were significantly related to femoral neck BMD. Physical activity remained predictive of SOS after controlling for lumbar BMD. The spectrum and magnitude of risk factors for SOS and BUA, including lean body mass, physical activity, race, protein and calcium intake, parallel previously observed predictors of BMD.
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  • 2
    ISSN: 1433-2965
    Keywords: Bone mineral density ; Osteoporosis ; Premenopausal ; Vitamin D receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The genetic influence on bone mineral density (BMD) is thought to be mediated in part by alleles at the vitamin D receptor (VDR) locus. In order to assess the effect of VDR on BMD in premenopausal women, we studied 470 healthy white subjects, aged 44–50 years, participating in the Women's Healthy Lifestyle Project. Each participant was genotyped for theBsmI polymorphism at the VDR gene locus. BMD at the lumbar spine, hip and whole-body, and the whole-body soft tissue composition, were measured cross-sectionally using a Hologic QDR 2000 densitometer. The presence of a polymorphic restriction site at the VDR gene locus was specified asb, whereas absence of this site wasB. The frequency distribution of the VDR genotype was:bb, 20.6%;Bb, 39.1%; andBB, 40.2%. Spinal BMD (mean±SD) was significantly lower in women with VDR genotypeBB (1.038±0.11 g/cm2) as compared with those with genotypebb (1.069±0.12 g/cm2,p〈0.05). Trochanter BMD was 2.7% lower in those with genotypeBB versusbb (0.685±0.10 g/cm2 vs 0.708±0.09 g/cm2). A similar trend was shown at each subregion of the hip, but not at the whole-body. In premenopausal women, allelic status at the VDR locus contributed to variations in spinal and trochanteric BMDs, but the absolute difference in BMDs was small, amounting to 0.26 and 0.23 standard deviations, respectively. It is concluded that in this population of healthy premenopausal women there was a significant association between polymorphisms at the VDR gene locus and both spinal and trochanteric BMDs, yet no association was demonstrated for the whole-body BMD.
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  • 3
    ISSN: 1432-0428
    Keywords: Physical activity ; obesity ; fat distribution ; glucose intolerance ; Pima Indians ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationships between physical activity, obesity, fat distribution and glucose tolerance were examined in the Pima Indians who have the highest documented incidence of non-insulin-dependent diabetes. Fasting and 2-h post-load plasma glucose concentrations, body mass index, and waist-to-thigh circumference ratios were determined in 1054 subjects aged 15–59 years. Current (during the most recent calendar year) and historical (over a lifetime) leisure and occupational physical activity were determined by questionnaire. Current physical activity was inversely correlated with fasting and 2-h plasma glucose concentrations, body mass index and waist-to-thigh ratios for most sex-age groups even when diabetic subjects were excluded. Controlled for age, obesity and fat distribution, activity remained significantly associated with 2-h plasma glucose concentrations in males. In subjects aged 37–59 years, individuals with diabetes compared to those without reported significantly less leisure physical activity during the teenage years (median hours per week of activity, 9.1 vs 13.2 for men; 1.0 vs 2.2 for women). Controlled for body mass index, sex, age and waist-to-thigh ratio, subjects who reported low levels of historical leisure physical activity had a higher rate of diabetes than those who were more active. In conclusion, current physical activity was inversely related to glucose intolerance, obesity and central distribution of fat, particularly in males. Subjects with diabetes were currently less active and reported less historical physical activity than non-diabetic subjects. These findings suggest that activity may protect against the development of non-insulin-dependent diabetes both directly and through an influence on obesity and fat distribution.
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; aetiology ; HLA type ; virus ; islet cell ; autoantibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic, immunological and viral factors have been implicated in pathogenesis of Type 1 diabetes mellitus. The development of Type 1 diabetes in two siblings of patients with Type 1 diabetes studied as part of a large epidemiological study, is described. One case, a 13-year-old male not sharing either HLA haplotype with his diabetic sister, had virtually normal glucose tolerance 80 days before symptomatic presentation. He showed serological evidence of infection by Coxsackie CB4 (at diagnosis) and influenza A virus (soon after diagnosis). The other case, a 15-year-old male, had impaired glucose tolerance for over 500 days (i. e., since the diagnosis of diabetes in his HLA-identical brother) before symptomatic presentation which was not associated with serological evidence of acute viral infection. The former case was negative for islet cell antibody (cytoplasmic) when first seen though positive at diagnosis, while the latter was positive throughout. These two cases suggest contrasting interactions of the main pathogenetic factors associated with Type 1 diabetes.
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  • 5
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; Genetics ; Aetiology ; Glucose tolerance ; HLA type ; Islet cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this report, we present an analysis of glucose and insulin responses during oral glucose tolerance tests in 369 siblings of Type 1 diabetic patients. All have been HLA typed at the A, B and C loci. Though most had normal glucose tolerance by National Diabetes Data Group criteria (92% of the males and 95% of the females), siblings who shared both HLA haplotypes with the diabetic patient in the family had higher mean 3-hour glucose areas than those who shared one or neither HLA haplotype (p 〈 0.01). This difference was more marked in males and older siblings. Insulin concentrations did not differ significantly between the two groups except that, for those aged 〈16 years, the group sharing both haplotypes had lower fasting insulin concentrations (p = 0.05); for 16–29 year olds, the corresponding group had marginally higher 3-hour insulin areas than the remainder of siblings (p = 0.17). Little association with specific haplotypes (A1B8 or A2B15) was seen. Multivariate analyses, adjusting for age and obesity, eliminated the 3-h glucose difference in females by HLA sharing status (p = 0.37) although in males it remained significant (p 〈 0.001). Failure to account for age, sex and obesity may explain some of the conflicts in the reported literature. The glucose tolerance differences seen by HLA haplotype sharing status did not correlate with the presence of anti-islet cell antibodies. These results are consistent with the hypothesis that the HLA identical siblings, particularly males, have different (i. e. worse) glucose tolerance than their haplo-identical and non-HLA identical siblings.
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  • 6
    ISSN: 1432-0827
    Keywords: Key words: Genetics — Osteoporosis — Quantitative ultrasound — Alpha-2-HS glycoprotein — Polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in α2HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66–92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575+ and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P 〈 0.05) and 16% lower in homozygous AHSG*1 women (P 〈 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature.
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  • 7
    ISSN: 1432-0827
    Keywords: Key words: Cytokines — Bone mineral density — Premenopausal — Interleukin-1 — Interleukin-6 — Tumor necrosis factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss were observed in women with ``high'' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high'' =−1.56% ± 0.70 versus ``low'' (〈75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites.
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  • 8
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total community (Allegheny County, Pennsylvania) Type 1 (insulin-dependent) diabetes mellitus registry was examined for evidence of seasonality at onset of the disease. No significant seasonal trend was found if all cases aged 〈 20 years at onset (n = 901) were considered. However, a significant pattern emerged for the age groups 5–9 years and 10–14 years. Furthermore, sex differences were apparent in that males but not females demonstrated a seasonal pattern (fewer cases in the summer months).
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  • 9
    ISSN: 1432-0428
    Keywords: Type I diabetes mellitus (juvenile) ; birth order ; maternal age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of patients having onset of Type I (insulin-dependent) diabetes mellitus before age 17 years was identified from consecutive admissions to the Children's Hospital of Pittsburgh. Family history data were obtained yielding 1006 families (1085 cases) with complete information. The prevalence of diabetes among the children differed by birth order, with a greater number than expected among first born. There was also an increased prevalence among children born to mothers older than 35 years, as well as an increased prevalence among children of very young mothers. The increased prevalence of diabetes among offspring of older mothers was apparent even after life table age corrections were made. However, both the increased prevalence among first born children and the increased prevalence among children of very young mothers could be attributed to an older attained age of these children in this particular population. This indicated that the maternal age effect was present but a birth order effect was absent when age was taken into account.
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  • 10
    ISSN: 1433-2965
    Keywords: Bone quality ; Broadband ultrasound attenuation ; Epidemiology ; Osteoporosis ; Quantitative ultrasound ; Speed of sound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.
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