Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study

OBJECTIVE: Androgens and oestrogens have opposing effects on some adipocyte functions. Thus, the androgen to oestrogen balance may be as important as the individual hormones in determining the biological interaction between endogenous sex hormones and adipocyte-derived factors such as adiponectin and leptin. We tested this hypothesis by evaluating the sex-specific, cross-sectional association of sex hormones and androgen to oestrogen ratios with serum adiponectin and leptin in older men and postmenopausal women. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1510 community dwelling men and postmenopausal women aged 50-92 years. MEASUREMENTS: Serum leptin, adiponectin and sex hormone levels. RESULTS: Adiponectin and leptin levels were higher in women than men (P < 0.001). In both sexes, adiponectin concentrations were lower, and leptin levels higher, with increasing BMI and waist girth (all P < 0.001). Although the ratio of total testosterone to total oestradiol was significantly associated with both adipocytokines in both sexes, the strongest and most consistent hormone-adipocytokine associations were observed when the androgen to oestrogen ratio was expressed as total testosterone to bioavailable oestradiol. In linear regressions, the testosterone to bioavailable oestradiol ratio was positively related to adiponectin and inversely related to leptin, with nearly identical standardized beta-coefficients for men and women (all P < 0.001). The strength of the hormone ratio-adipocytokine associations was reduced, but not eliminated, after adjustment for age, adiposity and cardiovascular disease risk factors, including insulin resistance. CONCLUSIONS: The striking similarity of the hormone ratio-adipocytokine associations for men and women, despite wide differences in sex hormone and adipocytokine levels, suggests these results reflect underlying physiological mechanisms common to both sexes.     

Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposity

OBJECTIVE: Adiponectin is negatively associated with leptin, insulin and obesity in children and adults. Whereas increases in fetal insulin and leptin are associated with increased weight and adiposity at birth, the role of adiponectin in fetal growth has not yet been determined. The aims of this study were to examine the relationships between adiponectin and insulin, leptin, weight and adiposity at birth in healthy term infants. DESIGN AND METHODS: Anthropometric parameters including weight, length, circumferences and skinfold thickness were measured, and plasma lipid profiles, insulin, leptin and adiponectin concentrations in cord blood samples from 226 singleton infants born at term after uncomplicated pregnancies were assayed. RESULTS: Cord plasma adiponectin, leptin and insulin levels correlated significantly and positively with birthweight (P = 0.001, P < 0.001, P < 0.001, respectively) and the sum of skinfold thicknesses (P < 0.001, P < 0.001, P < 0.001, respectively). Mean cord plasma adiponectin and leptin levels, but not insulin level, were significantly higher in large-for-gestational-age (LGA) infants compared with appropriate-for-gestational-age (AGA) infants. Cord plasma leptin concentration, but not adiponectin concentration, was significantly higher in female infants than in male infants (P = 0.003 and P = 0.94, respectively). Cord plasma adiponectin concentration correlated positively with leptin level (P = 0.007) but not with insulin level (P = 0.78). CONCLUSIONS: High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth.     

Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients

BACKGROUND: The effect of statins on insulin resistance is controversial and poorly studied in nondiabetic subjects. In addition, the effect of statins on leptin and adiponectin has never been studied. METHODS: Forty healthy nondiabetic volunteers (22 men and 18 women) aged 28 to 72 were randomized either to placebo or pravastatin 40 mg daily for a 12-week period. Insulin resistance, assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI), as well as serum leptin and adiponectin levels, was measured at baseline and at the end of therapy. RESULTS: Pravastatin treatment decreased total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels by 24%, 32%, and 14%, respectively ( P < .05 for all), but did not affect glucose and insulin levels, the (QUICKI) index, and adiponectin and leptin levels. When stratification was performed according to QUICKI index or sex, no significant differences were observed in the prevalues and postvalues of leptin, adiponectin, or QUICKI index in the pravastatin group. Adiponectin, leptin, and QUICKI index were statistically higher in women than in men ( P < .001 for both variables). Adiponectin was negatively correlated with body mass index (BMI; r = -0.39, P < .05) and positively correlated with the QUICKI index ( r = 0.54, P < .001) and with high-density lipoprotein cholesterol ( r = 0.50, P < .01). The relation between adiponectin and QUICKI index remained significant after adjustment for sex and BMI ( P = .005 and P = .007, respectively). Leptin was only related to BMI ( r = 0.57, P < .001) and to sex ( P < .001) with no significant correlations with lipid parameters or QUICKI index. Both sex and BMI are independent predictors of leptin ( P < .001 and P < .001). CONCLUSION: A 12-week treatment with pravastatin 40 mg/d does not change the QUICKI index and leptin and adiponectin levels in healthy volunteers. In addition, our results emphasize the importance of sex and BMI in the determination of both adiponectin and leptin. Adiponectin was also related to QUICKI index, whereas this relation was not found with leptin.     

Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes

Aims Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth‐hormone‐secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels. Methods Twelve healthy non‐diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 ± 4.7 years (mean ± sd ), BMI 25.2 ± 3.7 kg/m²; T1DM: age 31 ± 5.5 years, BMI 27 ± 3.1 kg/m²] were similar in the groups. HbA_1c in T1DM was 6.2 ± 1.1% at 20 weeks, 6.3 ± 1.1% at 30 weeks’ gestation and 7.8 ± 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB‐R) levels were measured at 20 and 30 weeks’ gestation and postpartum and determined by radioimmunoassay. Results All pregnancies resulted in full‐term singleton births with no differences in birth weight between groups [T1DM: 3.4 ± 0.56 kg (mean ± SE); ND: 3.6 ± 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers’ weight (T1DM: 458 ± 36 pg/ml and 432.9 ± 26.6 pg/ml; ND: 562 ± 52 pg/ml and 515.8 ± 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB‐R and FL levels declined at 30 weeks’ gestation in T1DM (P = 0.04) but not in ND. Conclusion In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.     

Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function

OBJECTIVE: Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. PATIENTS AND MEASUREMENTS: We studied 20 patients with hyperthyroidism (16 women and 4 men; mean age 47.2 +/- 3.9 years) and 20 patients with hypothyroidism (17 women and 3 men; 51.5 +/- 4.1 years). A group of 20 euthyroid subjects served as control group. Patients were evaluated at the time of diagnosis and again after normalization of thyroid function with appropriate therapy. Serum concentrations of free T4 (FT4), total T3, TSH, insulin, leptin, adiponectin and resistin were measured in all subjects. RESULTS: Hyperthyroid patients showed significantly decreased leptin levels in comparison with controls (11.0 +/- 1.1 vs. 30.4 +/- 5.0 microg/l, P < 0.001). No significant differences in adiponectin levels between hyperthyroid and control groups were found (27.8 +/- 4.0 vs. 46.0 +/- 12.0 mg/l, NS). Patients with hyperthyroidism exhibited reduced resistin levels in comparison with euthyroid subjects (6.4 +/- 0.8 vs. 8.4 +/- 0.7 microg/l, P < 0.05). Normalization of circulating thyroid hormone was accompanied by a nonsignificant increase in leptin levels (12.9 +/- 1.7 microg/l, P < 0.01 vs. control) and no significant modification both in adiponectin (32.0 +/- 7.1 mg/l, NS) and resistin (5.4 +/- 0.7 microg/l, NS) levels. Adjustment of adipocytokine concentrations for body mass index (BMI) showed that treatment of hyperthyroidism induced a significant reduction in adjusted resistin concentrations (0.21 +/- 0.03 vs. 0.28 +/- 0.03 microg/l/BMI units, P < 0.05), with no changes in adjusted leptin and adiponectin. Hypothyroid patients showed significantly lower leptin levels compared with the controls (16.0 +/- 3.5 vs. 30.4 +/- 5.0 microg/l, P < 0.05). Adiponectin levels in patients with hypothyroidism (71.8 +/- 16.0 mg/l) were similar to those in the control group and were not modified with therapy. Resistin levels were significantly reduced among hypothyroid patients (5.8 +/- 1.0 microg/l, P < 0.05), and were not increased after levothyroxine therapy. A significant rise in BMI-corrected leptin levels was observed after replacement therapy, with no changes in adiponectin- and resistin-corrected values. CONCLUSIONS: The results suggest that (1) low serum leptin levels are present in both hyperthyroid and hypothyroid patients but are only increased after therapy in the latter; (2) resistin might be implicated in the insulin resistance state that accompanies thyrotoxicosis; and (3) inadequate secretion of adiponectin seems to have no role in metabolic changes associated with thyroid dysfunction.     

Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids

OBJECTIVES: To investigate the circulating levels of adiponectin, resistin, interleukin 6 (IL-6), and leptin/receptor ratio in healthy Spanish children throughout the different stages of pubertal development. To analyze the relationship between adipokines and sex steroid level changes during puberty. STUDY DESIGN: Serum adiponectin, resistin, IL-6 levels, and leptin/receptor ratio were studied in 160 healthy Spanish children grouped according to their pubertal stage (Tanner I, 23 girls and 22 boys; Tanner II, 19 girls and 16 boys; Tanners III and IV, 21 girls and 20 boys; and Tanner V, 20 girls and 19 boys). In addition, circulating levels of sex hormone-binding globulin (SHBG) were determined in every subject, and testosterone and estradiol levels in boys and girls respectively. RESULTS: Adiponectin levels decreased in boys from mid puberty (P < 0.05) to become significantly lower than in girls (P < 0.001), whereas IL-6 decreased in both sexes (P < 0.05). Resistin levels and leptin/receptor ratio showed no differences between sexes or according to pubertal stage, except in adult females, who had the highest levels of both parameters (P < 0.001). Serum IL-6 levels correlated significantly (P < 0.05) with testosterone and estradiol levels (r=-0.37 and -0.42 respectively), whereas estradiol, but not testosterone, correlated with leptin/receptor ratio (r=0.59; P < 0.001). Furthermore, a positive relationship was found between SHBG and adiponectin and IL-6 (P < 0.001 and P < 0.05 respectively). In addition, a direct correlation between leptin/receptor and body mass index was found in both sexes (P < 0.001). CONCLUSION: Variations in adipokine profiles throughout pubertal development appear to be related with progression of gonadal function.     

2型糖尿病合并高血压患者血浆脂联素的变化

目的探讨2型糖尿病(T2DM)患者、DM合并高血压患者中血浆脂联素水平的变化。方法选取T2DM患者62例、T2DM合并高血压患者41例、健康对照者35名作为研究对象。测定受试者血浆脂联素水平、身高、体重等,比较脂联素水平的改变,以及与其他因素的相关性。结果T2DM患者血浆脂联素明显低于正常对照组(P<0.001),DM合并高血压者血浆脂联素又明显低于DM无高血压者(P<0.01)。在DM患者中,血浆脂联素与收缩压呈负相关(P<0.001)。结论T2DM患者血浆脂联素明显降低,T2DM合并高血压者血浆脂联素水平更低,脂联素在高血压发病过程中起一定作用。     

Leptin and adiponectin in pancreatic cancer: connection with diabetes mellitus

The aim of this study was to analyze the relationship of serum leptin as well as adiponectin and the manifestation of pancreatic cancer (PC). Serum leptin, adiponectin, glucose homeostasis and insulin resistance (expressed as HOMA-IR) were investigated in 64 patients with newly diagnosed PC and compared with 64 healthy controls (CON group) and 75 patients with type 2 diabetes (DM2). Seventy percent of newly diagnosed PC patients had DM2. The levels of leptin were lower, whilst adiponectin/leptin ratio was higher in PC patients (both with and without DM2), in comparison with CON and DM2 groups (P < 0.001) independently of age, BMI and waist circumference. Newly diagnosed PC is characterized with lower leptin concentrations and higher adiponectin/leptin ratio in comparison with CON or DM2 individuals. Analysis of these parameters could help in the screening of persons in high risk for PC, especially in those with DM2. Keywords: adiponectin, leptin, pancreatic cancer, type 2 diabetes mellitus.     

Leptin and adiponectin levels in middle-aged postmenopausal women: associations with lifestyle habits, hormones, and inflammatory markers--a cross-sectional study

To investigate the relationships between blood levels of leptin or adiponectin and lifestyle habits, hormones, and inflammatory markers, we measured parameters of alcohol intake, smoking, physical activity, and blood levels of leptin, adiponectin, testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, thyroxin, C-reactive protein (CRP), and interleukin 6 and interleukin 2 receptor in 76 healthy middle-aged postmenopausal women. Anthropometric measures and body composition (evaluated by dual-energy x-ray absorptiometry) and lipid profiles were also assessed. By simple regression, leptin correlated positively with fat and lean masses, glucose, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and negatively with high-density lipoprotein cholesterol. Adioponectin correlated negatively with fat and lean masses and low-density lipoprotein cholesterol, and positively with high-density lipoprotein cholesterol. Leptin concentration was correlated inversely with adiponectin (r = -0.26, P < .05) and positively with CRP (r = 0.56, P < .01). Adiponectin concentration was negatively correlated with time since last alcoholic drink (r = -0.24, P < .05) and CRP (r = -0.27, P < .05) and positively with testosterone level (r = 0.23, P < .05). By multiple regression analysis, leptin concentration was predicted by age (P < .05), testosterone (P < .05), adiponectin (P < .05), CRP (P < .01), and interleukin 6 receptor (P < .01). Adiponectin concentration was predicted by the time since last alcoholic drink (P < .05), testosterone (P < .05), leptin (P < .05), and C-reactive protein (P = .05). Similar results were found when leptin or adiponectin concentration was adjusted for fat mass. These results suggested that levels of leptin and adiponectin in middle-aged postmenopausal women are partially determined by sexual hormones and inflammatory marker levels, and both predicted one another. Moreover, adiponectin level may be modulated by alcohol intake.     

Increased Resistin Serum Concentrations in Patients with Type 1 Diabetes Mellitus

Objective: Adiponectin, leptin, and resistin are adipokines which play a significant role in the regulation of lipid and carbohydrate metabolism in patients with type 2 diabetes, while little is known about their role in type 1 diabetes mellitus (T1DM). The aim of this study was to measure serum adiponectin, leptin, and resistin levels and to investigate their relationships with some parameters in patients with T1DM and healthy controls.Methods: Fifty children and adolescents with T1DM (21 boys and 29 girls) and 33 healthy control subjects (18 boys and 15 girls) participated in the study. All subjects were patients followed in the Pediatric Endocrinology and Metabolism Unit of Gaziantep University Faculty of Medicine. None of the subjects had hypertension, obesity, hyperlipidemia, anemia, or infection. Adiponectin, leptin, and resistin levels were analyzed with ELISA.Results: There were no statistically significant differences related with age, sex, pubertal status, or body mass index distribution between the diabetic and control groups. Resistin levels were significantly higher in the diabetic group compared to controls (5.26±3.15 ng/mL vs. 3.50±1.26 ng/mL; p<0.01).Conclusion: Of the three investigated adipokines, only resistin was associated with T1DM. Resistin may play a role in the process of inflammation and also in the pathophysiology of T1DM. Conflict of interest:None declared.     

Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios

OBJECTIVE: Whether the adipocyte-derived protein adiponectin is associated with insulin resistance independently of the effects of adiposity and the diabetic state is an important question. We explored, in a cross-sectional study of 486 Japanese nondiabetic women, the relationship between the calculated insulin resistance (homeostasis model assessment ratio (HOMA-R)) and adiponectin levels determined using a validated sandwich ELISA. DESIGN AND METHODS: All participants were stratified into tertiles for HOMA-R (approximately <1.5, 1.5< or = approximately <3.0, 3.0< or = approximately ) and the differences across tertiles of continuous variables were tested with ANOVA. Two-way ANOVA was used to determine possible relationships for plasma adiponectin between tertiles of HOMA-R and several stratified parameters. Multiple regression analyses were performed with HOMA-R or fasting serum insulin as dependent variable, and diastolic blood pressure (BP), body mass index (BMI), serum triglyceride (TG), leptin and adiponectin as independent determinants. RESULTS: Mean plasma adiponectin in the high HOMA-R group decreased compared with that in the low HOMA-R group both before (mean+/-s.e.m. 6.2+/-0.6 vs 9.2+/-0.3 microg/ml, P<0.001) and after adjustment for body fat mass (BFM) as kg or percent (0.31+/-0.04 vs 0.69+/-0.03, 0.18+/-0.02 vs 0.34+/-0.01, both P<0.001). HOMA-R was inversely associated with adiponectin levels both before (r=-0.37, P<0.001) and after adjustment for BFM (r=-0.49, -0.46, both P<0.001). After covariate adjustment for age, diastolic BP, BMI and serum TG, HOMA-R retained a significant correlation with adiponectin/BFM (kg). Both adiponectin and leptin were the significant determinants of HOMA-R or fasting insulin in multiple regression models. CONCLUSIONS: Adiponectin was inversely associated with insulin resistance in nondiabetic subjects, independently from age, BP, adiposity and serum lipids. Because adiponectin is thought to have an anti-atherogenic action, the presence of hypoadiponectinemia may predispose subjects to atherosclerosis, and may progress the atherogenesis in insulin resistance.     

Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men

OBJECTIVE: The relationships between adipocytokines, sex steroids and the GH/IGF-I axis is poorly studied and subject to controversy in healthy elderly male subjects. We investigated the association between both adiponectin and leptin, and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex steroids and IGF-I in healthy non-diabetic Lebanese men. DESIGN AND METHODS: In this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and above (mean age 59.3 +/- 7 years) had a detailed clinical and biological evaluation. Subjects were classified according to the National Cholesterol Education Program criteria of the MetS. Insulin sensitivity was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Subjects with the MetS had lower adiponectin and higher leptin levels (P < 0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with waist size, triglycerides, high-density lipoprotein (HDL) cholesterol and QUICKI (r = -0.33, -0.26, 0.45 and 0.36 respectively, P < 0.0001 for all variables). The relation between adiponectin and HDL cholesterol, triglycerides and QUICKI remained significant after adjustment for age and body mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI (r = 0.63 and -0.63 respectively, P < 0.001 for both variables). However, its relation to the lipid profile was weak (for cholesterol r = 0.16, P < 0.05; for triglycerides r = 0.17, P < 0.05) and disappeared after adjustment for BMI. Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r = 0.39, P < 0.001) and inversely correlated with free-androgen index (r = -0.24, P < 0.01), estradiol and dehydroepiandrosterone sulfate (r = -0.165, P < 0.05; r = -0.21, P < 0.01 respectively). This difference remained significant for SHBG after adjustment for age and BMI (r = 0.20, P < 0.005). Finally, leptin was inversely correlated with total testosterone and SHBG (r = -0.44, P < 0.001; r = -0.30, P < 0.001 respectively); the relation with testosterone remained significant after adjustment for BMI. No significant relationship of either adiponectin or leptin with GH or IGF-I values was observed. In a stepwise multiple regression analysis, the independent predictors of adiponectin were HDL cholesterol, QUICKI, age and BMI (P < 0.0001, P = 0.005, P = 0.002 and P = 0.047 respectively) while for leptin, it was QUICKI, waist size and testosterone (P < 0.0001, P < 0.0001 and P = 0.004 respectively). The adjusted R2 values were 0.34 and 0.55. CONCLUSION: Our results show that in a healthy elderly male population, both adiponectin and leptin are related to insulin sensitivity, independent of age and BMI. While adiponectin is independently related to triglycerides and HDL cholesterol, the weak relationship of leptin to the lipid profile is completely mediated by BMI. In addition, and more interestingly, both adipocytokines are strongly associated with sex steroids. We speculate that SHBG is regulated by adiponectin and that there is an inhibitory effect of testosterone on the adiponectin gene. Further studies are needed to fully elucidate these relationships.     

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN: Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration. PATIENTS: Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months. MEASUREMENTS: Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR). RESULTS: Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation. CONCLUSIONS: Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.     

Adiponectin, total antioxidant status, and urine albumin excretion in the low-risk “Golden Years” type 1 diabetes mellitus cohort

Adiponectin is associated with inflammation and oxidative stress. Levels are reduced in type 2 diabetes mellitus and coronary heart disease. Conversely, levels are elevated in type 1 diabetes mellitus (T1DM) and associated with microalbuminuria and diabetic nephropathy. An explanation may be that elevated adiponectin in T1DM represents a beneficial counterregulatory response to disease. Our aim was to examine adiponectin in relation to urinary albumin excretion and plasma total antioxidant status (TAOS) in subjects with long-standing T1DM. Serum adiponectin and plasma TAOS were measured in 338 samples from the Golden Years cohort. These subjects have T1DM for at least 50 years and are at low risk of complications. Subjects were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria groups. Adiponectin was elevated in women (20.53 ± 5.94 vs 11.8 ± 3.6 mg/L, P < .001); therefore, the samples were sex stratified. Within men, adiponectin was higher in those with macroalbuminuria (normoalbuminuria vs microalbuminuria vs macroalbuminuria: 10.97 ± 3.26 vs 11.55 ± 3.50 vs 23.63 ± 7.07 mg/L, P = .002). In women, no difference was observed (20.48 ± 5.61 vs 20.75 ± 7.04 vs 29.62 ± 7.81 mg/L, respectively; P = .42). Plasma TAOS did not differ by groups. The correlation between adiponectin and TAOS showed a linear increase from normoalbuminuria, microalbuminuria, to macroalbuminuria in men (r = 0.33, P = .001; r = 0.48, P < .001; r = 0.59, P = .04) and women (r = 0.25, P = .01; r = 0.63, P < .001; r = 0.79, P = .08). Adiponectin was higher in women. Within men, levels were significantly higher in the presence of macroalbuminuria. In both sexes, adiponectin and TAOS were correlated, which was most marked with micro-/macroalbuminuria. The increase in adiponectin in the face of an insult may be a compensatory mechanism to reduce oxidative burden.     

Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus

CONTEXT: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. OBJECTIVE: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin. Furthermore, we wished to examine the expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human hypothalamus. METHODS: For this purpose, serum and CSF samples were collected from 20 men and 19 women matched for age [men, 69.8 +/- 8.6 yr (mean +/- SD); women, 69.4 +/- 4.3 yr] and BMI (men, 29.4 +/- 3.4 kg/m(2); women, 27.3 +/- 4.8 kg/m(2)) undergoing elective surgery under spinal anesthesia. RESULTS: Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas resistin and leptin levels were 100-fold less. Unlike their serum levels, adiponectin CSF levels showed no gender difference or correlation with insulin resistance, which is similar to resistin CSF levels. The adiponectin and leptin CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI association with inverse correlation in women (r = -0.61; P = 0.02) and no correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in the paraventricular nucleus, which is involved in energy regulation. CONCLUSION: In summary, our findings show both the presence of adiponectin and resistin in human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of adiponectin and leptin in women appears to be impaired in obesity.     

The tumour necrosis factor (TNF)-alpha system is activated in accordance with pulse pressure in normotensive subjects with type 1 diabetes mellitus

OBJECTIVE: Pulse pressure (PP) and inflammation are important predictors of cardiovascular disease (CVD), even in the normotensive. The age-related increase in PP can be diagnosed up to 20 years earlier in subjects with type 1 diabetes mellitus (T1DM) than in the general population. Some evidence suggests that PP can stimulate inflammation. Our aim was to study the relationship between PP and plasma inflammatory proteins in normotensive subjects with T1DM. DESIGN: This was a cross-sectional study of a group of normotensive (<140/80 mmHg) subjects diagnosed with T1DM 14 years before. None of them had clinically proven CVD or inflammatory conditions or were on antiplatelet, antihypertensive, anti-inflammatory or lipid-lowering treatment. METHODS: The following information was recorded: sex, age, body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), PP, mean blood pressure (MBP), smoking, alcohol intake, insulin dose, lipid profile, HbA1c, microvascular complications, and plasma concentrations of soluble receptor types 1 and 2 of tumour necrosis factor (TNF)-alpha (sTNFR1 and sTNFR2, respectively), interleukin-6, C-reactive protein, adiponectin and leptin. RESULTS: A total of 112 subjects were evaluated (aged 27.4+/-6.6 years, 52.7% women, BMI: 20.4+/-2.7 kg/m2, WHR: 0.82+/-0.09, SBP: 112+/-12 mmHg, DBP: 68+/-9 mmHg, PP: 45+/-9 mmHg, MBP: 82+/-9 mmHg, HbA1c: 8.2% (7.3-9.0%), 41.1% microvascular complications). After adjusting for potential confounders, only inflammatory markers of the TNF-alpha system correlated significantly with PP (Pearson correlation coefficient between sTNFR1 and PP: r = 0.215, P = 0.030; and between PP and sTNFR2: r = 0.238, P = 0.020). CONCLUSION: In normotensive subjects with T1DM after 14 years of diagnosis, the activation of the TNF-alpha system is positively associated with PP levels. This finding might suggest a pathogenic role of the TNF-alpha system in the development of cardiovascular disease in T1DM.     

Down-regulation of adiponectin in patients with familial Mediterranean fever during attack-free period

To evaluate the circulating levels of adipokines (leptin and adiponectin) and ghrelin in patients with familial Mediterranean fever (FMF) and also to assess the relationships between these molecules and disease-related parameters. Forty-eight FMF patients in attack-free period (31 men, [M], 17 women, [F], mean age 35.8 ± 8.6 years, and a mean body mass index [BMI] of 24.7 ± 3.1) and 40 age-, sex-, and BMI-matched healthy controls (24 M, 16 F, mean age 35.5 ± 8.5 years, and a mean BMI of 24.5 ± 2.8) were included in the study. Patients and controls with a history of any other chronic diseases and obese or underweight subjects were excluded. High-sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and total ghrelin concentrations were studied. Age, sex, BMI, waist circumference, and smoking status were similar between FMF patients and controls (P > 0.05). Adipose tissue-derived molecules including leptin, and adiponectin were lower than healthy controls but only adiponectin levels reached the statistically significance (16.7 ± 8.9 ng/ml vs. 27.7 ± 15.9 ng/ml, P < 0.001) and leptin concentrations just missed significance (25.2 ± 16.2 ng/ml vs. 34.9 ± 27.2 ng/ml, P = 0.051). Ghrelin concentrations were not different between the groups. Adiponectin levels were significantly and negatively correlated with hs-CRP (P < 0.05, r = -0.24). The results of this study suggest that low-grade chronic inflammation during attack-free period in FMF patients may suppress adiponectin production or low levels of adiponectin might contribute to subclinical inflammation in these patients.     

Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes – Results from the EPICOM study

Aims/HypothesisTo investigate long-term consequences of diabetes during pregnancy, we determined adiponectin and leptin levels in adolescents born by women with type 1 diabetic (T1D) or non-diabetic mothers, and determined associations between adiponectin and leptin levels in adolescence and the magnitude of intrauterine hyperglycemia.Research design and methodsWe measured serum adiponectin and leptin and calculated leptin to adiponectin ratio (LAR) in 271 offspring of T1D women (index offspring) (13–20 years), and 297 matched control offspring. Anthropometry included total body fat (TBF) by dual-energy X-ray absorptiometry and an oral glucose tolerance test.ResultsAdiponectin levels were lower in index females (− 8.0% (95% CI; − 13.9, − 1.6)), but not in index males (0.4% (95% CI; − 7.3, 8.6)). Leptin levels were approximately 30% higher in index than control offspring, irrespective of gender. In males, this was seen despite similar TBF in index and control offspring. LAR was increased in index offspring (both males and females) compared with control offspring. There were no association between offspring adiponectin and maternal HbA1c levels in pregnancy. Leptin and LAR seemed to be associated with third trimester HbA1c levels in females in unadjusted, but not adjusted analyses.ConclusionMale and female offspring of women with T1D demonstrated increased serum leptin and LAR, whereas serum adiponectin was reduced in females only. These results suggest that abnormal regulation of adipokines is a consequence of being born to mothers with T1D. No direct association between maternal glycemic control and adiponectin and leptin levels or LAR in the adolescence was found.Clinical Trial Registration number: NCT01559181     

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy

OBJECTIVE: To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Study design: Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. RESULTS: BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. CONCLUSIONS: These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.     

Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents

OBJECTIVES: Adiponectin has been implicated in the pathophysiology of metabolic syndrome and coronary artery disease in humans. Whether adiponectin is related to bone mineralization remains unclear in adults as well as in adolescents. In this study, we aimed to determine the relationship between plasma adiponectin, leptin concentrations and bone density, including total-body bone mineral density (BMD) and bone mineral content (BMC) in adolescence. PATIENTS AND MEASUREMENTS: We studied 105 nondiabetic female adolescents [mean age 15.4 +/- 1.9 years, and mean body mass index (BMI), 23.1 +/- 4.0 kg/m(2)]. A venous blood sample was taken after 12 h of fasting to measure fasting plasma adiponectin and leptin levels. BMD and BMC of the whole body were measured by dual-energy X-ray absorptiometry. RESULTS: In simple correlation analysis, plasma adiponectin and leptin levels correlated significantly with total-body BMD (r =-0.523 and r = 0.443, P < 0.001, respectively) and BMC (r =-0.471 and r = 0.396, P < 0.001, respectively). However, plasma adiponectin and leptin were related to both BMD and BMC in opposite directions. In multivariate linear regression analyses, only BMI or fat mass (FM) and Tanner stage, but not plasma adiponectin and leptin, were significantly related to BMD and BMC following adjustment for other variables. CONCLUSIONS: The results suggest that plasma adiponectin and leptin concentrations are not related to the total-body BMD and BMC independent of the chronological age, BMI or FM, and Tanner stage in nondiabetic female adolescents, although they were highly correlated in simple correlation analyses. The biologic roles of adiponectin in bone still need further clarification.