Serum concentrations of adiponectin and resistin in hyperthyroid Graves' disease patients

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). CONCLUSIONS: Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.     

Perturbations in adiponectin,leptin and resistin levels in acromegaly: lack of correlation with insulin resistance

BACKGROUND: Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear. DESIGN: We investigated the levels of the adipocytokines, resistin, adiponectin and leptin in a group of 18 acromegalic subjects and 18 control subjects matched for age, gender and body mass index. RESULTS: Here we demonstrate for the first time significant elevation in adiponectin levels in acromegalic subjects compared to control subjects 12.5 +/- 1.2 vs. 8.97 +/- 1.1 mg/l, P = 0.029. The resistin levels were similar in acromegalic subjects and controls; 20.65 +/- 2.99 vs. 19.03 +/- 4.72 micro g/l. No evidence of a correlation between adiponectin and insulin resistance as calculated from HOMA-R was found. No correlation was observed either between adiponectin or resistin levels and GH levels, total IGF-I or free IGF-I levels. Leptin levels were significantly reduced in acromegalic subjects, 8.22 +/- 2.26 vs. 18.3 +/- 4.1 micro g/l, P = 0.004. In control subjects, significant correlations between leptin levels and HOMA-R and between resistin levels and HOMA-R were observed. These relationships were not apparent in acromegalic subjects. CONCLUSION: From these data we conclude that changes in resistin and adiponectin levels are unlikely to account for the insulin resistance of acromegaly.     

Association of hyperthyroidism with serum leptin levels

The present study was undertaken to determine whether thyroid hormones affect serum leptin levels in patients with hyperthyroidism. In 32 female patients with hyperthyroidism and 30 body mass index (BMI)-matched control subjects, there was no difference in serum leptin concentrations (9.0+/-1.0 v 8.2+/-0.9 microg/L). The serum leptin levels were compared with the expected values for serum leptin derived from the corresponding BMI with the formula for the control subjects (serum leptin [micrograms per liter] = 0.976 x BMI [kilograms per square meter] - 11.933, P < .001) and are expressed as the percent deviation (%leptin). There was a weak but significant positive correlation between serum free thyroxine (T4) levels and %leptin in the combined analysis of patients with hyperthyroidism and control subjects (r = .28, P < .05). Multiple regression analysis also revealed the independent contribution of free T4 levels to serum leptin. Antithyroid therapy ameliorated the hyperthyroidism and increased the BMI by 7.8% and the percent body fat by 9.9% in a subgroup of 21 patients with hyperthyroidism. However, serum leptin levels did not change during the 2-month therapeutic period (from 9.8+/-1.4 to 8.7+/-1.0 microg/L), and accordingly, %leptin significantly decreased from 133%+/-16% to 98%+/-11% (P < .05). A total of 6 months of observation in 12 hyperthyroid patients showed the same alterations in the anthropometric indexes, serum leptin, and %leptin. These results indicate that serum leptin is slightly increased in subjects with moderate hyperthyroidism, possibly due to the direct action of thyroid hormone, and the levels decline in accordance with the attainment of euthyroidism.     

慢性阻塞性肺疾病患者血清抵抗素和瘦素水平及其与营养状况的关系

目的探讨慢性阻塞性肺疾病(COPD)患者血清抵抗素、瘦素水平及其与营养状况的关系。方法用酶联免疫吸附测定(ELISA)和放射免疫法检测57例稳定期COPD患者和31名健康对照者血清抵抗素、瘦素水平,分析相关因素。结果COPD患者血清抵抗素、瘦素水平[(2·1±1·2)、(0·65±0·41)μg/L]与对照组[(3·6±2·3)、(1·03±0·71)μg/L]比较差异均有统计学意义(P均<0·01)。COPD营养不良患者抵抗素、瘦素水平[(1·7±0·7)、(0·43±0·16)μg/L]显著低于非营养不良患者[(2·2±1·2)、(0·73±0·48)μg/L,P均<0·05]。COPD患者抵抗素与瘦素、第一秒用力呼气容积(FEV1)及FEV1/用力肺活量(FVC)显著正相关(r=0.426~0.531,P均<0·01),瘦素与体重指数(BMI)、胸围、腹围、抵抗素及FEV1/FVC显著正相关(r=0.371~0.580,P均<0·01)。结论COPD稳定期患者血清抵抗素、瘦素水平下降,合并营养不良时下降更显著。     

Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor,free leptin index,adiponectin, and resistin concentrations in healthy humans

The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum adiponectin or resistin concentrations and total energy or macronutrient intake. Thus, total energy intake and macronutrient composition of the diet are associated with sOB-R and free leptin index but do not play a role of comparable significance in predicting adiponectin and resistin concentrations in healthy young subjects.     

Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease

BACKGROUND: There is evidence that adipocytokines play an important role in metabolism and in inflammation. Because human metabolism dramatically changes in inflammatory bowel disease (IBD) and chronic inflammation is the hallmark of the disease, we studied serum levels of leptin, adiponectin, resistin, and ghrelin in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison with healthy controls (HC). METHODS: Leptin, adiponectin, resistin, and active ghrelin serum levels were measured in 100 IBD patients (46 UC and 54 CD) and in 60 matched HC using commercially available enzyme-linked immunosorbent assays. Leptin, adiponectin, resistin, and ghrelin levels were correlated with disease activity, type, localization, and treatment. RESULTS: Mean serum leptin levels were 10.6+/-2.0 ng/mL in UC patients, 12.5+/-2.6 ng/mL in CD patients, and 15.0+/-1.8 ng/mL in HC (P=.01). Mean serum adiponectin levels were 9514.8+/-787.8 ng/mL in UC patients, 7651.1+/-613 ng/mL in CD patients, and 7270.6+/-559.4 ng/mL in HC (P=.05). Mean serum resistin levels were 21.2+/-2.2 ng/mL in UC patients, 18.7+/-1.6 ng/mL in CD patients and 11.8+/-0.6 ng/mL in HC (P=.0002). Mean serum ghrelin levels were 48.2+/-4.2 pg/mL in UC patients, 49.4+/-4.6 pg/mL in CD patients and 14.8+/-3.0 pg/mL in HC (P<.0001). Serum levels of these adipocytokines were not correlated with either C-reactive protein levels or the clinical indices of activity. No association between serum adipocytokines levels and disease localization in both UC and CD patients was found. Only serum ghrelin was significantly higher in ileal compared with colonic CD (P=.04). CONCLUSIONS: Serum levels of adiponectin, resistin, and active ghrelin are increased whereas serum levels of leptin are decreased in patients with IBD. Further studies are needed to elucidate the role of adipocytokines in IBD.     

Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.     

Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-alpha therapy.

AIMS: The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. METHODS: Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. RESULTS: The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. CONCLUSIONS: IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.     

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--insulin and resistin plasma levels in young healthy offspring of patients with essential hypertension

BACKGROUND: Accumulating epidemiological studies have shown that healthy offspring of hypertensive patients exhibit some metabolic disturbances such as hyperinsulinemia, insulin resistance, lipid disorders, elevated plasma leptin levels and reduced insulin receptor number, features that may be predictors of future cardiovascular events. The aim of this study was to determine insulin, adiponectin and resistin plasma levels in young healthy offspring of patients with essential hypertension, and to compare the findings to those of young healthy offspring of healthy normotensives matched for age, sex and body mass index (BMI). METHODS: Forty-six (24 male/22 female) healthy offspring of patients with essential hypertension-positive family history (FH+), mean age 18+/-3 years and BMI 22.4+/-1.4 kg/m2 (group A) and 50 (28 male/22 female) healthy offspring of healthy normotensives-negative family history (FH-) mean age 18+/-3.2 years and BMI 22.6+/-1.7 kg/m2 (group B) were studied. The two groups were matched for age, sex and BMI. Systolic and diastolic blood pressure (SBP and DBP) measurements, resting heart rate (HR), plasma insulin (RIA method), adiponectin and resistin plasma levels (ELISA) were determined in the whole study population. RESULTS: Mean SBP, DBP and resting HR were significantly higher in group A compared with group B (121+/-13 vs 110+/-10 mmHg, 78+/-6 vs 73+/-8 mmHg, 76+/-4 vs 72+/-6 beats/min, p<0.01, p<0.05 and p<0.01 respectively). Insulin and resistin plasma levels were significantly higher, while adiponectin levels were significantly lower. In group A compared with group B (21+/-7 vs 15+/-6 pIU/ml, 10+/-5 vs 6+/-3 ng/ml, 20+/-5 vs 29+/-8 microg/ml, p<0.01, p<0.01, p<0.01, respectively). CONCLUSION: Our findings suggest that increased SBP, DBP and resting HR as well as increased insulin and resistin plasma levels and decreased adiponectin plasma levels pre-exist in young healthy offspring with positive family history for essential hypertension. Further studies are needed to determine the clinical significance of these observations in attempt to classify these young healthy individuals for future cardiovascular risk.     

Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome

BACKGROUND: Cushing's syndrome (CS) is associated with central adiposity, insulin resistance and impaired glucose homeostasis. Adipose tissue is thought to regulates glucose homeostasis via circulating adipokines, such as resistin, leptin and adiponectin, although their role in the insulin resistance associated with CS has not been established. DESIGN: We examined the relationship between insulin resistance and adipokine levels in CS patients. We compared plasma levels of resistin, leptin and adiponectin in 10 women and four men patients with CS, with 14 health subjects matched for age, gender and body mass index. A subgroup of three women and four men with pituitary-dependent CS were re-examined at least 9 months after curative surgery. RESULTS: CS patients had significantly more truncal fat and less lean body mass as assessed by DEXA compared to control subjects. Total cholesterol, triglycerides and insulin resistance, as calculated using the homeostasis model assessment of insulin resistance (HOMA-R), was significantly increased in CS patients. Of the adipokines measured, only resistin was significantly different between female CS patients and female control subjects (5.05 +/- 0.56 vs. 2.91 +/- 0.39 micro g/l, P = 0.015). Curative surgery significantly reduced total body fat and truncal fat, leptin, total and low-density lipoprotein (LDL) cholesterol, glucose and HOMA-R. A reduction in both resistin and adiponectin was also observed but the differences between pre- and post-treatment levels did not achieve statistical significance. CONCLUSION: Here we report for the first time that resistin levels are significantly elevated in CS patients and may be important in the insulin resistance associated with glucocorticoid excess.     

The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus

Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 microg/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.     

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.     

Increase in adiponectin levels during pioglitazone therapy in relation to glucose control, insulin resistance as well as ghrelin and resistin levels

Glitazones increase the secretion of the adipocyte-derived hormone adiponectin. Furthermore, the gastric signal peptide ghrelin is known to suppress adiponectin expression in adipocyte cell culture models. It is not known whether the increase in adiponectin during glitazone therapy is due to a suppression of ghrelin levels, a decrease of resistin concentrations or an amelioration of glucose control. In 10 patients (age 71+/-9 yr, body mass index 29.9+/-3.6 kg/m(2), HbA1c 6.9+/-0.5%) with Type 2 diabetes, who had already been treated with sulfonylureas, we additionally initiated a pioglitazone therapy (30 mg/day) for 12 weeks. To investigate the pioglitazone effect independently of blood glucose, glycosylated hemoglobin (HbA1c) was kept unchanged by reducing the daily dose of sulfonylurea if necessary. Ghrelin concentration [radioimmunoassay (RIA), Phoenix Pharmaceuticals, Mountain View, CA, USA], adiponectin levels [enzyme-linked immunosorbent assay (ELISA), Biovendor, Heidelberg, Germany] as well as resistin concentrations (ELISA, Linco Research, St. Charles, MO, USA) were measured before and after pioglitazone. Glucose control remained unchanged within the 12-week pioglitazone therapy (HbA1c 6.9+/-0.5% before vs 6.8+/-0.6% after pioglitazone) while body weight increased from 86.6+/-9.2 to 88.0+/-9.4 kg (p<0.05), and insulin concentration decreased from 19.6+/-5.7 to 10.1+/-1.6 microU/ml (p<0.05). Adiponectin concentration increased in all patients from 7.70+/-2.47 to 23.33+/-8.28 microg/ml (p<0.01), while resistin concentrations tended to decrease (by 15%; p=0.059). However, ghrelin remained unchanged during therapy. No correlations were observed either between ghrelin, resistin, insulin and adiponectin, or between body weight and hormone plasma levels. The increase in adiponectin levels during pioglitazone therapy seems to be at least partly independent of blood glucose and insulin concentration as well as of ghrelin levels, and it was not associated with a decrease in resistin concentrations.     

Serum leptin and lipids in patients with thyroid dysfunction.

This work was undertaken to examine the relationship between thyroid hormone and serum leptin concentration. This study included 368 Japanese female subjects (27 were affected with pretreatment hyperthyroidism, 68 with hyperthyroidism during treatment, 19 with pretreatment hypothyroidism, 57 with hypothyroidism during treatment and 197 euthyroid control subjects) and 60 control male subjects. In the control group, serum leptin levels in males were lower than those recorded in females (mean +/- SD; 4.6 +/- 4.1 vs 9.5 +/- 6.4 ng/ml, p < 0.001). The leptin values correlated well with body mass index (BMI) and body fat mass (BFM) in both control male and female subjects (p < 0.001 for each). The serum leptin levels in pretreatment female patients with hyperthyroidism were significantly lower than those in the pretreatment patients with primary hypothyroidism and control female subjects (6.4 +/- 3.0 vs 9.7 +/- 6.3, 9.5 +/- 6.4 ng/ml; p < 0.05, 0.02, respectively), but after adjusting for BMI and BFM, the difference was mainly due to the significantly different BMI and BFM. Furthermore, serum leptin did not change significantly during the treatment in hyper and hypothyroidism. There was no correlation between serum leptin and thyroid hormones or lipids levels in female patients with thyroid disorders. Adiposity and gender were the major determinants of leptin concentration, but thyroid hormones did not appear to play any relevant role in leptin synthesis and secretion in human.     

The effect of infliximab on circulating levels of leptin, adiponectin and resistin in patients with inflammatory bowel disease

BACKGROUND: Tumour necrosis factor alpha is a critical mediator of inflammation-related altered metabolism in inflammatory bowel disease (IBD), possibly through its interaction with adipokines, which play an important role in IBD. Infliximab is a well established antitumour necrosis factor alpha treatment in IBD. AIM AND METHODS: We studied serum levels of leptin, adiponectin and resistin in 20 IBD patients before and after infliximab treatment using commercially available enzyme-linked immunosorbent assays. The results were correlated with alterations of disease activity, BMI and C-reactive protein. RESULTS: Infliximab induced clinical response or remission in 18 out of 20 treated IBD patients. Mean serum-leptin levels were 4.6+/-0.5 and 5.1+/-0.5 ng/ml (P=0.41), mean serum-adiponectin levels were 10513.9+/-1216.9 and 9653.5+/-1031.5 ng/ml (P=0.36) and mean serum-resistin levels were 26.3+/-4.1 and 13.9+/-1.4 ng/ml (P=0.004), before and after infliximab treatment, respectively. No significant correlation between the changes of BMI, C-reactive protein or the clinical indices of activity and alterations of the examined adipokines was found. CONCLUSIONS: Serum levels of leptin and adiponectin had no significant alterations, whereas serum-resistin levels are significantly decreased after infliximab therapy in IBD patients, suggesting a possible proinflammatory status for resistin in IBD and a role as a marker of successful therapy.     

Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy

OBJECTIVE: Adiponectin is an adipocyte-specific secretory protein which exhibits antiatherogenic, anti-inflammatory and antidiabetic properties. We hypothesized that testosterone plays an important role in the regulation of its secretion in humans, as adiponectin concentrations are higher in women than in men and as testosterone administration is accompanied by a reduction in serum adiponectin in animals and by reduced protein secretion in cultured adipocytes. This study aimed to evaluate adiponectin levels in hypogonadal men prior to and during testosterone replacement therapy. SUBJECTS AND METHODS: In a retrospective study, adiponectin, total and free testosterone, oestradiol, SHBG, total cholesterol and triglyceride levels were evaluated in 31 hypogonadal men [HM; age, mean +/- SEM: 36.5 +/- 2.4 years; body mass index (BMI) 24.6 +/- 0.8 kg/m2] and 29 weight-matched eugonadal men (EM; age 30.8 +/- 1.5 years; BMI 23.4 +/- 0.6 kg/m2). In 13 HM (age 33.9 +/- 3.2 years; BMI 24.2 +/- 0.9 kg/m2) the same parameters were also evaluated after 6 months of testosterone replacement therapy. Correlation analysis between adiponectin and hormonal, biochemical and anthropometric parameters was performed in all subjects. RESULTS: Testosterone, free testosterone and oestradiol concentrations were significantly lower in HM than in EM (4.4 +/- 0.4 nmol/l, 78.4 +/- 10.9 pmol/l and 36.1 +/- 3.0 pmol/l, respectively, in HM vs. 21.9 +/- 0.7 nmol/l, 507.9 +/- 13.8 pmol/l and 65.2 +/- 1.8 pmol/l, respectively, in EM, P < 0.0001), while SHBG levels in HM were higher than in EM (54.4 +/- 7.5 vs. 30.9 +/- 2.2 nmol/l, P < 0.005). Serum adiponectin levels in HM were significantly higher than in EM (9.53 +/- 0.73 vs. 6.80 +/- 0.55 microg/ml, P < 0.01). Calculation of the Pearson coefficient showed that adiponectin levels in HM were not correlated with any of the anthropometric and hormonal parameters examined, but showed a significant negative correlation with serum triglycerides (r = -0.38, P < 0.05). Serum adiponectin levels were negatively correlated with body weight (r = -0.41, P < 0.05) in EM but not with other anthropometric, hormonal or biochemical parameters. Six months after initiation of testosterone replacement therapy, which increased testosterone and free testosterone levels to the normal range, adiponectin levels were significantly reduced in HM (6.37 +/- 0.93 vs. 9.26 +/- 1.01 microg/ml, P < 0.01) and similar to those recorded in EM. CONCLUSIONS: Compared to eugonadal subjects, hypogonadal men show higher adiponectin levels which are reduced by testosterone replacement therapy. This study indicates that testosterone exerts a regulatory role on adiponectin secretion in humans.     

Serum levels of leptin and changes during the course of recovery from diabetic ketoacidosis

Secretion of leptin, the obese gene product, is stimulated by insulin and glucocorticoids and reduced by fasting. In subjects with diabetic ketoacidosis (DKA), severe insulinopenia and prolonged fasting might cause a decrease in serum leptin levels, and subsequent insulin therapy would reverse the decrease. Otherwise, some other confounding factors, neither insulin nor fasting, might affect serum leptin levels in patients with DKA. The present study was undertaken to address these issues. Eleven patients with type 1 diabetes mellitus (seven males and four females, aged 44+/-6 years, mean +/- SEM), admitted to Jichi Medical School Hospital presenting DKA, were studied during the therapeutic period. Thirty-five sex-, age- and body mass index-matched healthy subjects served as controls. Serum leptin levels at the hospitalization were significantly greater than those of the matched control subjects (5.5+/-1.0 vs. 3.2+/-0.3 microg/l, P < 0.01). After the start of therapy with a small dose of short-acting insulin and a large volume of fluid infusion, serum leptin concentrations further increased to 10.6+/-3.6 microg/l at 24 h, and thereafter the concentrations gradually decreased and normalized at the discharge (3.3+/-0.7 microg/l, day 24+/-4). The peak levels at 24 h were significantly higher than the levels at the discharge (P < 0.05), and also +77+/-34% higher than those at the hospitalization (P < 0.005). Serum cortisol levels (1830+/-200 nmol/l) were markedly elevated at hospitalization. These results indicate that serum leptin levels are increased even under insulinopenia and fasting in the patients with DKA. Such a finding may be associated with marked hyperglycemia or enhanced secretion of glucocorticoid hormone, although the exact mechanisms remain to be elucidated. We speculate that leptin may serve as a stress peptide in DKA, but further analysis is necessary to explore a physiological role of leptin in DKA.     

Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance

CONTEXT: The recently discovered hormone resistin is linked to the development of insulin resistance, but direct evidence of resistin levels in humans with nonalcoholic fatty liver disease (NAFLD) is lacking. METHODS: We conducted this study to assess the relationship between serum resistin and NAFLD. We measured serum resistin and biochemical, hormonal, and histological correlates in 28 NAFLD patients, 33 controls, and 30 obese patients [body mass index (BMI), >30 kg/m2] without NAFLD. RESULTS: Resistin and adiponectin expression were measured in sc adipose tissue by quantitative RT-PCR. Resistin was higher in NAFLD patients compared with controls (5.87 +/- 0.49 vs. 4.30 +/- 0.20 ng/ml; P = 0.002) and obese patients (4.37 +/- 0.27 ng/ml; P = 0.002). Increased resistin mRNA was also found in the adipose tissue of NAFLD patients compared with controls and obese subjects. CONCLUSIONS: Both NAFLD and obese patients had lower adiponectin levels, whereas leptin was increased only in the obese group. No correlation was found between resistin and high-sensitivity C-reactive protein, BMI, homeostasis model assessment, insulin, glucose, transaminases, and lipid values. A positive correlation was found between resistin and histological inflammatory score. These data report increased resistin in NAFLD patients that is related to the histological severity of the disease, but do not support a link between resistin and insulin resistance or BMI in these patients.     

Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal.

OBJECTIVE: Previous studies addressing the influence of thyroid hormones on serum levels of adipokines yielded conflicting results. We aimed to study the impact of short-term overt hypothyroidism on serum leptin, resistin, and adiponectin levels in an in vivo human model. DESIGN: Twenty-two women with differentiated thyroid carcinoma were studied the last day of their thyroxine-suppressive treatment, 4-7 days after withdrawal, and the day before whole-body scanning. Evaluations included serum thyroid hormone, leptin, resistin, and adiponectin concentrations, fasting glucose and insulin, lipid profiles, body temperature, body mass index, and total body fat mass. MAIN OUTCOMES: Thyroid function changed from subclinical or mild hyperthyroidism to normal free thyroxine and triiodothyronine levels, ending in overt hypothyroidism. Thyroxine withdrawal resulted in an increase in serum resistin (p = 0.007) and leptin (p = 0.006) concentrations, whereas adiponectin levels remain unchanged. A significant decrease in body temperature during thyroxine withdrawal was paralleled by a decrease in fasting glucose (p = 0.006) and insulin resistance (p = 0.033), which occurred despite an increase in estimated total body fat mass. CONCLUSION: Thyroid hormones are important regulators of energy balance and intermediate metabolism, influencing the serum concentrations of leptin and resistin.