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- Carlzon, Daniel, et al.
(författare)
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Both Low and High Serum Insulin-like Growth Factor-I Levels Associate with Increased Risk of Cardiovascular Events in Elderly Men.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:11
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Most previous prospective studies suggest that low serum insulin-like growth factor-I (IGF-I) associates with increased risk of cardiovascular disease (CVD) events while other studies suggest that high serum IGF-I associates with increased risk of CVD events. We tested the hypothesis that not only low, but also high, serum IGF-I associate with increased risk of CVD events in elderly men. Methods and Results: Serum IGF-I levels were measured in 2901 elderly men (aged 69 to 81 years) included in the prospective population-based MrOS-Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of follow-up. During follow-up (median 5.1 yrs) 589 of the participants experienced a CVD event. The association between serum IGF-I and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CVD events (p<0.01 for nonlinearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio (HR) = 1.25, 95% confidence interval (CI) 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-I associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusion: Both low and high serum IGF-I levels are risk markers for CVD events in elderly men. The association between high serum IGF-I and CVD events is mainly driven by CHD events.
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| 3. |
- Mellström, Dan, 1945, et al.
(författare)
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Older men with low serum estradiol and high serum SHBG have an increased risk of fractures.
- 2008
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Ingår i: Journal of bone and mineral research. - 1523-4681. ; 23:10, s. 1552-60
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.
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| 4. |
- Swanson, Charlotte, 1975, et al.
(författare)
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The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men.
- 2007
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Ingår i: Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4878-82
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: To determine in vivo if the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n=1068, age=18.9 years) and elderly (n=1001, age=75.3 years) men. Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) measured by GC-MS and serum levels of the major glucuronidated androgen metabolites androstane-3alpha,17beta-diol(androstanediol)-3glucuronide, androstanediol-17glucuronide and androsterone-glucuronide measured by LC-MS/MS. Body composition measured by DXA. Results: Both the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17glucuronide (p<0.001) but not with levels of androstanediol-3glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D(85)Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (p<0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (p<0.05) as indicated by the HOMA index. Conclusions: The UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17 glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17 glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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