Association Of Plasma Adiponectin Research Articles

Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer.

BackgroundAdipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival.MethodsPlasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided.ResultsWe found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m2) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS.ConclusionsLower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.

Plasma Adiponectin and Blood Pressure Progression in African Americans: The Jackson Heart Study.

Little is known on the association of plasma adiponectin with blood pressure (BP) changes in African Americans (AAs). We evaluated the associations between plasma adiponectin and BP progression among AAs. We analyzed data from 1,184 participants without hypertension at baseline (2000-2004) with ≥1 follow-up visits in the Jackson Heart Study. We used robust Poisson regression to generate risk ratios (RRs) for BP progression (an increase by ≥1 BP stage) and incident hypertension. Over a median of 7 years, 71% progressed to higher BP stage and 65% developed hypertension. We found evidence of interaction by sex (P-interaction = 0.088). Compared with those in the lowest quartile (Q1), male participants in the highest adiponectin quartile (Q4) had reduced risks of BP progression (RR 0.76 [95% confidence interval, CI, 0.60-0.96]) and incident hypertension (RR 0.74 [95% CI 0.56-0.97]). After accounting for body mass index, this relation persisted among obese men (RR for the highest [vs. lowest] adiponectin quartile: 0.59 [95% CI 0.36-0.97] for incident hypertension, and 0.69 [95% CI 0.45-1.06] for BP progression). Among women, adiponectin was not associated with BP outcomes (RR [95% CI] for Q4 vs. Q1: 1.03 [0.86-1.23] and 1.01 [0.83-1.23] for BP progression and incident hypertension, respectively). Our findings were consistent across both the American College of Cardiology (ACC)/American Heart Association (AHA) and Seventh Joint National Committee (JNC-7) BP categories. In a large, community-based sample of AAs, higher adiponectin concentrations were associated with lower risks of BP progression and incident hypertension in men, but no significant association was observed in women.

Association of plasma adiponectin with tumor infiltrating lymphocytes and survival in patients with stage III colon cancer (NCCTG N0147; Alliance).

3591 Background: Adiponectin is a peptide hormone exclusively secreted by adipocytes that plays a role in immune regulation and in the host inflammatory response to cancer. We examined postsurgical adiponectin levels in relationship to tumor infiltrating lymphocytes (TILs), clinicopathological features, vitamin D status, and patient survival in participants in a phase 3 trial of adjuvant chemotherapy. Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon carcinoma who received adjuvant FOLFOX +/- cetuximab. TIL densities were determined at light microscopy in routine histopathological sections. The associations between adiponectin and 25(OH)D, TILs, other factors were evaluated by Fisher’s Exact, Chi-squared, t-test, and Kruskal-Wallis tests where appropriate. The association between adiponectin or 25(OH)D with disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS) were evaluated by multivariable Cox regression, adjusting for body mass index (BMI), race, T, N stage, performance status, tumor location, TILs, BRAF/KRAS, and mismatch repair status. Results: A statistically significant and inverse association between adiponectin level and BMI was observed with lower levels found with obesity (BMI &gt; 30 kg/m2) [p &lt; 0.001]. The level of adiponectin was significantly lower in men vs women (p &lt; 0.001), in blacks vs whites or Asians (p &lt; 0.032), and in patients with fewer regional lymph node metastases (N1 vs N2 stage, p = 0.011). A significantly lower level of adiponectin was found in patients whose tumors had high vs low TIL densities (p = 0.040), but was unrelated to 25(OH)D. Insufficiency of 25(OH)D ( &lt; 30 ng/ml) was detected in 291 (49%) of patients and was not associated with TILs. By multivariable analysis, adiponectin was not associated significantly with patient DFS (HRadj= 0.98, 95% CI 0.74-1.29, padj= 0.88) nor with OS nor time-to-recurrence (TTR). TIL densities were significantly prognostic, but 25(OH)D was not (DFS: HRadj= 1.12, 95% CI 0.85-1.47, padj= 0.44). No significant interaction was observed for adiponectin with TILs for the association with DFS. Conclusions: Lower adiponectin levels were associated with significantly increased TIL densities in colon cancers, indicating an enhanced anti-tumor immune response. In contrast to TILs, adiponectin was not independently associated with patient outcome. Nearly one-half of stage III patients were vitamin D insufficient, although 25(OH)D was not prognostic.

Association of plasma adiponectin with pulmonary hypertension, mortality and heart failure in African Americans: Jackson Heart Study.

BackgroundAdiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear.MethodsWe performed cross-sectional and longitudinal analysis to examine if there is an association between plasma adiponectin and PH and associated clinical outcomes, in participants of Jackson Heart Study (JHS). JHS is a prospective observational cohort study of heart disease in AAs from Jackson, Mississippi.ResultsOf the 3161 participants included in the study, mean age (SD) was 56.38 (12.61) years, 1028 were men (32.5%), and mean (SD) BMI was 31.42 (7.05) kg/m2. Median (IQR) adiponectin was 4516.82 (2799.32–7065.85) ng/mL. After adjusting for potential confounders including BMI, higher adiponectin levels were associated with increased odds of PH (adjusted odds ratio per log increment in adiponectin, (1.81; 95% CI, 1.41–2.32). High adiponectin levels were also associated with associated HF admissions (adjusted hazard ratio [HR] per log increment in adiponectin, 1.63, 95% CI, 1.24–2.14) and mortality (adjusted HR per log increment in adiponectin, 1.20; 95% CI 1.02–1.41).ConclusionsElevated plasma adiponectin levels are associated with PH, HF admissions and mortality risk in AAs. High adiponectin levels may help identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies

Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy.

Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.

Contribution of adiponectin to the cardiometabolic risk of postmenopausal women with loss-of-function lipoprotein lipase gene mutations

Cardiovascular risk significantly increases after menopause. Lipoprotein lipase (LPL) is a key enzyme in the metabolism of triglyceride (TG)-rich lipoproteins, which contributes to cardiometabolic homeostasis. Adiponectin is an adipocytokine, which also influences the cardiometabolic status. The objective of this study was to evaluate the contribution of plasma adiponectin to the cardiometabolic status of women with loss-of-function LPL gene variants (LPLD). A total of 568 white women (127 women with partial LPL deficiency and 441 controls) were included. The association of plasma adiponectin with LPLD was assessed using multiple regression models. Cardiometabolic covariates included anthropometrics, lipids (TG, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B), fasting glucose, and smoking status. Plasma adiponectin concentration was significantly lower in women with LPLD (8.69 ± 5.13 vs 6.50 ± 4.66 μg/mL; P < 0.001). Women with LPLD also presented a significantly higher risk of coronary artery disease (P = 0.013). After menopause, adiponectin explained a significant (P < 0.01) proportion of the variance in cardiometabolic covariates in both groups. This effect was more pronounced in women with LPLD: 13% versus 8% for high-density lipoprotein cholesterol, 8% versus 4% for waist circumference, 9% versus 5% for fasting TG, and 6% versus 2% for fasting glucose. When controlling for cardiometabolic covariates, low adiponectin values independently contributed to the clinical expression of LPLD in postmenopausal women (odds ratio, 5.55; 95% CI, 0.04-0.81; P = 0.025). In conclusion, these results suggest that a low plasma adiponectin level significantly contributes to the cardiometabolic risk profile of postmenopausal women with LPLD, independently of anthropometrics, lipids, and other covariates.

Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome

Plasma adiponectin is negatively correlated with metabolic syndrome (MetS) components obesity and insulin sensitivity. Here, we set out to evaluate the effect of menopause on the association of plasma adiponectin with MetS. Data on plasma adiponectin and MetS were available from 2256 individuals participating in the Erasmus Rucphen Family study. Odds ratios for MetS were calculated by logistic regression analysis using plasma adiponectin quartiles. The discriminative accuracy of plasma adiponectin for MetS was determined by calculating the area under the curve (AUC) of receiver operator. Analyses were performed in women and men, pre- and postmenopausal women and younger and older men. Virtually all determinants of MetS differed significantly between groups. Low plasma adiponectin showed the highest risk for MetS in postmenopausal women (odds ratio = 18.6, 95% CI = 7.9-44.0). We observed a high discriminative accuracy of age and plasma adiponectin for MetS not only in postmenopausal women (AUC = 0.76) but also in other subgroups (AUC from 0.67 to 0.87). However, in all groups, the discriminative accuracy of age and body mass index (BMI) for MetS was similar to the discriminative accuracy of age and plasma adiponectin. Low plasma levels of adiponectin are associated with increased prevalence of MetS, especially in postmenopausal women. Age and BMI have similar discriminatory accuracies for presence of MetS when compared with age and plasma adiponectin. Thus, we conclude that the association of plasma adiponectin with MetS is significantly affected by menopause but challenge the additional value of adiponectin for the discriminatory accuracy for presence of MetS.

Adipocyte volumes and levels of adipokines in diabetes and obesity

Summary Aim Obesity is a major risk factor for insulin resistance, type 2 diabetes, heart disease, and many other chronic diseases. The factors regulating cytokine production seem to have a role on the determination of adipocyte volume. We aimed to investigate the association of plasma adiponectin and resistin concentrations with adipocyte volumes in obese, diabetic, obese–diabetic and control groups. Methods Plasma adiponectin, resistin and lipid levels and adipocyte volumes were investigated in obese, non-diabetic, non-obese diabetic, obese diabetic and control groups consisting 100 subjects who planned to undergo elective surgery. Differences in clinical or laboratory parameters among groups were compared by using one-way ANOVA test. Chi-square test was used for comparing the frequencies. Results The lipid values in all three groups were higher than the control group. A negative correlation was found between adiponectine levels and adipocyte volumes. When adipocyte volumes were compared with other groups, adipocyte volumes were significantly higher in the obese diabetic group ( p = 0.000). The adipocyte volumes in the obese group were determined to be higher than the control group. Conclusions Although a positive correlation was found between adipocyte volumes and adiponectin in literature, adiponectin concentrations in our study were lower. These conditions can be explained by the effect of insulin resistance on the adiponectin levels in obese diabetic groups. Moreover, adiponectin levels are mostly associated with subcutaneous adipose tissue which may have been less. Resistin levels may play an important role in the development of obesity, insulin resistance and diabetes.

Gender differences in association of plasma adiponectin with obesity reflect resultant insulin resistance in non‐diabetic Japanese patients with schizophrenia

Adipose tissues poorly produce adiponectin in the population with increased body fat mass and diabetes mellitus. It was investigated whether hypoadiponectinemia is associated with obesity and insulin resistance in patients with chronically medicated schizophrenia. A cross-sectional study was designed for 73 non-diabetic Japanese patients with schizophrenia. The patients aged <70 years with body mass index (BMI) > or =18.5 were selected. Anthropometrics and blood parameters including fat-derived cytokines were measured, and then the BMI and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. The variables were compared between the non-obesity (BMI, 18.5-24.9) and obesity (> or = 25.0) groups, and between genders. Plasma adiponectin negatively correlated with BMI (r = -0.554, P < 0.0003) and HOMA-IR (r = -0.380, P = 0.007) in men, but not in women. The obesity group in men, as compared with the non-obesity group, showed significantly lower plasma adiponectin (P = 0.008) and higher HOMA-IR (P < 0.05), but not in women. Plasma leptin showed a significant positive correlation with BMI (r = 0.604, P < 0.0001 in men; r = 0.763, P < 0.0001 in women) and HOMA-IR (r = 0.618, P < 0.0001 in men; r = 0.679, P < 0.0001 in women). The mean plasma leptin in the obesity group was significantly higher than that in the non-obesity group (P < 0.01 in men; P < 0.01 in women). In contrast to plasma leptin, plasma adiponectin showed gender difference in relation to BMI and HOMA-IR.

Decreased Plasma Lipoprotein Lipase in Hypoadiponectinemia

Adiponectin is a plasma protein expressed in adipose tissue. Hypoadiponectinemia is associated with low HDL cholesterol and high plasma triglycerides, which also characterize lipoprotein lipase (LPL) deficiency syndromes. Recently, dramatically increased LPL activity was reported in mice overexpressing adiponectin. We therefore speculated that adiponectin may directly affect LPL in humans. We measured plasma adiponectin and postheparin LPL in 206 nondiabetic men and in a second group of 110 patients with type 2 diabetes. Parameters were correlated with markers of systemic inflammation (C-reactive protein [CRP]) and insulin resistance (homeostatis model assessment of insulin resistance [HOMA-IR]). Nondiabetic subjects with decreased plasma adiponectin had lower LPL activity (r=0.42, P <0.0001). This association of plasma adiponectin with LPL activity was confirmed in the second group of patients with type 2 diabetes (r=0.37, P <0.0001). Multivariate analysis revealed that adiponectin was the strongest factor influencing LPL activity, accounting for 23% of the variation in LPL activity in nondiabetic subjects and for 26% of the variation in LPL activity in type 2 diabetic patients. These associations were independent of plasma CRP and HOMA-IR. These results demonstrate an association of decreased postheparin LPL activity with low plasma adiponectin that is independent of systemic inflammation and insulin resistance. Therefore, LPL may represent a link between low adiponectin levels and dyslipidemia in both nondiabetic individuals and patients with type 2 diabetes.