Bone mineral density and bone turnover in relation to serum leptin, α-ketoglutarate and sex steroids in overweight and obese postmenopausal women

Objective Recent studies have shown that parallel changes in body weight and bone mass can be partially mediated via circulating leptin. Therefore, among the hormones involved in bone and mineral metabolism, such as oestrogens, testosterone and parathormone, leptin has recently become a subject of considerable interest. The aim of this study was to assess associations between leptin, E₂, testosterone, dehydroepiandrosterone sulphate (DHEA‐S), SHBG, α‐ketoglutaric acid (AKG) and bone mineral density (BMD) and bone turnover markers in overweight and obese postmenopausal women. Design Eighty healthy, postmenopausal Caucasian women were studied. BMD of the lumbar spine (L₂–L₄) and femoral neck regions were examined using the dual X‐ray absorptiometry (DXA) method. Associations were evaluated in stepwise multiple regression analysis, including information on the possible confounders and effect modifiers, for example, age, years since menopause, height and weight. Results Femoral neck BMD was positively correlated with weight (r = 0·52, P < 0·000001), body mass index (BMI) (r = 0·48, P < 0·000006), hipline (r = 0·48, P < 0·00006), waistline (r = 0·45, P < 0·00002) and DHEA‐S (r = 0·36, P < 0·0008). Correlations of E₂, SHBG, testosterone and leptin, as well as biochemical markers of bone turnover with L₂–L₄ and femoral neck BMD were not found. In the whole study group, significant predictors of L₂–L₄ BMD were BMI (β = 0·35, P < 0·01) testosterone (β = 0·27, P < 0·05) and osteocalcin (OC) (β = 0·22, P < 0·05) (R² = 0·23), while predictors of femoral neck BMD were BMI (β = 0·42, P < 0·001), testosterone (β = 0·24, P < 0·05), E₂ (β = 0·19, P < 0·05), as well as osteocalcin (β = 0·20, P < 0·05) (R² = 0·41). In the subgroup with BMI 30–39·9, the significant predictors of both L₂–L₄ and femoral neck BMD were testosterone (β = 0·32, P < 0·05, R² = 0·19; β = 0·33, P < 0·05, R² = 0·29) and osteocalcin (β = 0·34, P < 0·05, R² = 0·19; β = 0·45, P < 0·01, R² = 0·29). In the subgroup with waist : hip ratio (WHR ≥ 0·85, the predictor of L₂–L₄ BMD was E₂ (β = 0·38, P < 0·05) (R² = 0·21), whereas the predictors of femoral neck BMD were BMI (β = 0·29, P < 0·05) and testosterone (β = 0·35, P < 0·01) (R² = 0·36). Conclusion The main endocrine variable predicting lumbar spine BMD in overweight and obese postmenopausal females was testosterone, while the main determinants of femoral neck BMD were both testosterone and E₂. No effect was found of serum leptin on examined indicators of bone status.     

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease

Background and Objective High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. Patients and Measurements We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54·4 ± 1·8 years) or HD (n = 38, 22 males and 16 females, age 60·8 ± 1·6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. Results PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28·7 (13·0–71·9) µg/l] than those found in patients on HD [9·7 (4·7–31·9) µg/l, P < 0·01] or in conservative management [5·9 (4·3–38·6) µg/l, P < 0·05]. Adiponectin concentrations were similar in the three groups of patients (mean ± SEM, 48·0 ± 4·5 mg/l in PD, 57·7 ± 4·4 mg/l in HD, and 44·4 ± 7·0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26·3 ± 0·99 and 27·5 ± 1·4 µg/l, respectively, vs. 17·3 ± 1·0 µg/l, P < 0·001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0·287, P < 0·01) and adiponectin levels were negatively related to BMI (r = ?0·416, P < 0·001) and the homeostatic model assessment (HOMA‐R) index (r =?0·216, P < 0·05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1·80 (1·03–3·15), P = 0·039] was found when analysing subgroups of patients. Conclusions These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.     

Leptin—a parameter for body fat measurement in patients with eating disorders

Plasma levels of leptin correlate with the body mass index and even more with percentage body fat. Determinations of leptin levels might thus offer an alternative to easily assess fat mass in patients with eating disorders. Twenty-five females with the DSM-IV diagnosis of anorexia nervosa (n=12, mean BMI 13·8) and bulimia nervosa (n=13, mean BMI 21·7), respectively, were examined upon referral for inpatient treatment. Methods for the measurement of body fat were BMI and plasma leptin level; dual-energy X-ray absorptiometry (DXA) was used as a reference method. Leptin levels showed a highly significant correlation to body fat measured by DXA (r=0·95, p<0·001). In the group of anorexia patients the correlation of leptin levels with DXA (r=0·91, p<0·001) was significantly higher than with BMI (r=0·62, p<0·05). Measurement of leptin levels in AN patients is a promising approach for determining percentage body fat, especially at admission for inpatient treatment, prior to refeeding. © 1998 John Wiley & Sons, Ltd and Eating Disorders Association.     

Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism

Background Primary hyperparathyroidism (PHPT) is associated with reduced bone mineral density (BMD) mainly at sites rich in cortical bone. However, successful parathyroidectomy causes an increase in BMD especially at sites rich in trabecular bone. Plasma 25‐hydroxyvitamin D (25OHD) levels are typically reduced and plasma 1,25‐dihydroxyvitamin D [1,25(OH)₂D] slightly increased in PHPT. These variations in vitamin D metabolites may influence variations in BMD and fracture risk. Aim To investigate relations between preoperative vitamin D metabolites and skeletal consequences in patients with untreated PHPT and to appraise the influence of preoperative vitamin D metabolites on postoperative changes in BMD. Design Cross‐sectional and cohort study. Materials Two hundred and forty‐six consecutive Caucasian PHPT patients aged 19–91 years. (median 63, 87% females). Results BMD was reduced at the femoral neck (P < 0·001) and forearm (P < 0·001), but normal at the lumbar spine (P = 0·11). Levels of biochemical bone markers were associated with high plasma PTH, high plasma 1,25(OH)₂D and low plasma levels of 25OHD. Moreover, low plasma 25OHD was associated with low levels of BMD at the femoral neck (r_p = 0·23), the forearm (r_p = 0·19) and the whole body (r_p = 0·30), whereas plasma 1,25(OH)₂D was inversely associated with BMD at all regional sites and the whole body. Plasma PTH only showed an inverse association with BMD at the forearm (r_p = –0·21). No association was observed between biochemical variables and prevalent spinal fractures, all peripheral fractures or osteoporotic peripheral fractures. The annual increase in spinal BMD after surgery was positively associated with preoperative plasma PTH (r_p = 0·40), whereas the annual increase in whole body BMD was inversely associated with plasma 25OHD (r_p = –0·32). No change in BMD at the femoral neck and forearm was observed 1 year after surgery. Conclusion Low vitamin D status and high plasma 1,25(OH)₂D are associated with increased bone turnover and decreased BMD in patients with PHPT.     

High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus

Objectives In type 2 diabetes mellitus, circulating C‐reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)‐associated, anti‐oxidative and anti‐inflammatory enzyme, paraoxonase‐I, is decreased. Both high CRP and low paraoxonase‐I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase‐I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase‐I when taking account of plasma levels of pro‐ and anti‐inflammatory adipokines. Design and patients In 81 type 2 diabetic patients and 89 control subjects, plasma high‐sensitive CRP, serum paraoxonase‐I activity (arylesterase activity, assayed as the rate of hydrolysis of phenyl acetate into phenol), plasma leptin, adiponectin, resistin and lipids were determined. Results Body mass index (BMI), waist, insulin resistance, triglycerides, CRP, leptin and resistin levels were higher (P < 0·05 to P < 0·001), whereas HDL cholesterol, paraoxonase‐I activity and adiponectin levels were lower (P = 0·02 to P < 0·001) in diabetic compared to control subjects. Multiple linear regression analysis demonstrated that, after controlling for age and gender, CRP was inversely related to paraoxonase‐I activity (β = –0·15, P = 0·028) and adiponectin (β = –0·18, P = 0·009), and positively to leptin (β = 0·33, P < 0·001) and BMI (β = 0·22, P = 0·007), independently of the diabetic state (or of fasting glucose or HbA1c), insulin resistance and lipids (P > 0·20 for all). Conclusions low paraoxonase‐I activity is related to higher CRP, independently of adipokines, as well as of obesity and lipids. Low paraoxonase‐I activity in type 2 diabetes mellitus may contribute to increased cardiovascular risk via an effect on enhanced systemic low‐grade inflammation.     

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism

Objective The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH). Methods Forty‐one patients with SH, as judged by elevated serum TSH levels and free thyroid hormones within the normal range, and 31 sex‐ and age‐matched euthyroid volunteers underwent two‐dimensional conventional ultrasonography and IBS analysis of the carotid wall. Carotid intima–media thickness (IMT) and corrected IBS (C‐IBS), an index of arterial wall degeneration and fibrosis, were evaluated. Results Mean IMT as well C‐IBS values were higher in SH than in controls (P < 0·0001 for both), whereas the carotid diameter was not significantly different between the two groups. The distribution of C‐IBS values in each group showed that regions with higher C‐IBS values were found more frequently in SH patients than in control subjects. The percentage of regions that could be considered as fibromatous (C‐IBS value from –18 to –21 dB) was 28% in SH and 9% in euthyroid subjects (P < 0·0001). In the SH group, C‐IBS values were significantly and positively associated with plasma TSH (r = 0·32, P < 0·05 and r = 0·59, P < 0·0001, respectively) and with both total cholesterol (r = 0·46, P = 0·01) and low density lipoprotein (LDL)‐cholesterol (r = 0·55, P = 0·001). Conclusions Carotid IMT in subclinically hypothyroid patients is higher than that in euthyroid controls. This is characterized by increased IBS values, which are related to the collagen content of the arterial wall. The severity of this remodelling process seems to be related to TSH and cholesterol levels.     

Relationships between vascular resistance and energy deficiency, nutritional status and oxidative stress in oestrogen deficient physically active women

Objective Oestrogen deficiency contributes to altered cardiovascular function in premenopausal amenorrheic physically active women. We investigated whether other energy deficiency‐associated factors might also be associated with altered cardiovascular function in these women. Design A prospective observational study was completed at a research facility at the University of Toronto. Participants Thirty‐two healthy premenopausal women (18–35 years old) were studied; 9 sedentary and ovulatory; 14 physically active and ovulatory; and 8 physically active and amenorrheic. Measurements We measured calf vascular resistance, resting heart rate, dietary energy intake, resting energy expenditure and serum measures of homocysteine, high‐sensitivity C‐reactive protein, oxidized low‐density lipoproteins, total T₃, ghrelin, leptin and insulin. Results Groups were similar (P > 0·05) in age (25·1 ± 0·8 years; mean ± SEM), weight (57·3 ± 1·1 kg), and BMI (21·4 ± 0·3 kg/m²). Resting vascular resistance and ghrelin were highest (P < 0·05, main effect), and total T₃ and energy expenditure adjusted for fat free mass lowest (P < 0·05, main effect) in oestrogen deficient women. Using pooled data for stepwise multiple regression modelling: ghrelin and resting energy expenditure adjusted for fat free mass were associated with resting vascular resistance (R² = 0·398, P = 0·018); adjusted dietary energy intake was associated with peak‐ischaemic vascular resistance (R² = 0·231, P = 0·015). Adjusted resting energy expenditure (r = 0·624, P < 0·001) and total T₃ correlated (r = 0·427, P = 0·019) with resting heart rate. Homocysteine, high‐sensitivity C‐reactive protein and oxidized low‐density lipoproteins were similar (P > 0·05, main effect) among the groups, and were unrelated to cardiovascular measures. Conclusion Altered resting vascular resistance in premenopausal oestrogen deficient physically active amenorrheic women is not associated with vascular inflammation or oxidative stress, but rather with parameters that reflect metabolic allostasis and dietary intake, suggesting a potential role for chronic energy deficiency in vascular regulation.     

Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study

Objectives Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids. Design Cross‐sectional Subjects and measurements We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12–18 years old. Fasting blood was drawn for active ghrelin, leptin, E₂ and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI). Results AA girls had lower BMI than EA and controls (P = 0·003). Log ghrelin was higher in AA than in EA and controls (P < 0·0001), and remained higher after controlling for BMI Z‐scores. Leptin was lower in AA than in the other groups (P < 0·0001), however, the differences did not persist after controlling for BMI Z‐scores. Testosterone was lower in AA than in EA and controls (P = 0·002) and log E₂ trended lower in AA (P = 0·07). We observed inverse associations of log active ghrelin with testosterone (P = 0·01), and positive associations of leptin with testosterone and log E₂ (P = 0·02 and 0·009). Conclusion Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes.     

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes

Objective The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline. Design The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80·0%) participated in the 5‐year follow‐up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B‐mode ultrasonography of the thyroid was performed. Results In the reference population, there was a urinary iodine‐related increment of serum TSH levels (r = 0·21, P = 0·000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1·15, 1·28 and 1·93 mIU/l, respectively (P = 0·000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0·3–4·8 mIU/l. TSH concentrations obtained in the follow‐up study correlated well with those at baseline (r = 0·58, P = 0·000). A baseline serum TSH > 1·9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1·0 mIU/l was associated with an increased incidence of subnormal TSH development. Conclusions Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1·0–1·9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.     

Enhanced proatherogenic inflammation after recombinant human TSH administration in patients monitored for thyroid cancer remnant

Objective To evaluate the effect of recombinant human TSH (rhTSH) on biomarkers of vascular endothelial cell and platelet activation in patients monitored for thyroid carcinoma remnant. Methods Circulating levels of soluble(s) intercellular adhesion molecule (sICAM)‐1 and sE‐selectin, as indices of vascular endothelial cell activation, of sP‐selectin and sCD40 ligand (sCD40L), as indices of platelet activation, and of 8‐iso‐prostaglandin F_2α (8‐iso‐PGF_2α), as an index of lipid peroxidation, were evaluated in 20 patients (16 females, 48·0 ± 13·6 years) at baseline and after intramuscular rhTSH injection (0·9 mg/day on two consecutive days). Results At baseline, serum TSH values were below normal whereas free T3 and free T4 were within the normal range. After rhTSH injection, serum TSH increased significantly but free T3 and free T4 remained unchanged. Concomitantly, plasma sICAM‐1 concentrations increased significantly (from 155·9 ± 39·1 to 183·6 ± 38·1 ng/ml, P < 0·03), as did those of sE‐selectin (from 74·8 ± 15·4 to 91·4 ± 12·2 ng/ml, P < 0·0006), sP‐selectin (from 56·4 ± 13·7 to 72·2 ± 14·9 ng/ml, P < 0·002), sCD40L (from 2·1 ± 0·9 to 2·8 ± 1·1 ng/ml, P < 0·03) and total 8‐iso‐PGF_2α(from 238·5 ± 47·0 to 307·8 ± 41·2 pg/l, P < 0·0001). Changes in circulating levels of sCD40L were directly correlated with changes in levels of plasma total 8‐iso‐PGF_2α (r = 0·523, P < 0·02) and sP‐selectin (r = 0·480, P < 0·03). Conclusions Supraphysiological concentrations of rhTSH might exert proatherogenic effects by promoting activation of vascular endothelial cells and platelets probably through enhanced oxidative stress.     

Significant inverse relationship between serum free T4 concentration and body mass index in euthyroid subjects: differences between smokers and nonsmokers

Objective There are conflicting data regarding the relationship between thyroid function and body mass index (BMI) in euthyroid subjects, and it is uncertain whether tobacco smoking modifies this relationship. The objective of this study was to examine the relationships between thyroid function, BMI and smoking in euthyroid subjects. Design Linear regression models were used to examine the relationships between serum free T4, serum TSH, BMI and smoking in a cross‐sectional, community‐based sample of 1853 euthyroid subjects in Busselton, Western Australia. Results There was a significant negative relationship between free T4 and BMI: after adjustment for age and sex, each 1 pmol/l increase in free T4 was associated with a decrease in BMI of 0·12 kg/m² (95% CI 0·06, 0·18; P < 0·001). The mean BMI ± SD of subjects in the highest quintile of free T4 concentration was 24·4 ± 3·5 kg/m², compared with 26·1 ± 3·8 kg/m² for the lowest quintile. The relationship between free T4 and BMI was statistically significant (adjusted for age and sex) in subjects who had never smoked (P = 0·001) and former smokers (P = 0·011), but not in current smokers (P = 0·77). There was no significant relationship between TSH and BMI: after adjustment for age and sex, each 1 mU/l increase in TSH was associated with an increase in BMI of 0·08 kg/m² (95% CI –0·16, 0·32; P = 0·53). Conclusions In euthyroid subjects, small differences in free T4 are associated with differences in BMI. This relationship is not present in current smokers. We speculate that this may be relevant to weight changes associated with smoking cessation.     

Serum testosterone and bioavailable testosterone correlate with age and body size in hypogonadal men treated with testosterone undecanoate (1000 mg IM--Nebido)

Objective To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido®) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied. Design Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy. Patients 51 hypogonadal men (35, 68·6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy. Measurements Patients received an IM injection of Nebido (1000 mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA). Results Baseline TT (mean 11·5 nmol/l, range 0·3–54·8) increased by 50% after commencing Nebido (17·2 nmol/l (5·4–32·8), P = 0·0001). 75% of subjects had a TT within the reference range (8·0–25·0 nmol/l). Subjects with primary hypogonadism had a higher 18‐week TT [20·9 nmol/l (9·8–32·8) vs. 15·5 (5·4–32·6), P = 0·02] and SHBG [39·2 nmol/l (11–82) vs. 25·7 (9·0–60·0), P = 0·003] although the cBioT was not significantly different [4·9 nmol/l (2·9–7·3) vs. 4·2 (2·0–7·9), P = 0·12]. The 18‐week TT positively correlated with age (R = 0·36, P = 0·01) and negatively correlated with weight (R = –0·38, P = 0·006), BMI (R = –0·42, P = 0·002) and BSA (R =–0·38, P = 0·007). Similarly cBioT correlated with age (R = 0·28, P = 0·04), weight (R = –0·29, P = 0·03), BMI (R = –0·30, P = 0·03) and BSA (R = –0·27, P = 0·05). Age (t = 2·04, P = 0·05) and baseline testosterone (t = –9·26, P < 0·0001) were independent variables of the increase in TT at 18 weeks. Conclusion This starting regimen is simple and provides the majority of men with a TT within the reference range. Age and baseline TT are independent variables of the increase in TT with IM testosterone undecanoate. At week 18 age and body size correlated with the cBioT and TT and this may then be used to estimate dosing frequency for this therapy.     

Inflammatory markers and visceral fat are inversely associated with maximal oxygen consumption in women with polycystic ovary syndrome (PCOS)

Background We investigated whether several different inflammatory markers including C‐reactive protein (CRP) and fibrinogen and white blood cells (WBCs) count, are associated with maximal oxygen consumption (VO_2max) in women with polycystic ovary syndrome (PCOS). Methods In PCOS women (n = 124, 24·1 ± 4·5 year‐old) VO_2max was measured during symptom‐limited cardiopulmonary exercise test. Abdominal fat distribution was determined by ultrasound. Physical activity level was assessed by a standardized questionnaire. CRP was measured by immunoassays, fibrinogen by the Clauss method, and WBCs count with a Coulter counter. Results Pearson's analysis showed a significant correlation between VO_2max and logCRP (r = –0·437, P < 0·001), fibrinogen (r = –0·479, P < 0·001), and WBCs count (r = –0·438, P < 0·001). Multivariable logistic regression model showed that age (β = –0·127, P = 0·005), AUC_INS (β = –0·335, P < 0·001), HDL‐C (β = 0·390, P < 0·001), physical activity score (β = 0·238, P = 0·002), visceral fat (β =–0·184), P = 0·023), FAI (β = –0·291, P = 0·028); CRP (β = –0·216, P = 0·011), fibrinogen (β = –0·113, P = 0·008) and WBCs count (β = –0·177, P < 0·001) were significantly associated with VO_2max. Conclusions Acute‐phase reactants, such as CRP and fibrinogen, and WBCs count were independently and inversely associated with a direct measure of cardiorespiratory fitness (VO_2max) in women with PCOS, even after adjustment for physical activity level and other potential confounding factors. These findings add to the growing body of evidence linking inflammation to cardiorespiratory fitness in PCOS women.     

Human RBP4 adipose tissue expression is gender specific and influenced by leptin

Objective The role of retinol‐binding protein‐4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender‐specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender‐specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4. Research Design and Methods The study is an ex ‐ vivo prospective analysis of paired AT‐samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m², women: 38·4 ± 11kg/m²) and homeostasis model assessment of insulin resistance taken during elective surgery and ex‐vivo culture using visceral‐AT (VAT)‐explants (n = 10). Plasma RBP4 and cytokines were measured by ELISA and mRNA expression in AT by real‐time PCR. VAT‐explants were cultured with recombinant leptin and insulin and RBP4 determined by western blot analyses. Results Overall subcutaneous AT (SCAT)‐RBP4 mRNA expression was higher than VAT‐expression [3·1 ± 0·26 signal units (SU; mean ± SE) vs 1·79 ± 0·18 SU, n = 48, P < 0·0001], but neither correlated with circulating RBP4. SCAT‐RBP4 expression was higher in women and correlated with BMI (r = ?0·5, P = 0·009) and fat mass (r = ?0·5, P = 0·002). VAT‐RBP4 correlated positively with GLUT‐4 expression and adiponectin in men only (r = 0·54, P = 0·03 and r = 0·64, P < 0·002, respectively) when correcting for age and fat mass. Multiple regression determined leptin AT‐expression as a positive predictor of AT‐RBP4 in women (SCAT: β = 0·50, P = 0·002; VAT: β = 0·58, P = 0·003) and adiponectin for VAT‐RBP4 in men (β = 0·69; P = 0·001). AT‐RBP4 mRNA expression showed no relation with insulin resistance. Leptin stimulated RBP‐4 secretion ex‐vivo, whilst insulin did not affect RBP4. Conclusion AT‐derived RBP4‐mRNA expression is gender specific and regulated by leptin. Circulating RBP4 levels appear to be independent of AT‐RBP4 secretion.     

A paradoxical difference in relationship between anxiety, depression and thyroid function in subjects on and not on T4: findings from the HUNT study

Objective There have been conflicting reports on the relationship between thyroid function and mood between studies in subjects on T4 and the general population not on T4. We investigated this relationship in a large catchment area‐based study. Design We analysed data on serum TSH levels and Hospital Anxiety and Depression Scale (HADS) scores from the HUNT 2 study (age ≥ 40 years). Following a test for interaction, analyses were performed separately in females on T4 (n = 1265) and in people not on T4 (males n = 9319 and females n = 17 694). Results More females on T4 had high depression and anxiety scores than females not on T4 (depression 18·4%vs. 13·0%, P < 0·001, anxiety 23·4%vs. 18·7%, P < 0·001). In those not on T4, there was an inverse association between serum TSH and depression score in males (B coefficient = –0·61, 95% CI –0·91 to –0·24, P = 0·001) though not in females (B coefficient = –0·07, –0·33 to 0·19), and an inverse association between TSH and anxiety score in both genders (B coefficient for males = 0·68, 95% CI –1·04 to –0·32, P < 0·001; females –0·37, 95% CI –0·67 to –0·08, P = 0·01). In contrast, in females on T4, TSH was positively associated with both depression (B coefficient = +0·27, 95% CI 0·02 to 0·51, P < 0·05) and anxiety (B coefficient = +0·29, 95% CI 0·01 to 0·56, P < 0·05). Conclusions There is a different relationship between thyroid function and depression and anxiety in females on T4 compared with individuals with no thyroid disease. This group also has a higher prevalence of depression and anxiety.     

Adiponectin is an indicator of insulin resistance in non-obese prepubertal children born large for gestational age (LGA) and is affected by birth weight

Background and objective Being born as large for gestational age (LGA) has an increased risk of developing insulin resistance. Hypoadiponectinaemia is associated with insulin resistance. The aim of this study was to evaluate adiponectin levels and insulin resistance in association with body composition in LGA born non‐obese children at prepubertal ages. Patients and methods Thirty‐five (17 female and 18 male) LGA born non‐obese children (mean age 4·8 ± 0·3 years) were evaluated with respect to glucose, insulin, IGFBP‐1, leptin, adiponectin levels and body composition by DEXA. Their data were compared to that of non‐obese 49 (20 female, 29 male) appropriate for gestational age (AGA) children (mean age 3·8 ± 0·1 year). Results LGA children, who had similar body mass index standard deviation scores (BMI SDS) as AGA children, had significantly higher insulin (P = 0·043) and statistically borderline significant homeostasis model assessment‐insulin resistance (HOMA‐IR) levels (P = 0·054) than those of AGA children. Adiponectin levels were significantly lower in LGA than AGA children (P = 0·004) even after controlling for age, sex and BMI (P = 0·016). IGFBP‐1, leptin levels and body composition did not show a difference. When the LGA group was divided into subgroups according to birth weight, the analysis revealed that after controlling for BMI, being an LGA and having a higher birth weight in the upper half were associated with lower adiponectin levels (estimated marginal means of logarithmic adiponectin levels 2·6 ± 0·2 vs. 2·1 ± 0·2 µg/ml, P = 0·042). Conclusion LGA children have higher insulin and lower adiponectin levels than AGA children in spite of similar BMI. Adiponectin is a better indicator of insulin resistance in LGA children at prepubertal ages and is affected by birth weight.     

Correlation of the hypotonic shock response and extent of shape change with the new ThromboLUX™

ThromboLUX (TLX)‐Score was compared with hypotonic shock response (HSR) and extent of shape change (ESC) in 99 samples from 42 platelet concentrates. Tests were performed in parallel and duplicate. Mean values for TLX Score, HSR and ESC were 30·3 ± 3·8%, 69·0 ± 12·2% and 23·2 ± 4·9%, respectively. We found no significant correlation between TLX Score and HSR or ESC (r = ?0·158, P = 0·118 and r = ?115, P = 0·255, respectively), whereas HSR and ESC correlated significantly (r = 0·351, P < 0·001). As TLX Score did not show significant correlation with HSR and ESC, the value of TLX for platelet quality testing remains unclear. Studies comparing these parameters with transfusion outcome are needed.     

Severe hypoleptinaemia associated with insulin resistance in patients with common variable immunodeficiency

Objective Common variable immunodeficiency (CVI) is a primary immunodeficiency syndrome characterized by impaired production of antibodies and recurrent infections. Delay in diagnosis leads to metabolic wastage and low body weight. Leptin, a hormone produced by white adipose tissue, modulates insulin action by signal transduction cross‐talk and by direct action on pancreatic beta‐cells. We hypothesized that patients with CVI might present a defective regulation of leptin production and insulin resistance. Patients Thirteen CVI patients (39 ± 11 years) under gammaglobulin replacement were evaluated in parallel with 13 gender‐, age‐, body weight‐ and body mass index (BMI)‐matched healthy voluntaries, and with data from two large population series, the Bruneck and the Hoorn Studies. Measurements Serum leptin and insulin levels, homeostasis model assessment – insulin resistance (HOMA‐IR), body composition, haematological, biochemical and immunoglobulin measurements were obtained. Data were analysed by a one‐way analysis of variance (anova ) and by Pearson's rank analysis. The institutional ethics committee approved the study, and informed consent was obtained from patients and controls. Results No differences were found between CVI and the control group when comparing gender distribution, age, body weight, BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels were lower (P < 0·05) in CVI patients than in controls and lower than fasting leptin levels detected in a large population study. CVI patients’ serum leptin levels did not correlate with BMI (r = 0·074, P = 0·8) and their high HOMA‐IR indicated insulin resistance. Conclusions CVI patients are relatively hypoleptinaemic and insulin resistant, and their serum leptin levels are not correlated to their BMI.     

Association of race, body fat and season with vitamin D status among young women: a cross-sectional study

Objective The purpose of this study was to provide an estimate of vitamin D status in young women residing in south‐east Texas and to determine factors that predict 25‐hydroxyvitamin D (25‐OHD) concentration. Design A cross‐sectional study was conducted on 800 non‐Hispanic white, non‐Hispanic black, and Hispanic women 16–33 years of age, who were seen in an outpatient clinic. Measurements Information was obtained on race, smoking, exercise and dietary intake of vitamin D. Percentage total body fat (%TBF) was assessed using dual‐energy X‐ray absorptiometry (DXA). Exposure to sunlight was estimated by examining national records of temperature, hours of daylight and UV index for the latitude of the study site. To determine the relationship between 25‐OHD and %TBF, season, race, body mass index (BMI), dietary vitamin D, age and smoking in a multivariate context, stepwise linear regression analysis was performed. Results Serum 25‐OHD levels differed among the racial groups (all pairwise differences P < 0·001), with the lowest value among non‐Hispanic blacks (37·7 nmol/l) and the highest value among non‐Hispanic whites (71·8 nmol/l). Among Hispanics, mean serum 25‐OHD was 47·9 nmol/l. Serum 25‐OHD was negatively associated with %TBF (r = –0·28), BMF (r = –0·36) and TBF (r = –0·33), all P < 0·001, and positively associated with dietary vitamin D (r = 0·10) and pack years of smoking (r = 0·11), both P < 0·01. In the summer months, serum 25‐OHD values were higher (55·4 nmol/l) than in the winter months (48·1 nmol/l), P < 0·001. The final regression model predicting serum 25‐OHD levels included race, %TBF and season (all P < 0·05) and explained 36% of the variance in 25‐OHD. Conclusions Favourable environmental conditions do not result in sufficient vitamin D status for young women, especially non‐Hispanic blacks, Hispanics and the obese.     

Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency

objective To investigate the role of IGF‐1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography. subjects Thirty‐nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF‐1 levels, and 39 sex‐, age‐ and body mass index (BMI)‐matched healthy controls. results Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well‐defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = ?0·82; P < 0·0001) and patients with GHD (r = ?0·84, P < 0·0001), serum IGF‐1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH‐deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF‐1 levels (t = ?9·9, P < 0·001), followed by low density lipoprotein (LDL)‐cholesterol levels (t = ?2·3, P = 0·02). Compared to patients with normal IGF‐1 levels, those with low IGF‐1 levels had lower high density lipoprotein (HDL)‐cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL‐cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH‐deficient patients with low IGF‐1 levels. conclusions GH‐deficient patients have alterations in lipid profile with an increase in the total/HDL‐cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF‐1 deficiency have increased IMT.