The association between serum testosterone and insulin resistance: a longitudinal study

The objective of this study was to investigate whether there is a bidirectional association between testosterone concentrations and insulin resistance, in a prospective population study. A random population sample of 1400 men, aged 30–74, was examined in 2002–2005 in southwestern Sweden and followed up in 2012–2014 (N = 657). After excluding subjects without information on sex hormones and insulin resistance, 1282 men were included in the baseline study. Fasting measurements of plasma glucose, insulin and hormones were performed. Insulin resistance was defined using HOMA-Ir. Mean age at baseline was 47.3 ± 11.4 years. From the follow-up survey 546 men were included, mean age 57.7 ± 11.6 years. Low concentrations of total testosterone at baseline were significantly associated with high logHOMA-Ir at follow-up in a multivariable model including age, waist–hip ratio, physical activity, alcohol intake, smoking, LDL, CRP, hypertension, diabetes and logHOMA-Ir at baseline as covariates (β = −0.096, P = 0.006). Similar results were observed for bioavailable testosterone. Men within the lowest quartile of total testosterone at baseline had significantly higher logHOMA-Ir at follow-up than other quartiles (Q1 vs Q2 P = 0.008, Q1 vs Q3 P = 0.001, Q1 vs Q4 P = 0.052). Multivariable analysis of the impact of insulin resistance at baseline on testosterone levels at follow-up revealed no significant associations regarding testosterone concentrations (β = −0.003, P = 0.928) or bioavailable testosterone (β = −0.006, P = 0.873), when adjusting for baseline concentrations of total testosterone, age, waist–hip-ratio, LDL, CRP, physical activity, alcohol intake, smoking, hypertension and diabetes. Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up

Sex hormones and cardiovascular risk in men and women. The Skaraborg Project

The general aim of this thesis was to explore the associations between sex hormones and high blood pressure in men and women and to investigate their further role in the development of acute myocardial infarction particularly with regard to the large effect of type 2 diabetes, especially seen in women. Differences in levels of sex hormones and their specific effects in men and women might partially explain the differences in cardiovascular risk between men and women. Our specific aims were to investigate the relationship between sex hormones and high blood pressure as a major risk factor for cardiovascular disease, to investigate mechanisms that control the concentrations of sex hormone-binding globulin (SHBG), to investigate testosterone as a risk factor for AMI in men and women, to explore the modifying effect of type 2 diabetes on the outcome, and to investigate the association between sex hormones and cardiovascular disease, stroke and AMI, in men and women with or without type 2 diabetes. This thesis included studies on 2 cohorts:1. A population survey in the municipalities of Vara and Skövde (VSC) 2002-2005 (n=2816, aged 30-74 years, 50% female, participation rate 76%); 2. A population survey in the municipality of Skara (SC3) 1993-1994 (n=1109, aged 40-80+ years, 50% female, participation rate 79%). Findings: Low concentrations of SHBG were associated with high blood pressure in men, whereas SHBG was independently associated with hypertension in postmenopausal women. We also found that insulin levels were independently associated with SHBG levels. Low testosterone levels in men with diabetes significantly predicted AMI independently of major cardiovascular risk factors. Endogenous estradiol concentrations were significantly associated with stroke risk in both sexes but with opposite relationships; estradiol was associated with reduced stroke risk in women, but with increased stroke risk in men. In conclusion, concentrations of sex hormones predicted cardiovascular morbidity in both men and women, albeit differently. While testosterone was protective in men, estradiol and SHBG were protective in women. Moreover, SHBG seems to play an active role in the modulation of sex hormone effects, as it was found to be independently associated with hypertension. However, more studies are needed to explore the association of this globulin with diabetes and hypertension, in order to confirm our results suggesting a role of insulin in the control of SHBG. Correspondingly, the effects of estradiol in men seem negative while the effects of testosterone in women were uncertain. Thus, in each sex the characteristic hormone supports health. Diabetes also modified the association between concentrations of sex hormones and CVD in both sexes. These modifications might at least partially explain the loss of cardiovascular protection in women when they develop type 2 diabetes

HbA1c räcker inte vid screening för störd glukosmetabolism - Även glukosbelastning behövs, visar svensk prospektiv epidemiologisk studie.

An HbA1c threshold of ≥42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended

Epidemiological and clinical implications of blood pressure measured in seated versus supine position

The evidence concerning how posture influences blood pressure is not consistent. The aim of this cross-sectional study was to consider the clinical and epidemiological implications of blood pressure measured in seated versus supine position, and to investigate the impact of age, sex, body mass index (BMI), and diabetes on these differences.This study included 1298 individuals (mean age 58.6 ± 11.8 years) from the Vara-Skövde cohort at the 10 years' follow-up visit in 2014. Physical examination included blood pressure measurements in seated and supine position. Self-reported information on diabetes status, hypertension, ongoing medication, leisure time physical activity, and smoking habits were obtained. Linear regression models accounted for differences in age, sex, BMI, and known diabetes.Both systolic and diastolic blood pressure were significantly higher in the seated position [1.2 mm Hg, P < .001, 95% confidence interval (95% CI) 0.79-1.54 and 4.2 mm Hg, P < .001, 95% CI 4.08-4.71, respectively]. The prevalence of high blood pressure in seated position was higher (19.9%) than in supine position (13.5%). Linear regression analysis showed that age (β = -0.215, P < .001) and diabetes (β = -0.072, P = .012) were associated with smaller differences in postural diastolic blood pressure and BMI (β = 0.124, P < .001) with greater difference.This study showed substantial postural differences in blood pressures measured in office. Measuring blood pressure in the supine position shows lower blood pressure readings when compared with the seated position. Clinicians should be aware of how age, BMI, and diabetes influence these differences

Longitudinal association between leisure-time physical activity and vascular elasticity indices.

AimWe investigated the association between levels of leisure-time physical activity and vascular stiffness in a longitudinal observational study from a representative Swedish population.MethodA total of 2816 randomly selected individuals were examined at visit 1 (2002-2005, Men = 1400). After a mean follow-up of 9.7 ± 1.4&nbsp;years, a representative sample of 1327 of the original participants were re-examined at visit 2. After excluding subjects with hypertension at baseline, 761 participants were included in the longitudinal analyses. Leisure-time physical (LTPA) activity was self-reported and dichotomized as high or low (level 3, 4 and level 1, 2, respectively). Large Arterial Elasticity Index (LAEI) and Small Arterial Elasticity Index (SAEI) were measured using the HDI/Pulse Wave™ CR2000. Multivariable general linear models were used to investigate the differences in changes SAEI and LAEI based on LTPA levels.ResultsAt visit 1, and after adjustment for possible confounders, participants in the high LTPA group had better small artery elasticity (SAEI) (SAEI in low-level LTPA: 7.89 ± 0.11, SAEI in high-level LTPA: 8.32 ± 0.15, ΔSAEI: 0.42, CI: 0.07-0.78; p = 0.020). SAEI decreased between the two assessments (Visit 1: SAEI 8.01 ± 3.37&nbsp;ml/mmHg; Δ SAEI: 1.4, CI 1.2-1.6, p &lt; 0.001). Participants with a higher LTPA at visit 1 had significantly better SAEI at visit 2 (ΔSAEI: 0.44, CI 0.03-0.85, p = 0.037). No significant associations were observed between LAEI and LTPA after adjustments.ConclusionsHigh LTPA predicted higher small arterial compliance at visit 2 suggesting that positive effects of LTPA on arterial elasticity persists over time

Clusters of AMI risk factors and their association with left ventricular hypertrophy: A population-based study within the Skaraborg Project, Sweden.

Risk factors for acute myocardial infarction (AMI) are known to cluster and to be differently distributed in men and women. The aim of this study was to sex-specifically explore clusters of acknowledged AMI risk factors by factor analysis, and to study whether such clusters are associated with left ventricular hypertrophy (LVH), used as a subclinical measure of CHD

Longitudinal association between leisure-time physical activity and vascular elasticity indices

Aim: We investigated the association between levels of leisure-time physical activity and vascular stiffness in a longitudinal observational study from a representative Swedish population. Method: A total of 2816 randomly selected individuals were examined at visit 1 (2002–2005, Men = 1400). After a mean follow-up of 9.7 ± 1.4 years, a representative sample of 1327 of the original participants were re-examined at visit 2. After excluding subjects with hypertension at baseline, 761 participants were included in the longitudinal analyses. Leisure-time physical (LTPA) activity was self-reported and dichotomized as high or low (level 3, 4 and level 1, 2, respectively). Large Arterial Elasticity Index (LAEI) and Small Arterial Elasticity Index (SAEI) were measured using the HDI/Pulse Wave™ CR2000. Multivariable general linear models were used to investigate the differences in changes SAEI and LAEI based on LTPA levels. Results: At visit 1, and after adjustment for possible confounders, participants in the high LTPA group had better small artery elasticity (SAEI) (SAEI in low-level LTPA: 7.89 ± 0.11, SAEI in high-level LTPA: 8.32 ± 0.15, ΔSAEI: 0.42, CI: 0.07–0.78; p = 0.020). SAEI decreased between the two assessments (Visit 1: SAEI 8.01 ± 3.37 ml/mmHg; Δ SAEI: 1.4, CI 1.2–1.6, p < 0.001). Participants with a higher LTPA at visit 1 had significantly better SAEI at visit 2 (ΔSAEI: 0.44, CI 0.03–0.85, p = 0.037). No significant associations were observed between LAEI and LTPA after adjustments. Conclusions: High LTPA predicted higher small arterial compliance at visit 2 suggesting that positive effects of LTPA on arterial elasticity persists over time

Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population

Background: The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population. Methods: The study is based on a random sample of a Swedish population of men and women aged 30-74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 x (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7. Results: In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: beta=-0.143 p<0.001) and systolic blood pressure (systolic blood pressure beta=-0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: beta=-0.113 p<0.001; systolic blood pressure beta=-0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=-0.024 p<0.001) and women (B=-0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=-0.014, p=0.008). Conclusion: In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure