Decreased plasma adiponectin concentrations in women with low-grade C-reactive protein elevation

OBJECTIVE: Inflammation has been suggested as a risk factor for the development of atherosclerosis, while some components of metabolic syndrome X have been related to inflammatory markers. We hypothesized that adipocyte secreting protein, adiponectin and leptin, for which have been demonstrated an association with metabolic syndrome X and coronary artery disease, may be associated with inflammatory markers in nondiabetic humans. DESIGN AND METHODS: We measured high-sensitivity C-reactive protein (hs-CRP), as an inflammatory marker, and adiponectin and leptin concentrations in 384 nondiabetic Japanese women (mean+/-s.e.m. age 53.6+/-0.8 Years, body mass index (BMI) 23.0+/-0.2 kg/m(2)) undergoing measurement of markers of metabolic syndrome X. RESULTS: The women who had a low-grade hs-CRP elevation (>2.0 mg/l) were significantly older and had higher BMI, body fat mass (BFM), total cholesterol (TC), triglyceride (TG), atherogenic index (AI=(TC-HDLC)/HDLC), where HDLC is high-density lipoproten-cholesterol), fasting blood glucose and leptin concentrations before and after adjustment for BMI or BFM, while lower HDLC and adiponectin concentrations before and after adjustment compared with women with normal CRP levels (<0.5 mg/l). BMI, BFM, TG, AI and leptin before and after adjustment were found to be correlated with hs-CRP levels, while HDLC and adiponectin before and after adjustment were inversely correlated (all P<0.0001). hs-CRP was independently associated with white blood cell count, blood urea nitrogen and AI and inversely with adiponectin/BFM in the stepwise regression analysis model. CONCLUSIONS: These data demonstrate a significant decrease in plasma adiponectin in low-grade chronic inflammation, and suggest that there is an important linkage between inflammation/adipose tIssue/atherosclerosis.     

Decreased plasma concentrations of adiponectin in patients with slow coronary flow

Adiponectin has multiple protective effects on vascular endothelium through anti-inflammatory and anti-atherogenic properties. Recent data suggested that endothelial activation and inflammation may contribute to the pathogenesis of slow coronary flow (SCF). Therefore, we investigated whether adiponectin plasma concentrations were decreased in patients with SCF compared to subjects with normal coronary flow. The study population consisted of 35 patients with angiographically documented SCF in all three coronary arteries and 35 sex- and age-matched cases with normal coronary flow. Coronary flow rates of all participants were determined by Thrombolysis in Myocardial Infarction (TIMI) frame count. Plasma adiponectin concentrations were measured by an enzyme-linked immunosorbent assay method using commercially available adiponectin kits. There were no statistically significant differences between the patients with SCF and the subjects with normal coronary flow in terms of demographic characteristics and cardiovascular risk factors (P > 0.05). Plasma adiponectin concentrations of patients with SCF were found to be significantly lower than those with normal coronary flow (4.77 ± 3.86 mg/ml vs 10.8 ± 6.60 mg/ml, P = 0.001, respectively). Plasma adiponectin levels were correlated significantly and inversely with mean TIMI frame count in patients with SCF (r = −0.441, P = 0.008). Furthermore, the Receiver Operator Characteristics curve of adiponectin concentrations showed that an adiponectin <4.6 mg/ml is associated with SCF with a sensitivity of 68.6%, specificity of 82.9%, positive predictive value of 80.0%, and negative predictive value of 72.5%. Our findings suggest that endothelial inflammation may play a role in the pathogenesis of SCF phenomenon.     

Decreased plasma adiponectin concentrations are closely associated with nonalcoholic hepatic steatosis in obese individuals

OBJECTIVES: To evaluate whether subjects with nonalcoholic hepatic steatosis (HS) differed in their circulating adiponectin levels compared with those in subjects without HS and, if so, to examine to what extent such differences are mediated by the adverse pattern of the metabolic syndrome variables, typically observed in these subjects. DESIGN AND PATIENTS: In a cross-sectional study, we analysed 68 healthy, mildly obese individuals with a negative or negligible daily alcohol consumption. MEASUREMENTS: HS (by ultrasonography), glucose tolerance status (by oral glucose load), insulin resistance [by homeostasis model assessment (HOMA)], and plasma adiponectin concentration [by enzyme-linked immunosorbent assay (ELISA)] were measured. RESULTS: Subjects with nonalcoholic HS (n = 43) had markedly lower plasma adiponectin concentrations than those without HS (n = 25) (5.6 +/- 3 vs. 10.8 +/- 4 microg/ml; P < 0.001). In addition, the former had significantly higher values for body mass index (BMI), waist/hip ratio (WHR), HOMA-insulin resistance score, plasma insulin (at fasting and after glucose load), plasma triglyceride and liver enzyme concentrations [such as alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT)], and tended to have lower high density lipoprotein (HDL) cholesterol concentration. The significant differences in plasma adiponectin levels that were observed between the groups were little affected by adjustment for potential confounding variables, such as age, sex, BMI, WHR, lipids and HOMA-insulin resistance score. Similarly, in multivariate regression analyses, hypoadiponectinaemia significantly predicted the presence of HS (P < 0.001) and the increased levels of GGT and ALT (P < 0.05), independently of potential confounders. CONCLUSIONS: These results show that decreased plasma adiponectin concentrations are closely correlated with nonalcoholic HS in healthy obese individuals.     

Decreased plasma adiponectin concentration in patients with essential hypertension

Adipocytes secrete several biologically active substances that are presumed to be involved in obesity-related hypertension. There are no reports that deal with the relationship between plasma adiponectin concentration and blood pressure (BP).To evaluate the role of adiponectin in essential hypertension 33 patients with essential hypertensive (EHP) (12 women, 21 men) and 33 body mass index-matched normotensive healthy subjects (NHS) (13 women, 20 men) were studied.In EHP plasma adiponectin concentration was significantly lower than in NHS (9.1 +/- 4.5 v 13.7 +/- 5.2 microg/mL, respectively). In all subjects a significant negative correlation was found between plasma adiponectin concentration and mean, systolic, and diastolic BP, suggesting that adiponectin contributes to the clinical course of essential hypertension.     

Decreased plasma adiponectin concentrations are closely related to steatosis in hepatitis C virus-infected patients

OBJECTIVES: The mechanisms underlying steatosis during hepatitis C virus (HCV) infection are complex and multifactorial. Obesity is a well-recognized risk factor for the development of steatosis in chronic hepatitis C infection. The aim of our study was to investigate the role of adipocytokines in HCV-related steatosis. Therefore, we hypothesized that the endocrine function of adipose tissue could be, in part, responsible for HCV-related steatosis. Seventy-one consecutive untreated chronic hepatitis C patients were studied to assess the effects of adipocytokines, body mass index (BMI), age, and HCV genotype on steatosis. We used ELISA to determine serum adiponectin, leptin, and soluble TNF receptors I and II concentrations. RESULTS: Steatosis was observed in 42 (59.1%) patients. BMI was significantly associated with leptin (r = 0.64; P = 0.0001) and was border significantly associated with adiponectin concentrations (r = -0.22; P = 0.06). In univariate analyses, age, HCV genotype 3, BMI, increased leptin level, increased insulin level, and decreased adiponectin concentration were associated with steatosis. In multivariate analysis, steatosis was significantly associated with low adiponectin concentration, age, HCV genotype 3, and aspartate aminotransferase (ASAT) level, whereas steatosis was not associated with leptin, insulin, and BMI. CONCLUSION: In chronic HCV patients, hypoadiponectinemia is significantly associated with the development of liver steatosis. The fact that the plasma levels of adiponectin inversely correlate with steatosis in HCV-infected subjects suggests that hypoadiponectinemia may contribute to hepatic steatosis progression and liver injury in this population. One practical implication is that therapy to increase circulating adiponectin concentration, such as overweight reduction or thiazolidinediones, provides the potential to improve steatosis in chronic hepatitis C infection.     

Paradoxical elevation in adiponectin concentrations in women with preeclampsia

Adiponectin is a recently identified, insulin-sensitizing and anti-inflammatory protein released by adipocytes, which is paradoxically reduced in obesity. It suppresses endothelial activation. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE), together with enhanced inflammatory and endothelial activation. Women with increased body mass index (BMI) and insulin resistance are predisposed to PE. We hypothesized that adiponectin concentrations are reduced in normal pregnancy compared with postpartum values and further reduced in women with PE. Fifteen women with PE and 30 control subjects with similar first trimester BMI had adiponectin concentrations measured in the third trimester; postpartum measurements were repeated in 16 control subjects. Adiponectin concentration in healthy pregnant women correlated inversely with early pregnancy BMI (r=-0.47, P=0.01) and fasting insulin concentrations (r=-0.58, P=0.001). However, adiponectin concentrations did not differ significantly in pregnancy and postpartum samples (mean change, -0.15 microg/mL; 95% CI, -2.28 to 1.98, P=0.88). Plasma adiponectin concentrations were markedly elevated (P=0.01) in women with PE (mean, 21.6; SD, 8.18 microg/mL) compared with control subjects (mean, 14.7; SD, 7.06 microg/mL). Moreover, in PE, adiponectin concentrations did not correlate with first trimester BMI or insulin or with serum urate or creatinine concentrations or urinary protein levels. We conclude that plasma adiponectin concentrations are not elevated in normal human pregnancy and paradoxically elevated (by 47%) in women with PE. This may be secondary to exaggerated nonspecific adipocyte lipolysis or as a physiological response to enhance fat utilization and attenuate endothelial damage. Future studies should determine whether adiponectin concentrations help improve prediction of PE.     

Decreased plasma adiponectin levels in young obese males

Plasma adiponectin levels are reduced in middle-aged obesity and in patients with type 2 diabetes and coronary artery disease. The purpose of this study was to investigate the effects of early-aged obesity on plasma adiponectin level. Twenty-six male college students (19.2 +/- 1.1 years, obese group: n = 15, [body mass index > 25, percent body fat > 25%], non-obese group: n = 11) participated in the present study. We measured anthropometric parameters and plasma adiponectin and leptin level. Plasma adiponectin levels in the obese group were significantly lower than those in the non-obese group (obese: 4.7 +/- 2.0 micro g/ml, non-obese: 6.8 +/- 2.2 micro g/ml, p < 0.05). On the other hand, plasma leptin levels in the obese group were significantly higher than those in the non-obese group (obese: 8.4 +/- 3.2 ng/ml, non-obese: 2.6 +/- 2.1 ng/ml, p < 0.001). Plasma adiponectin levels were significantly correlated with body weight (r = -0.415, p < 0.05) and percent body fat (r = -0.412, p < 0.05). Stepwise multiple regression analysis revealed that percent body fat was a significant independent predictor of plasma adiponectin level (r = 0.406, p < 0.05). These results show that obesity is associated with reduced plasma adiponectin even in young subjects.     

Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels

Abstract: Background: Adiponectin is a hormone secreted by adipocytes and has anti‐diabetic and anti‐atherogenic properties. Hypoadiponectinemia is associated with insulin‐resistant diabetes and liver dysfunction. The aim of this study was to determine plasma adiponectin and insulin levels in patients with liver cirrhosis. Methods: Adiponectin and insulin levels were determined in 38 patients with cirrhosis and 30 healthy controls, and were correlated with various clinical and biochemical parameters. Patients included 21 with Child A, eight Child B, and nine with Child C liver cirrhosis. Results: Log adiponectin and insulin levels were significantly elevated in patients with cirrhosis compared with the control. In liver cirrhosis, the level of adiponectin increased proportionately with the Child's classification score. In control subjects, plasma adiponectin correlated inversely with insulin levels. In contrast, plasma adiponectin correlated positively with insulin levels in patients with liver cirrhosis. Plasma adiponectin levels did not correlate with age, sex, body mass index, total bilirubin, aspartate aminotransferase, and fasting blood sugar levels in both groups, while alanine aminotransferase correlated negatively with adiponectin in control subjects as reported previously. Conclusion: Our results of high plasma adiponectin in patients with liver cirrhosis could reflect an imbalance between its production by adipocytes and metabolism in the liver.     

Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer

AIM:To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced).METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive c...     

Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes

As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM.     

Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high-risk nondiabetic patients

OBJECTIVE: To investigate the association of plasma adiponectin levels with coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based modified Duke Index score) in 400 nondiabetic patients undergoing coronary angiography. HT was diagnosed by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines or if patients were on antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted the coronary atherosclerotic burden independent of other cardiovascular risk factors. However, they were similar in NT and HT and showed no correlation with blood pressure values. In non-CAD, but not in CAD patients, they were lower in patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P = 0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma adiponectin levels are inversely related to CAD severity and IR; however, they are not strongly related to blood pressure values.     

Decrease in plasma adiponectin concentrations in patients with variant angina pectoris.

BACKGROUND: Plasma adiponectin is decreased in patients with coronary artery diseases, especially in patients with acute coronary syndrome (ACS). However, the correlation between plasma adiponectin and variant angina pectoris (VAP) has not been verified. Plasma adiponectin concentrations between VAP and other coronary artery diseases was compared in the present study. The association between plasma adiponectin concentration and VAP was also investigated. METHODS AND RESULTS: Plasma adiponectin concentrations in the VAP group (n=101) were compared with those of the ACS group (n=117), the stable angina pectoris group (n=108), and the normal coronary group (n=81). Plasma adiponectin concentrations in VAP and ACS were significantly lower than that of the normal coronary group (6.6+/-5.4 vs 5.2+/-4.0 vs 9.0 +/-6.2 microg/ml, p<0.001, respectively). Multivariate analysis indicated that plasma adiponectin (odds ratio (OR) 0.735, 95% confidence interval (CI) 0.621-0.855, p=0.011), smoking (OR 2.012, 95% CI 1.210-3.880, p=0.020), and age (OR 0.976, 95% CI 0.957-0.997, p=0.022) correlated independently with the development of VAP. CONCLUSIONS: Our results suggest that a decrease in plasma adiponectin concentration might be associated with the development of VAP.     

Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects

The purpose of this study was to investigate plasma adiponectin concentration and its relation with metabolic parameters in overweight and normal weight subjects. The study was carried out in 46 overweight subjects (20 male, 26 female; mean age 39.4 +/- 10.2 years) and 48 (19 male, 29 female; mean age 36.1 +/- 10.6 years) sex- and age-matched normal weight subjects. Anthropometric measurements were recorded and adiponectin, glucose, insulin, lipid profile, total homocysteine (tHcy) and fibrinogen levels were measured. The insulin resistance index was assessed by homeostasis model assessment for insulin resistance (HOMA-IR). Plasma mean adiponectin concentrations of the overweight subjects were significantly lower than those of normal weight subjects (15.0 +/- 4.2 vs 17.3 +/- 5.6 ng/ml) (P<0.05). In overweight subjects, adiponectin levels negatively correlated with body weight (r = -0.35, P<0.001), body mass index (BMI) (r = -0.28, P<0.006), systolic blood pressure (r = -0.21, P<0.04), fasting insulin (r = -0.19, P<0.01) and HOMA-IR (r = -0.20, P<0.01) and positively with high-density lipoprotein cholesterol (HDL-C) (r = 0.27, P<0.009). Overweight subjects with low HDL-C levels had significantly decreased plasma adiponectin levels compared to those with high HDL-C levels (P<0.05). Multiple regression analysis revealed that BMI, HOMA-IR and HDL-C explained 12%, 20% and 15% variance of the adiponectin concentrations. These findings may suggest that circulating adiponectin is associated with insulin resistance and HDL-C levels independent from BMI in overweight subjects.     

Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR)

Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P < 0.001). The SSPG concentration also correlated to a similar degree (P < 0.001) with FPI (r = 0.60) and HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = ?0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = ?0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40 % of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.     

Usefulness of insulin resistance measured by homeostasis model assessment in predicting restenosis after coronary stent placement in nondiabetic patients

The homeostasis model assessment enabled us to evaluate insulin resistance easily and accurately in the clinical setting. The restenosis rate of coronary stenting was significantly higher among patients with high values for the homeostasis model assessment. Our findings suggest that insulin resistance measured by the homeostasis model assessment predicts restenosis after coronary stent placement in nondiabetic patients.