Androgens and osteocalcin during the menstrual cycle.

The relationship between physiological variations in female sex and androgenic hormones and calciotropic hormones was investigated during the menstrual cycle. Estradiol, progesterone, total and free testosterone, androstenedione, immunoreactive PTH, calcitonin, osteocalcin (OC), and ionized calcium serum levels were determined throughout the menstrual cycle in a population of healthy eumenorrhoic women (n = 12; age range: 20-29 yr; mean: 24.2 yr). The women were studied from the first day of a menstrual phase until the first day of the following menstrual phase. Cycle length was standardized on the preovulatory estradiol peak (day 0), and values were given for the first day of a menstrual phase, and days -12, -10, -8, -6, -4, -2, 0, 2, 4, 6, 8, 10, 12, and 14 of the menstrual cycle. All subjects had a regular ovulatory cycle, as indicated by the hormonal profile. No significant cycle phase-dependent changes in calciotropic hormones were present. Significant positive correlations between total testosterone (r = 0.32, P < 0.001), free testosterone (r = 0.26, P < 0.001), androstenedione (r = 0.35, P < 0.0001), and OC were observed. The significant relations between these variables were confirmed by a time series analysis. For the first time, these findings indicate a relationship between androgens and OC serum levels during the menstrual cycle. An important regulatory role of endogenous androgens in OC secretion, bone formation, and maintenance of normal bone mineral content in the healthy eumenorrhoic woman is hence suggested.     

Relationship of adiponectin to body fat distribution,insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

AIMS/HYPOTHESIS: Increased intra-abdominal fat is associated with insulin resistance and an atherogenic lipoprotein profile. Circulating concentrations of adiponectin, an adipocyte-derived protein, are decreased with insulin resistance. We investigated the relationships between adiponectin and leptin, body fat distribution, insulin sensitivity and lipoproteins. METHODS: We measured plasma adiponectin, leptin and lipid concentrations, intra-abdominal and subcutaneous fat areas by CT scan, and insulin sensitivity index (S(I)) in 182 subjects (76 M/106F). RESULTS: Adiponectin concentrations were higher in women than in men (7.4+/-2.9 vs 5.4+/-2.3 micro g/ml, p<0.0001) as were leptin concentrations (19.1+/-13.7 vs 6.9+/-5.1 ng/ml, p<0.0001). Women were more insulin sensitive (S(I): 6.8+/-3.9 vs 5.9+/-4.4 x 10(-5) min(-1)/(pmol/l), p<0.01) and had more subcutaneous (240+/-133 vs 187+/-90 cm(2), p<0.01), but less intra-abdominal fat (82+/-57 vs 124+/-68 cm(2), p<0.0001). By simple regression, adiponectin was positively correlated with age ( r=0.227, p<0.01) and S(I) ( r=0.375, p<0.0001), and negatively correlated with BMI ( r=-0.333, p<0.0001), subcutaneous ( r=-0.168, p<0.05) and intra-abdominal fat ( r=-0.35, p<0.0001). Adiponectin was negatively correlated with triglycerides ( r=-0.281, p<0.001) and positively correlated with HDL cholesterol ( r=0.605, p<0.0001) and Rf, a measure of LDL particle buoyancy ( r=0.474, p<0.0001). By multiple regression analysis, adiponectin was related to age ( p<0.0001), sex ( p<0.005) and intra-abdominal fat ( p<0.01). S(I) was related to intra-abdominal fat ( p<0.0001) and adiponectin ( p<0.0005). Both intra-abdominal fat and adiponectin contributed independently to triglycerides, HDL cholesterol and Rf. CONCLUSION/INTERPRETATION: These data suggest that adiponectin concentrations are determined by intra-abdominal fat mass, with additional independent effects of age and sex. Adiponectin could link intra-abdominal fat with insulin resistance and an atherogenic lipoprotein profile.     

Different training patterns and bone mineral density of the femoral shaft in elite, female athletes.

The effects of sporting activity and of menstrual status on the bone mineral content of the femoral mid-shaft were investigated. The cohort consisted of 67 elite, female athletes comprising 21 runners, 36 rowers, and 10 dancers. Twenty five of these athletes were amenorrhoeic, 27 eumenorrhoeic, and 15 were taking the oral contraceptive. The bone mineral content was also measured in 13 eumenorrhoeic, sedentary women. The mean (95% confidence interval) bone mineral content in the runners was 1.51 (1.47 to 1.55) g/cm2, which was significantly higher than in the rowers, dancers, and sedentary controls whose values were 1.43 (1.40 to 1.47), 1.39 (1.33 to 1.45), and 1.40 (1.34 to 1.45) g/cm2 respectively. There was no significant difference in the bone mineral content between the amenorrhoeic, eumenorrhoeic, and oral contraceptive taking athletes. These results may have implications for devising exercise strategies to reduce the possibility of fractures in later life.     

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist increases plasma adiponectin levels in type 2 diabetic patients with proteinuria

Adiponectin appears to be an important modulator for metabolic and vascular diseases. A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2 diabetic patients with proteinuria. Sixty-four patients (mean age, 46.1±4.6 yr; 30 male, 34 female) and 26 healthy volunteers (mean age, 45.3±4.8 yr; 14 male, 12 female) were included. Patients with proteinuria were treated with 4-mg/d rosiglitazone (n = 21, 10 males, 11 females) for 4 wk. Adiponectin levels in patients were significantly lower than those of controls (p<0.001). There were significant negative correlations between adiponectin concentrations and insulin levels as well as homeostasis model assessment (HOMA) index in patient’s group (r=−0.538, p<0.001; r,=−0.393, p=0.001, respectively). There was also a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r=−0.526, p=0.002). Plasma adiponectin levels in patients with proteinuria ?(n=31; 3.91±2.57 μg/mL) were significantly lower than those without proteinuria (n=33; 10.15±1.97 μg/mL) (p<0.001). After the treatment period, adiponectin levels significantly increased (p<0.001) and proteinuria, plasma insulin, and HOMA indexes significantly decreased in treatment group (p<0.001, p<0.001, p<0.001, respectively). The results suggest that adiponectin is inversely correlated with proteinuria and treatment with peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist rosiglitazone both corrects proteinuria and increases the low adiponectin levels in diabetic patients.     

Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years

INTRODUCTION: This study aimed to establish sex- and age-specific reference curves enabling the calculation of z-scores and to examine correlations between bone markers and anthropometric data. METHODS: Morning blood samples were obtained from 572 healthy children and adolescents (300 boys) aged 2 months to 18 yr. Height, weight, and pubertal stage were recorded. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), type-1 collagen degradation markers [carboxyterminal telopeptide region of type I collagen (ICTP), carboxyterminal telopeptide alpha1 chain of type I collagen (CTX)], and tartrate-resistant acid phosphatase (TRAP5b) were measured. Cross-sectional centile charts were created for the 3rd, 50th, and 97th centiles. RESULTS: Apart from TRAP5b, all bone markers were nonnormally distributed, requiring logarithmic (BALP, OC, ICTP) or square root (CTX) transformation. Back-transformed centile curves for age and sex are presented for practical use. All bone markers varied with age and pubertal stage (P < 0.001). Significant correlations were found between sd score (SDS) for bone formation markers BALP and OC (r = 0.13; P = 0.004), SDS for collagen degradation markers ICTP and CTX (r = 0.14; P = 0.002), and SDS for the phosphatases (r = 0.34, P < 0.001). Height and weight SDS correlated weakly with some bone marker SDS, particularly with lnBALP SDS (r = 0.20 and 0.24, respectively; both P < 0.001). CONCLUSION: This study provides reference curves for OC, BALP, CTX, ICTP, and TRAP5b in healthy children. Taller and heavier individuals for age had greater bone marker concentrations, likely reflecting greater growth velocity. SDS for markers of bone formation, collagen degradation, and phosphatases were each independently correlated, suggesting they derive from the same biological processes. The possibility of calculating SDS will facilitate monitoring of antiresorptive therapy or disease progression in children with metabolic bone disease.     

Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity

Adiponectin, a novel adipocytokine with insulin sensitizing properties, is inversely related to obesity and insulin resistance in adults. We recently reported large variations in weight gain and insulin sensitivity during the first year in infants born small for gestational age (SGA) or appropriate for gestational age (AGA). We now determined whether adiponectin levels were related to postnatal growth and insulin sensitivity in a prospective cohort followed from birth to two years old (n = 85) (55 female/30 male, 65 SGA/20 AGA). Serum adiponectin levels at one year and two years were higher compared to reported levels in adults and older children, and decreased from one year (21.6 +/- 0.6 microg/ml) to two years (15.7 +/- 0.7 microg/ml) (p < 0.05). At two years adiponectin levels were lower in females (15.3 +/- 0.4 microg/ml) than males (16.4 +/- 0.6 microg/ml) (p < 0.05), but no gender difference was seen in leptin or insulin levels. No differences in adiponectin levels were seen between SGA and AGA infants at one or two years. However, in SGA infants changes in adiponectin between one to two years old were inversely related to weight gain (r = -0.310, p < 0.05). Changes in leptin levels between one to two years were positively related to weight gain in both SGA and AGA infants (r = 0.450 and r = 0.500 respectively, both p < 0.05). Adiponectin levels were unrelated to insulin levels at one or two years, nor to change in insulin levels between one to two years. In multiple regression analysis, adiponectin levels were related only to postnatal age; omitting age from the model, the determinants of higher adiponectin levels were male gender (p = 0.03), lower postnatal body weight (p < 0.001), and higher birth weight SD score (p = 0.004). In conclusion, fall in serum adiponectin levels during the first two years of life were related to increasing age and greater weight gain SGA infants, but were unrelated to insulin sensitivity.     

Elite volunteer athletes of different sport disciplines may have elevated baseline GH levels divorced from unaltered levels of both IGF-I and GH-dependent bone and collagen markers: a study on-the-field

Seventy-seven Italian eliteathletes(42 M, 35 F, mean age +/- SE: 24.4-0.7 yr, age range: 17-47 yr) of different sport disciplines (sprinters, triathletes, middle-distance runners, road-walkers, cyclists, rowing athletes, skiers, roller hockey players, swimmers) were sampled on-the-field (before a training session) for the determination of basal GH, IGF-I, C-terminal cross-linked telopeptide of type I collagen (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP) levels, two GH-dependent peripheral markers of bone and collagen turnover, respectively. Basal GH concentrations were significantly higher (p<0.001) in female (5.8 +/- 1.0 ng/ml) vs male athletes (1.8 +/- 0.5 ng/ml), with a large spread of values in either gender. Mean GH levels of athletes were significantly higher than those recorded in age-matched sedentary controls (females: 2.5 +/- 0.5 ng/ml, p<0.001; males: 0.5 +/- 0.2 ng/ml, p<0.05). Among female athletes, 7/35 had basal GH values higher than the upper limit of control values (>9.5 ng/ml), while among males 7/42 had values higher than the upper limit of male sedentary controls (>3.6 ng/ml). No significant differences in basal GH concentrations were found between females taking oral contraceptives (OC) and those who did not receive this treatment (5.0 +/- 2.1 vs 6.0 +/- 1.2 ng/ml). IGF-I levels (236.4 +/- 7.8 ng/ml) were in the normal range for age in all athletes (except for 1 athlete with slightly increased levels), no significant correlation being found between GH and IGF-I levels (R2=0.0393). Mean ICTP (4.6 +/- 0.2 ng/ml) and PIIINP (4.4-0.1 ng/ml) concentrations of elite athletes were not significantly different from those recorded in age and matched healthy sedentary subjects; 4 athletes showed increased PIIINP levels and 2 had increased ICTP levels. ICTP and PIIINP levels were positively correlated with chronological age (p<0.001), a positive correlation being also found between the two markers (p<0.001). On the contrary, no significant correlation was found between basal GH/IGF-I levels and ICTP/PIIINP levels. In conclusion, the present study demonstrates that: 1) elite athletes (particularly females), which have frequently increased basal GH on-the-field, have actually normal IGF-I levels; 2) ICTP and PIIINP levels of athletes are similar to those recorded in healthy sedentary, being significantly higher in younger subjects of both groups; 3) the presence of increased basal GH levels, being associated with normal IGF-I, ICTP and PIIINP levels, is probably the result of a transient GH peak in this study group. Further additional studies are requested to verify the possible use of these peripheral GH-dependent markers for detecting exogenous chronic administration of recombinant GH in athletes.     

Adiponectin and stress hormone responses to maximal sculling after volume-extended training season in elite rowers

The purpose of this study was to investigate the resting and short-duration exercise-induced hormone responses of male rowers as a result of 6 months of volume-extended training season. Body composition, maximal aerobic capacity, and on-water 2000-m sculling performance were assessed before and after a 24-week training in elite rowers (n = 11; 193.1 +/- 5.2 cm; 91.6 +/- 5.8 kg; maximum oxygen consumption [VO2max], 6.2 +/- 0.5 L x min(-1)). Six rowers were selected (SEL; 192.0 +/- 6.3 cm; 93.5 +/- 7.1 kg; VO2max, 6.4 +/- 0.4 L x min(-1)) and 5 were not selected (N-SEL; 194.8 +/- 4.1 cm; 89.6 +/- 4.0 kg; VO2max, 6.0 +/- 0.5 L x min(-1)) for the national team. Resting adiponectin did not change as a result of prolonged training. Adiponectin did not change after 2000-m rowing at baseline either. No responses were also observed 24 weeks later in SEL rowers, whereas a significant decrease (P < .05) was observed in N-SEL rowers. At the same time, leptin also decreased after the first 30 minutes of recovery in N-SEL rowers. After the training period, immediate postexercise increases in growth hormone and testosterone were significantly higher in the whole group of rowers. No differences in cortisol responses were observed before and after the training period in SEL and N-SEL rowers. In conclusion, it appears that resting adiponectin does not change as a result of prolonged training. Training may modify adiponectin response to an short-duration exercise depending on the performance level of athletes. Decreased postexercise adiponectin and leptin values in rowers with lower performance capacity may be indicative of the inadequate recovery of these athletes.     

Changes in biochemical markers of osteoblastic activity during the menstrual cycle

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.     

Adiponectin before and after weight loss in obese children

Adiponectin is decreased in obesity and seems to be involved in insulin resistance. The influences of age, gender, puberty, and weight loss on adiponectin have not been studied in obese children. We measured body fat mass based on skinfold thickness, age, pubertal stage, gender, adiponectin, and insulin resistance (homeostasis model assessment) in 42 obese children. We analyzed adiponectin and homeostasis model assessment 1 yr later in these obese children and separated them into two groups according to degree of weight loss (decrease in sd score for body mass index, >or=0.5 vs. <0.5). Adiponectin was negatively correlated to percentage body fat (r = -0.44; P = 0.002), insulin resistance (r = -0.33; P = 0.016), and age (r = -0.41; P = 0.003). Adiponectin levels were significantly (P = 0.017) higher in pubertal girls compared with boys, but there was no significant difference in prepubertal children in respect to gender (P = 0.833). Adiponectin was significantly (P < 0.001) lower in pubertal compared with prepubertal children. The significant weight loss in 16 children was associated with a significant increase in adiponectin (P = 0.010) and a decrease in insulin resistance (P = 0.013), whereas there were no changes in the 26 children without significant weight loss. Adiponectin levels in obese children were negatively correlated to age, body fat, and insulin resistance and were decreased in puberty. Significant weight loss led to an increase in adiponectin levels and an improvement of insulin resistance.     

Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa

BACKGROUND: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Adipokines and insulin play an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown. OBJECTIVE: The aim of the study was to determine whether adipokines and insulin are independently associated with measures of BMD in adolescents with AN and controls. DESIGN/METHODS: Levels of adiponectin and insulin, fasting and after oral glucose, were evaluated in 17 AN patients and 19 controls (age, 12-18 yr), in whom hormonal parameters [GH, IGF-I, cortisol, estradiol, leptin, ghrelin, and peptide YY (PYY)] had been previously determined. Body composition, bone mineral content, and BMD at the lumbar spine, hip, femoral neck, and total body were assessed by dual energy x-ray absorptiometry. Two bone formation and bone resorption markers were examined. SETTING: The study was conducted at a General Clinical Research Center. RESULTS: Adiponectin differed between AN subjects and controls after controlling for fat mass and decreased in both after oral glucose (P = 0.02 and 0.07). On regression modeling, independent associations were observed of: 1) body mass index and adiponectin with lumbar spine bone mineral apparent density Z-scores (r(2) = 0.45); 2) lean mass, PYY, and ghrelin with hip Z-scores (r(2) = 0.55); 3) adiponectin and lean mass with femoral neck-bone mineral apparent density Z-scores (r(2) = 0.34); and 4) lean mass, PYY, GH, and ghrelin with total body-bone mineral content/height Z-scores (r(2) = 0.64), for the combined group. Adiponectin was also independently associated with BMD, and insulin was associated with bone turnover markers in the groups considered separately. CONCLUSIONS: Adiponectin contributes significantly to the variability of bone density, and insulin contributes to bone turnover markers in adolescent girls.     

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.     

Elevated circulating plasma adiponectin in underweight patients with COPD

BACKGROUND: Adiponectin is an adipose tissue-derived specific protein that has antiinflammatory as well as anti-atherosclerotic effects. In the United States, many patients with COPD are obese and die of cardiovascular diseases. However, in Japan, patients with COPD are frequently cachexic and die of respiratory failure. This study was designed to investigate the role of adiponectin in these differences in characteristics of COPD. METHODS: We enrolled normal-weight and underweight male patients with COPD (n = 31; age, 71 +/- 1 years; body mass index [BMI], 20.1 +/- 0.6 kg/m(2)) and age-matched, healthy, male, control subjects (n = 12). The adiponectin levels were measured by enzyme-linked immunosorbent assay. Correlation of adiponectin levels with pulmonary function and serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6) were estimated. RESULTS: Adiponectin levels in patients with COPD were significantly higher than those in control subjects (p<0.01) and inversely correlated with BMI (r = - 0.55, p<0.01). Even in the normal-weight patients with COPD, adiponectin levels were significantly higher than those in control subjects (p<0.01). Adiponectin levels in patients with COPD significantly correlated with percentage of predicted residual volume (r = 0.40, p<0.05). In patients with TNF-alpha levels > 5 pg/mL, there was a significant correlation between plasma adiponectin and serum TNF-alpha levels (r = 0.68, p<0.05). CONCLUSIONS: Plasma adiponectin levels in patients with COPD were elevated and correlated with body weight loss, hyperinflation, and systemic inflammation. Increased adiponectin may reduce cardiovascular events in underweight patients with COPD.     

Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and cardiovascular risk factors in middle-aged men

Adiponectin, an adipocyte-derived protein, seems to be a link between obesity, insulin resistance, and atherosclerosis. The present study investigated the association between adiponectin and coronary artery disease in middle-aged men. Material and methods: We examined 48 men (aged 40–60) with angiographically confirmed coronary atherosclerosis and 19 healthy men, matched by age, as a control group. Concentrations of glucose and lipids were estimated with enzymatic methods. Plasma level of adiponectin, total and free testosterone, estradiol, estrone, DHEA-S, and insulin were estimated with RIA commercial kits. Results: Men with coronary atherosclerosis had lower plasma adiponectin level than controls (16.2±9.2 vs 20.5±6.7 μg/mL; p<0.05). However, after including BMI and waist as covariate data in ANCOVA, the difference in adiponectin levels between men with CAD and controls lost statistical significance (respectively for BMI and waist: p=0.4 and p=0.7). Moreover, although not significant, adiponectin levels decreased as a function of the number of significantly narrowed coronary arteries. In a priori comparison the lowest adiponectin plasma concentration was in men with three-vessel coronary artery disease (14.3±9.8 μg/mL) and the highest in controls (20.5±6.8 μg/mL; p=0.09). Adiponectin plasma level correlated negatively (p<0.05) with BMI, waist, percentage of total fat, fasting-insulin-resistance index (FIRI), total cholesterol and triglycerides, and positively with quantitative insulin sensitivity check index (QUICKI), HDL cholesterol, total testosterone, and total testosterone/estradiol ratio. Conclusions: Our data suggest that low plasma adiponectin level is connected with insulin resistance syndrome and atherogenic lipid profile. It seems that adiponectin plays a role in pathogenesis of coronary atherosclerosis, especially in obese and insulin-resistant subjects.     

Adiponectin, hepatocellular dysfunction and insulin sensitivity

OBJECTIVE: Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects. DESIGN: Cross-sectional, population-based study dealing with diabetes prevalence in northern Spain. PATIENTS: Two hundred and fifty-seven apparently healthy Caucasian subjects consecutively enrolled in the study. MEASUREMENTS: Adiponectin serum levels were measured by enzyme-linked immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and insulin resistance by the homeostasis model of assessment (HOMA value). RESULTS: Adiponectin levels were negatively correlated with alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT), before and after adjustment for sex, age, body mass index (BMI) and insulin resistance (ALT; r = -0.32, P < 0.001; adjusted: r = -0.13, P = 0.033; GGT; r = -0.31, P < 0.001; adjusted: r = -0.16, P = 0.011). Additionally, adiponectin correlated with alkaline phosphate (ALKP) only after adjusting for the same confounding variables (r =-0.10, P = 0.098; adjusted: r = -0.14, P = 0.031). A general linear model, adjusting for age, sex and BMI, was constructed to predict the decrease in circulating adiponectin for each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value above the median, serum adiponectin decreased by -0.97 mg/l (95% CI -1.46 to -0.48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin resistance, predicted serum concentrations of both ALT and GGT, explaining 19% and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or insulin resistance, explained 20% of ALKP variance. CONCLUSIONS: Adiponectin levels are associated in healthy humans with plasma concentrations of various liver function tests. The contributions of adiponectin to maintaining liver integrity through the regulation of both insulin sensitivity and/or the inflammatory response merit further studies.     

Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices

HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidemia, and insulin resistance. Adiponectin is an adipose-derived peptide thought to act as a systemic regulator of glucose and lipid metabolism. We investigated adiponectin concentrations in 10 HIV-infected patients during acute HIV infection (viral load, 2.0 x 10(6) +/- 1.0 x 10(6) copies/ml) and then 6-8 months later, as well as cross-sectionally in 41 HIV-infected patients (21 with evidence of fat redistribution and 20 without evidence of fat redistribution) in comparison with 20 age- and body mass index-matched healthy control subjects. Circulating adiponectin concentrations did not change with treatment of acute HIV infection (5.8 +/- 0.4 vs. 5.9 +/- 0.7 micro g/ml, P = 0.96) but were reduced in patients with chronic HIV infection and fat redistribution (7.8 +/- 0.9 micro g/ml), compared with age- and body mass index-matched HIV-infected patients without fat redistribution (12.7 +/- 1.7 micro g/ml) and healthy control subjects (11.9 +/- 1.7 micro g/ml, P < 0.05 vs. HIV-infected patients without fat redistribution and vs. control subjects). Adiponectin concentrations correlated with body composition [correlation coefficient (r) = -0.47, P = 0.002 vs. trunk fat:total fat; r = 0.51, P < 0.001 vs. extremity fat:total fat], insulin response to glucose challenge (r = -0.36, P = 0.03), triglyceride (r = -0.39, P = 0.01), and high-density lipoprotein (r = 0.37, P = 0.02) among the HIV-infected patients. Adiponectin remained a significant correlate of insulin response to GTT, controlling for medication use and body composition changes in HIV-infected patients. These data suggest a strong relationship between adiponectin and body composition in HIV-infected patients. Changes in adiponectin may contribute to the metabolic dysregulation in this group of patients.     

Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients

BACKGROUND/AIMS: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. METHODS: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5+/-15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41+/-31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6+/-12.1 years). BMI (kg/m(2)) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. RESULTS: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2+/-6.2 vs. 3.9+/-1.8 ng/ml; p<0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2+/-6.2 vs. 18.7+/-5.0 ng/ml; p=0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4+/-21.5 vs. 10.5+/-5.9 microg/ml; p<0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r=-0.527, p=0.002), the HOMA-R (r=-0.378, p<0.05) and the fasting insulin levels (r=-0.397, p<0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2+/-3.9 mmol.microIU/ml; r=-0.098, p=0.59), insulin levels (13.3+/-14.4 mU/l; r=-0.073, p=0.69), glucose levels (89+/-13 mg/dl; r=-0.049, p=0.78), BMI (25.6+/-3.7 kg/m(2); r=-0.041, p=0.82) and body fat content (26.4+/-8.4%; r=-0.018, p=0.94) on the other hand. CONCLUSION: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.     

Is adiponectin level a predictor of nonalcoholic fatty liver disease in nondiabetic male patients？

AIM: To study the levels of adiponectin in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD) in comparison with control group. METHODS: Thirty-five patients who had elevated serum aminotransferase levels with bright liver and 34 healthy volunteers without liver disease were evaluated. Age, gender and body mass index (BMI) were recorded. Fasting plasma glucose, insulin, adiponectin, proinsulin and lipid profile were measured. A standard oral glucose tolerance test (OGTT) with insulin response was performed and the index of insulin resistance was calculated according to the homeostasis model assessment (HOMA) method. RESULTS: According to the OGTT results, none of the participants had diabetes. Serum adiponectin levels were statistically significantly lower in patients with NAFLD than in control group (8.14±3.4μg/mL vs 12.4±9.4μg/mL, respectively, P<0.01). A statistically significant correlation was found between adiponectin and BMI (r: -0.33, P<0.01), HOMA (r: -0.26, P<0.05), proinsulin (r:-0.32, P<0.01), AST (r: -0.25, P<0.05), ALT (r: -0.26, P<0.05) or GGT (r: -0.22, P<0.05). In multiple regression analysis models, adiponectin levels were the only predictor of NAFLD in males, whereas in female group it was the BMI. CONCLUSION: Low adiponectin level might be a predictor of NAFLD especially in male nondiabetics.     

Adiponectin and inflammatory markers in peripheral arterial occlusive disease

This study was designed to examine the plasma levels of adiponectin as well as markers of inflammation and endothelial function in peripheral arterial occlusive disease (PAOD), and to investigate the pathophysiological significance of adiponectin in this disease. Eighty-eight subjects with (n=40) and without PAOD (n=48) were enrolled. Multiple regression analysis including age, sex, body mass index, hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, creatinine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecules-1 (sVCAM-1), von Willebrand factor, and high-sensitive C reactive protein (Hs-CRP) showed that adiponectin concentration was significantly lower in PAOD subjects (PAOD: 7.9+/-0.7 microg/mL versus without PAOD: 9.5+/-0.6 microg/mL, F=4.94, p<0.03). Furthermore, concentrations of adiponectin (F=8.5, p<0.01) as well as sICAM-1 (F=5.8, p<0.02), sVCAM-1 (F=5.9, p<0.02), and Hs-CRP (F=3.8, p=0.05) were independently associated with ankle-brachial index. In 27 subjects (10 with PAOD and 17 without PAOD), adiponectin levels in the femoral artery and saphenous vein were measured. A significant step-up of adiponectin from the artery to the vein was observed in subjects without PAOD (+13.0%, p<0.01), but not in subjects with PAOD (+0.4%, NS). Plasma adiponectin as well as Hs-CRP were followed before and after percutaneous transluminal angioplasty (PTA) in eight patients. Adiponectin showed a tendency to decrease after PTA (day 6, -30.6%), although Hs-CRP significantly increased. Adiponectin is decreased in patients with PAOD in proportion to the severity of the disease. Adiponectin concentration could be a marker of the existence of atherosclerosis, and measurement of its concentration may be helpful in assessment of the progress of atherosclerosis.     

Low adiponectin levels in adolescent obesity: a marker of increased intramyocellular lipid accumulation

We examined the impact of adolescent obesity on circulating adiponectin levels and the relationship between adiponectin and insulin sensitivity, intramyocellular (IMCL) lipid content, plasma triglycerides, and free fatty acids. Plasma adiponectin levels were measured in 8 nonobese (percentage fat, 18 +/- 1.8) and 14 obese adolescents (percentage fat, 41 +/- 1.6). Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Intramuscular lipid content was quantified using (1)H-nuclear magnetic resonance spectroscopy, and abdominal fat distribution by magnetic resonance imaging. Adiponectin levels were lower in obese adolescents (9.2 +/- 1 microg/ml, P < 0.001) and were positively related to insulin sensitivity in all subjects (r = 0.531, P < 0.02). Strong inverse relationships were found between adiponectin and triglyceride levels (r = -0.80, P < 0.001) and IMCL (r = -0.73, P < 0.001). Triglycerides (partial r(2) = 0.52; P < 0.0002) and IMCL (partial r(2) = 0.10; P < 0.05) were the most significant predictors of adiponectin levels, explaining 62% of the variation. In conclusion, plasma adiponectin levels are reduced in adolescent obesity and related to insulin resistance, independent of total body fat and central adiposity. There is a strong relationship between adiponectin and IMCL lipid content in this pediatric population. The putative modulatory effects of adiponectin on insulin sensitivity may, in part, be mediated via its effects on IMCL lipid content.