Effect of experimental hypo- and hyperthyroidism on serum adiponectin

Adiponectin, an adipocyte-derived hormone, has been shown to decrease body weight by increasing thermogenesis and lipid oxidation. Thyroid hormones have similar effects. Here we investigated if experimental hypo- and hyperthyroidism in rats would induce changes in serum adiponectin concentration. Adult rats became hypothyroid by treatment with 0.03% methimazole in the drinking water for 28 days or hyperthyroid by subcutaneous thyroxine injections (50 microg/100g body weight) for 10 days. Serum adiponectin level of hyperthyroid rats was 3.2-fold higher than that of euthyroid ones (P < .001), whereas that in hypothyroid rats tended to be lower (38%), but without statistical significance. Serum adiponectin had a positive correlation with serum thyroxine (r = .81, P < .001) and triiodothyronine (r = 0.68, P = .03) and a negative correlation with serum thyroid-stimulating hormone (P = -.62, r = 0.015). In addition, there was a negative correlation between serum adiponectin level and total visceral white adipose mass (= sum of inguinal, epididymal, and retroperitoneal depots; r = -0.43; P = .032), which was reduced by 40.5% in hyperthyroid (P < .01) but not in hypothyroid animals. A positive association between serum adiponectin level and brown adipose tissue mass was found (r = 0.43, P = .03), but not with body weight, which was reduced in both hypo- and hyperthyroid groups. Adiponectin has been reported to have an insulin-sensitizing effect. However, in hyperthyroid rats, higher serum adiponectin level was not accompanied by statistically different changes in basal serum insulin levels, blood glucose concentrations, or glucose tolerance as compared with euthyroid rats, except for a slight increase in blood glucose level at 120 minutes after glucose intraperitoneal administration (P < .05). Therefore, experimental hypothyroidism did not change serum adiponectin concentration, whereas hyperthyroidism induced an important elevation in the serum hormone concentration, with still unknown biological significance.     

Association of Plasma Adiponectin Concentrations with Chronic Lymphocytic Leukemia and Myeloproliferative Diseases

Adiponectin, an adipocyte-secreted hormone, is an important negative regulator in the immune system and hematopoiesis. In this study, we investigated the association of adiponectin levels with chronic lymphocytic leukemia (CLL) and myeloproliferative diseases (MPDs). We measured adiponectin levels in 19 patients with CLL and 30 patients with MPD (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were (chronic myelogenous leukemia, 15; polycythemia vera, 9; myelofibrosis, 4; essential thrombocythemia, 2). The data were compared with results from a control group of healthy volunteers who were matched according to age, sex, and body mass index. The adiponectin levels in patients with CLL were lower than in the controls (4.71 +/- 1.33 microg/mL versus 16.61 +/- 3.91 microg/mL; P <.001). They were also significantly lower in patients with MPD than in the controls (8.95 +/- 1.33 microg/mL versus 16.16 +/- 4.77 microg/mL; P <.001). In addition, we compared the adiponectin levels of MPD patients who were treated with interferon (IFN) to the levels of patients who were not treated with IFN. Adipnectin levels were significantly higher in IFN-treated patients (11.03 +/- 1.39 microg/mL versus 6.87 +/- 1.79 microg/mL; P <.001). These results suggest that lymphopoiesis and myelopoiesis negatively influence adiponectin levels. Adiponectin may be related to inflammatory cytokine release. IFN therapy appears to have a positive influence on adiponectin secretion by suppressing inflammatory cytokines. Future studies are needed to prove causality and to provide insight about this hormone's mechanism of action and its potential role regarding the etiology and progression of CLL and MPD.     

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.     

Opposite changes in circulating adiponectin in women with bulimia nervosa or binge eating disorder

Adiponectin is a recently discovered peripheral peptide that is secreted exclusively by differentiated adipocytes. It has been shown to enhance insulin sensitivity, control body weight, regulate lipid homeostasis, and prevent atherosclerosis. Dysregulation of both lipid and glucose metabolism and changes in body weight and body fat mass have been reported in bulimia nervosa (BN) and/or binge eating disorder (BED); hence, investigation of adiponectin secretion is of obvious interest in these eating disorders. To this purpose, we measured plasma levels of adiponectin, glucose, cholesterol, triglycerides, and thyroid hormones in 60 drug-free women, including 20 patients with BN, 20 patients with BED, and 20 healthy controls. Compared with healthy women, BN women exhibited significantly increased circulating adiponectin levels (P < 0.002) and cholesterol concentrations (P < 0.005), whereas BED women had significantly reduced plasma levels of adiponectin (P < 0.005) and increased concentrations of glucose (P < 0.01), cholesterol (P < 0.05), and triglycerides (P < 0.02). Moreover, plasma levels of adiponectin were significantly correlated to the frequency of binge/vomiting episodes (r = 0.65, P = 0.002) in bulimics but not to the frequency of bingeing in BED patients. Because we did not include a group of obese patients who did not binge eat, the specificity of our findings in the BED should be considered cautiously. However, on the basis of present results, it is tempting to speculate that the increased production of adiponectin in BN may represent a compensatory mechanism to counteract the possible development of insulin resistance, whereas the decreased secretion of adiponectin in individuals with BED may be a risk factor for the development of glucose intolerance.     

Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

OBJECTIVE: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. DESIGN: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 microg of acitretin. METHODS: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. RESULTS: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 +/- 0.034 versus 0.329 +/- 0.051; P < 0.05) and HOMA-IR index (1.53 +/- 0.73 versus 2.59 +/- 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 +/- 11.7 versus 39.4 +/- 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 +/- 4.4 versus 6.2 +/- 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor alpha (TNFalpha) levels, which persisted elevated throughout the treatment. CONCLUSIONS: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFalpha levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.     

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.     

Adiponectin levels in women with polycystic ovary syndrome

Serum adiponectin levels were evaluated in 60 women with polycystic ovary syndrome (PCOS), 30 normal-weighted and 30 obese women, and 60 healthy women age and body mass index (BMI) matched with the patients. The homeostasis model assessment (HOMA) score was also calculated. Both in PCOS and controls, serum adiponectin levels were significantly (P < 0.05) lower in obese than normal-weight women, without any difference between PCOS and controls. The HOMA score was significantly (P < 0.05) higher in obese than normal-weight women both in PCOS and controls; additionally, the HOMA score was significantly (P < 0.05) higher in normal-weight PCOS than normal-weight controls. Both in PCOS and controls, adiponectin levels were significantly correlated with BMI (r = -0.51, P < 0.01 in PCOS; r = -0.45, P < 0.01 in controls) and HOMA values (r = -0.39, P < 0.05 in PCOS; r = -0.35, P < 0.05 in controls); HOMA was correlated with BMI (r = 0.51, P < 0.01 in PCOS, r = 0.61, P < 0.001 in controls). In conclusion, our results confirm that adiponectin concentrations change according to variations of fat mass. They further suggest that insulin sensitivity per se probably does not play any pivotal role in the control of adiponectin levels in PCOS women.     

Identification of influencing variables on adiponectin serum levels in diabetes mellitus type 1 and type 2.

BACKGROUND: Adiponectin represents an adipocyte-specific secretory protein that has been discussed recently as candidate gene and promising new drug target to restore insulin sensitivity in diabetes mellitus type 2. AIM: The aim of the present study was to define influencing variables on adiponectin serum levels in a large cohort of caucasian patients with type 1/type 2 diabetes and healthy controls. Additionally, adiponectin gene polymorphisms (Tyr111His and Gly15Gly) were investigated for possible associations with adiponectin serum levels. METHODS: Adiponectin serum concentrations were measured in a metabolically well characterized cohort of 892 caucasian patients (556 with type 2 diabetes, 118 with type 1 diabetes, 218 controls) by ELISA. Gene polymorphisms were determined by PCR-based RFLP. RESULTS: 1) Adiponectin values are dependent on gender with higher levels in diabetic females than in diabetic males. This gender-specific effect was only restricted to patients with diabetes and cannot be observed in controls. 2) In contrast to previous studies, the presence of diabetes does not influence adiponectin serum levels after correction for BMI. In addition, age has no influence on adiponectin levels. 3) Adiponectin levels are dependent on renal function at a creatinine clearance < 45 ml/min. 4) Regression analysis showed a significant, but only weak correlation between BMI and adiponectin in patients with diabetes mellitus type 2 (r = 0.47) and type 1 (r = 0.57). 5) Adiponectin gene polymorphisms (Tyr111His and Gly15Gly) do not influence adiponectin levels. CONCLUSIONS: Adiponectin serum concentrations can only be interpreted after careful correction for gender and renal function, whereas the genetic variants Tyr11His and Gly15Gly do not seem to play a role. The correlation between BMI and adiponectin was weaker than expected in diabetic patients.     

Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients

BACKGROUND: Adiponectin is an adipocyte-derived protein with insulin-sensitizing and antiatherogenic properties. Failure to decrease blood pressure (BP) normally during night in hypertensive patients has been independently associated with left ventricular hypertrophy. METHODS: We examined the relationship between adiponectin levels, insulin sensitivity, and left ventricular structure in 40 newly diagnosed never-treated patients with essential hypertension, including 20 patients with a normal night-time pressure decrease (ie, dippers) and 20 patients with BP persistently elevated throughout the 24-h period (ie, nondippers). All subjects had grade 1-2 hypertension, aged 18 to 65 years, no diabetes mellitus, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease. RESULTS: The two groups of patients were similar for age, sex, body mass index, and had no differences for clinic, 24-h, and diurnal BP, and 24-h, diurnal, and nocturnal heart rate, as well as glucose, total cholesterol, and triglyceride levels. Plasma insulin and homeostasis model assessment (HOMA index) were higher (P < .01), and adiponectin levels were lower (P < .005) in nondippers than in dippers. Adiponectin correlated inversely with HOMA index and insulin levels (r = -0.58, and r = -0.62, respectively, P < .001) in the entire population. Nondippers showed left ventricular mass, relative wall thickness, and measure of early and late diastolic peak flow velocity ratio similar to those of dippers. CONCLUSIONS: In the absence of major cardiovascular risk factors, nondipper essential hypertensive patients show more prominent insulin resistance and lower adiponectin compared to dippers. Therapeutic modulation of adiponectin or insulin resistance might provide additional benefit to the conventional antihypertensive treatment.     

Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus

Postprandial hyperglycemia is associated with increased cardiovascular mortality; therefore, lowering postprandial hyperglycemia seems crucial in type 2 diabetes mellitus. We assessed the effect of 2 different postprandial glucose-lowering agents, the alpha-glucosidase inhibitor miglitol and the meglitinide analogue mitiglinide, on metabolic profile and atherosclerosis-related markers. Glucose levels, insulin levels, lipid profile, serum adiponectin, pulse wave velocity (PWV), and urinary albumin excretion rate (AER) were assessed before and after 3 months in 28 patients with type 2 diabetes mellitus randomly allocated to either miglitol 150 mg/d or mitiglinide 30 mg/d. Both agents improved postprandial glucose levels but exhibited different patterns of insulin levels. Body mass index (BMI) tended to decrease with miglitol (P = .06), and homeostasis model assessment of insulin resistance and AER significantly decreased (P < .05 and P < .001, respectively) with miglitol; these changes were not obtained with mitiglinide. Pulse wave velocity did not change. The 3-month changes in 1,5-anhydroglucitol levels were significantly more with miglitol than with mitiglinide (P = .007). Adiponectin levels were significantly increased only with miglitol (P < .01), and the 3-month changes were significantly more with miglitol than with mitiglinide (P = .048). The significant increase in adiponectin by miglitol was inversely correlated with the ratio of the 60-minute change in blood glucose at 3 months divided by the change at baseline (r = -0.59, P = .020), which was independent of the effect of age, sex, changes in hemoglobin A(1c) and BMI, and the baseline concentration of adiponectin. The present comparative study indicated favorable effects of miglitol on BMI, homeostasis model assessment of insulin resistance, adiponectin, and AER, which are markers related to insulin resistance and atherosclerosis. Future studies are needed to elucidate the long-term effect.     

The reciprocal association of adipocytokines with insulin resistance and C-reactive protein in clinically healthy men

In experimental models, adiponectin improves and tumor necrosis factor alpha (TNF- alpha ) impairs insulin action, and the expression of these adipocytokines seems to have a reciprocal regulation. The aim was to examine whether in a cross-sectional study, associations supporting this concept may be found in 58-year-old clinically healthy men, and also the relation to C-reactive protein (CRP). In 102 men, euglycemic hyperinsulinemic clamp was used to assess glucose infusion rate (GIR). Total body fat (dual-energy x-ray absorptiometry), plasma adiponectin (radioimmunoassay), TNF-alpha , and CRP (enzyme-linked immunosorbent assay) were measured. Adiponectin correlated positively to GIR (r=0.33, P<.001) and negatively to total fat mass (r=-0.29, P=.004), whereas TNF- alpha showed reverse associations (r=-0.31, P<.01, and r=0.31, P<.01). Adiponectin and TNF- alpha were negatively correlated (-0.28, P=.006). An interaction term (TNF- alpha /adiponectin ratio) and body fat together explained 31.3% (P<.001) in GIR variability. The odds ratio for having insulin resistance was 9.3 (95% CI, 2.2-38.9) in subjects with TNF-alpha values above and adiponectin levels below the median, as compared to subjects with TNF- alpha values below and adiponectin levels above the median. Total fat and TNF-alpha , but not adiponectin, were significantly associated with log CRP (R2=20%, P<.001). In conclusion, this study in man showed that plasma adiponectin and TNF-alpha were independently and reversely associated with insulin resistance. C-reactive protein levels were related to TNF-alpha and obesity.     

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis

RATIONALE: Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. AIM: To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). METHODS: Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. RESULTS: CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CONCLUSION: CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.     

Serum adiponectin level as an independent predictor of mortality in patients with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is associated with altered energy homeostasis and myocardial inflammation, hypertrophy, and fibrosis. Adiponectin, an insulin-sensitizing adipocytokine, may affect these pathogenic factors, and the circulating adiponectin level may serve as a biological marker of CHF. This study aimed to assess the significance of serum adiponectin as a prognostic marker for Japanese CHF patients. METHODS AND RESULTS: The serum adiponectin levels were compared between 54 (24 ischemic and 30 non-ischemic) CHF patients with left ventricular systolic dysfunction and 55 age- and gender-matched control subjects. The CHF patients also underwent simultaneous clinical assessment and measurements for brain natriuretic peptide (BNP) and parameters of lipid or glucose metabolism. Compared with the controls, the CHF patients showed significantly increased serum adiponectin levels [6.7 (4.9-12.6) vs 14.6 (9.7-25.4) microg/ml, p<0.0001]. In the CHF patients, the log-transformed values of the serum adiponectin levels positively correlated with the log-transformed values of the plasma BNP levels (p=0.0003, r=0.48) and inversely correlated with the body mass index (p=0.0006, r=-0.46). Furthermore, an increase in the serum adiponectin level was associated with higher mortality (p<0.05), particularly in the ischemic CHF patients (p<0.005). CONCLUSIONS: An increase in the circulating adiponectin level was associated with higher mortality in the ischemic CHF patients. Adiponectin may be an informative risk marker for Japanese CHF patients.     

Evaluation of serum adiponectin levels in diabetic nephropathy

IntroductionDiabetic nephropathy is one of the major microvascular complications of diabetes mellitus. Adiponectin is an adipose tissue-derived cytokine that was identified in a human adipose tissue cDNA library. Serum adiponectin levels are found to be reduced in various pathological states including obesity, diabetes mellitus, ischaemic heart disease and arteriosclerosis obliterans and elevated in end stage renal diseases. Objective: to assess the level of plasma adiponectin as an early predictor of microvascular complications in patients with type 2 diabetes mellitus.Methods44 patients with type 2 diabetes recruited from outpatient diabetes clinic in Kasr Alainy hospital. All patients were subjected to full laboratory work-up including: Fasting blood glucose and Post prandial blood glucose, Glycated haemoglobin A1C, Serum creatinine, Serum total cholesterol, Triglycerides, Low density lipoprotein, High density lipoprotein, C-reactive protein titre, serum adiponectin and Urinary albumin/creatinine (UAC) ratio.ResultsThe present study demonstrated that serum adiponectin concentrations had significant positive correlation with UAC ratio (r = 0.534, p = 0.0001). Adiponectin levels showed significant positive correlation in patients with diabetes and hypertension with microalbumiuria (p = .001) or normoalbumiuria (p = 0.004).ConclusionSerum adiponectin level can be a good predictor of diabetic nephropathy in patients with type 2 diabetes mellitus.     

Relationships between plasma adiponectin and body fat distribution, insulin sensitivity, and plasma lipoproteins in Alaskan Yup'ik Eskimos: the Center for Alaska Native Health Research study

Adiponectin, a protein secreted by adipose tissue, has antiatherogenic, anti-inflammatory, and insulin-sensitizing actions. We examined the relationship between plasma adiponectin and adiposity, insulin resistance, plasma lipids, glucose, leptin, and anthropometric measurements in 316 adult men and 353 adult women Yup'ik Eskimos in Southwest Alaska. Adiponectin concentration was negatively associated with body mass index, percentage of body fat, sum of skin folds, waist circumference, triglycerides, insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]), fasting insulin, and leptin in both men and women, and also with glucose in women. Adiponectin concentration correlated positively with high-density lipoprotein cholesterol concentration, and also with low-density lipoprotein cholesterol in women. Insulin-sensitive individuals (HOMA-IR <3.52, n = 442) had higher plasma adiponectin concentrations than more insulin-resistant individuals (HOMA-IR ≥3.52, n = 224): 11.02 ± 0.27 μg/mL vs 8.26 ± 0.32 μg/mL, P < .001. Adiponectin concentrations did not differ between groups of participants with low and high level of risk for developing coronary heart disease. No difference in plasma adiponectin levels was found among Yup'ik Eskimos and whites matched for sex, age, and body mass index. In conclusion, circulating adiponectin concentrations were most strongly associated with sum of skin folds in Yup'ik men and with high-density lipoprotein cholesterol levels, sum of skin folds, waist circumference, and insulin and triglycerides concentrations in Yup'ik women.     

Adiponectin levels in prepubertal children with Prader-Willi syndrome before and during growth hormone therapy

CONTEXT: Children with Prader-Willi syndrome (PWS) may have obesity and an abnormal body composition with a high body fat percentage, even if they have a normal body weight. Adiponectin has been inversely related to obesity and insulin resistance. OBJECTIVE: The objective of the study was to evaluate in prepubertal PWS children the following: 1) adiponectin levels, body composition, carbohydrate metabolism, and triglyceride levels; 2) associations between adiponectin and body composition, carbohydrate metabolism, and triglycerides; and 3) effects of GH treatment on these outcome measures. PATIENTS: Twenty prepubertal PWS children participated in the study. INTERVENTION: The subjects were randomized into a GH treatment group (n=10, 1 mg/m2.d) and a non-GH-treated control group (n=10). MAIN OUTCOME MEASURES: At baseline, after 1 and 2 yr of GH treatment, fasting levels of adiponectin, glucose, insulin, and triglycerides were assessed. Body composition and fat distribution were measured by dual energy x-ray absorptiometry. RESULTS: PWS children had significantly higher median (interquartile range) adiponectin levels [17.1 mg/liter (13.9-23.2)] than healthy sex- and age-matched controls [11.8 mg/liter (9.7-12.5), P<0.005]. Body fat percentage was significantly higher than 0 sd score [1.8 sd score (1.5-2.1), P<0.001]. Adiponectin levels were inversely related to triglyceride levels (r=-0.52, P=0.03). There was a tendency to an inverse relation with body fat percentage and body mass index, but no correlation with fasting insulin or glucose levels, the insulin to glucose ratio, or homeostasis model assessment index. During GH treatment, adiponectin levels increased significantly and did not change in randomized controls. CONCLUSION: Adiponectin levels were increased, and inversely associated with triglyceride levels, in prepubertal, not overweight PWS children, although they had a relatively high body fat percentage. During GH treatment, adiponectin levels further increased, whereas no change was found in the controls, which is reassuring with respect to the development of insulin resistance during GH treatment.     

Adiponectin is independently associated with glycosylated haemoglobin

BACKGROUND: In humans, adiponectin has been demonstrated to circulate in inverse proportion to the degree of insulin resistance. OBJECTIVE: To investigate the association between adiponectin and glycosylated haemoglobin (HbA1c) in a population-based study. DESIGN AND METHODS: Two hundred and ninety-seven individuals aged 30-75 years were enrolled in a cross-sectional study. They included patients with type 2 (non-insulin-dependent) diabetes mellitus and stable, good metabolic control (n=32) and individuals with glucose intolerance (n=54). Adiponectin was measured using a sandwich enzyme-linked immunosorbent assay (intra-assay and interassay coefficients of variation 3.3 and 7.4% respectively). RESULTS: Adiponectin correlated with age (r=0.161; P=0.006), body mass index (r=-0.197; P=0.001), diastolic blood pressure (r=-0.181; P=0.005), fasting glucose and HbA1c (r=-0.251 and r=-0.22 respectively; P<0.0001), high-density lipoprotein cholesterol (r=0.442; P<0.001) and serum triglycerides (r=-362; P<0.001). In multiple regression analysis, sex, age, fasting and post-load glucose, and adiponectin independently contributed to 40% of the variance in HbA1c. Among individuals with normal glucose tolerance, fasting glucose (P=0.0033), post-load glucose (P=0.0015), age (P=0.001) and adiponectin (P=0.0083) independently contributed to 21% of the variance in HbA1c. CONCLUSION: Adiponectin is significantly associated with altered glucose metabolism and independently contributes to the variance of HbA1c in a population-based manner.     

Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis

CONTEXT: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein. OBJECTIVE: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control. METHODS: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8). Overnight fasting sera were analyzed for free and total IGF-I and IGF-binding proteins. Glucose regulatory hormones were examined after an oral glucose tolerance test and GH after stimulation with GHRH. RESULTS: Systemic drainage led to higher basal and stimulated insulin levels than portal drainage (P < 0.05), but increments in response to oral glucose were reduced in both transplanted groups (P < 0.05 vs. controls). However, glucose tolerance was similar in all groups. Circulating free and total IGF-I and IGF-binding protein-3 were similar to control levels in the systemic drainage group but elevated in the portal drainage group (P < 0.05). Consistently, the GH response was reduced in the portal drainage group (P < 0.05 vs. controls) and correlated inversely with free IGF-I (r = -0.63, P < 0.05). CONCLUSION: Portal drainage of pancreatic endocrine secretion in pancreas graft recipients raises IGF-I and lowers GH secretion. These changes might explain that glucose regulation is maintained despite lower peripheral insulin levels, compared with patients with systemic graft drainage and nondiabetic control subjects.     

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.     

The association between insulin resistance and cytokines in adolescents: the role of weight status and exercise

Increased adiposity is associated with insulin resistance (IR) and an inflammatory response in adults. We tested the hypotheses that cytokines associated with adiposity are also correlated with IR in early adolescents and that these relationships are moderated by weight status, levels of vigorous physical activity (VPA), or maximal aerobic power (pVO2max). Body mass, stature, and a fasting blood sample were obtained from 120 midpubertal adolescents (60 girls and 60 boys). Habitual VPA was obtained by a survey. Predicted VO2max was determined using a cycle ergometer test. Weight status was based on body mass index (BMI) percentiles (normal weight=BMI<75th percentile, overweight=BMI>95th percentile). Glucose, insulin, adiponectin, resistin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 were measured; and IR index was based on the Homeostatic Model Assessment. Adiponectin, resistin, and TNF-alpha were associated with IR in all adolescents (R2=0.329, P<.001; R2=0.152, P=.001; and R2=0.141, P=.002; respectively); but interleukin-6 was not (R2=0.148, P=.114). The degree of association between adiponectin and IR was stronger in overweight than in normal-weight adolescents (P<.050). When regression models included weight status, neither TNF-alpha nor resistin was significantly related to IR (P>.050). Exercise did not moderate the association between these cytokines and IR. However, higher levels of VPA and/or pVO2max were associated with higher adiponectin, lower resistin, and lower TNF-alpha in at least one of the sexes. Our results indicate that the pathophysiology of obesity is already established in early adolescents. Increased adiposity, resulting in reduced adiponectin and increased resistin and TNF-alpha, may link these cytokines with IR in adolescents.