Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study.

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case-control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.

Resistin is associated with biomarkers of inflammation while total and high-molecular weight adiponectin are associated with biomarkers of inflammation, insulin resistance, and endothelial function.

OBJECTIVE: Adiponectin and resistin have been linked to inflammation, endothelial dysfunction, and/or insulin secretion or resistance. It remains to be elucidated which of these adipokines is associated primarily with biomarkers of all or only some of these categories, i.e. biomarkers of inflammation, endothelial dysfunction, and/or insulin secretion or insulinemia. DESIGN AND METHODS: We studied 1065 healthy women, Nurses' Health Study participants, who provided blood samples in 1989-1990. A cross-sectional analysis was conducted to assess the relationships between total and high-molecular weight (HMW) adiponectin and resistin with inflammatory markers and biomarkers of endothelial dysfunction, insulin secretion, and insulinemia. RESULTS: Resistin was positively associated with the inflammatory markers soluble tumour necrosis factor-alpha receptor II and interleukin-6 but not with any biomarkers of endothelial function, glycemia, insulinemia, or markers of insulin secretion after multivariate adjustment for age and body mass index (BMI). In both crude and multivariate analyses, total adiponectin was inversely associated with insulin, proinsulin, C-peptide, HbA1c, sE-selectin, and C-reactive protein (CRP) levels. HMW adiponectin was inversely associated with circulating insulin, proinsulin, C-peptide, HbA1c, sE-selectin, and CRP concentrations, even after adjustment for age, BMI, lifestyle factors, exercise, the use of medications as well as the other biomarkers of interest. Total and HMW adiponectin demonstrated negative associations with soluble intercellular adhesion molecule-1, which became nonsignificant after adjustment for confounders, whereas positive associations between soluble vascular cell adhesion molecule-1 and total adiponectin became significant only after multivariate adjustment. CONCLUSIONS: Total and HMW adiponectin are inversely associated with markers of insulin secretion/insulinemia, endothelial function, and inflammation. Resistin is positively associated only with markers of inflammation.

Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: a prospective cohort study.

OBJECTIVES: Leptin and adiponectin are adipocyte-secreted hormones that regulate energy homeostasis and metabolism. Because their roles in the neonatal period and in early childhood are poorly understood, we aimed in this prospective cohort study to determine the extent to which umbilical cord blood leptin and adiponectin concentrations predict measures of adiposity and growth at 3 years of age. PATIENTS AND METHODS: We studied 588 children participating in the prospective prebirth cohort study Project Viva. We examined associations of cord blood leptin and adiponectin levels with weight changes during the first 6 months of life, 3-year circulating leptin and adiponectin concentrations, and the following adiposity-related outcomes at 3 years of age: BMI z score, height-for-age z score, and sums of triceps and subscapular skinfold thicknesses to represent overall adiposity, as well as subscapular/triceps skinfold ratio to represent central adiposity. RESULTS: Cord blood leptin and adiponectin were each directly associated with the duration of gestation and birth weight for gestational age z scores. Cord blood leptin levels were negatively associated with change in weight-for-length, weight-for-age, and length-for-age z scores between birth and 6 months of age. Similarly, cord blood adiponectin was negatively associated with change in weight-for-length and weight-for-age z scores. After adjusting for several maternal and child factors related to obesity, each 10 ng/mL increment of cord blood leptin was associated with a reduction in BMI z score and higher leptin levels at 3 years but not with skinfold thicknesses. Each 10 microg/mL increment of cord blood adiponectin was positively associated with a higher subscapular skinfold thickness/triceps skinfold thickness ratio at 3 years. CONCLUSIONS: Lower cord blood leptin levels are associated with smaller size at birth but more pronounced weight gain in the first 6 months of life and higher BMI at 3 years of age. Cord blood adiponectin levels are also directly associated with birth weight for gestational age, inversely associated with weight gain in the first 6 months of life, and predict an increase in central adiposity at age 3 years.

Phobic anxiety is associated with higher serum concentrations of adipokines and cytokines in women with diabetes.

OBJECTIVE: Phobic anxiety has been associated with increased risk of cardiovascular disease (CVD), but the underlying mechanisms are poorly understood. We aimed to determine whether associations of phobic anxiety with several known markers of CVD might be contributors. RESEARCH DESIGN AND METHODS: We used a 16-point validated index (Crown-Crisp) measured in 1988 to categorize 984 women with type 2 diabetes from the Nurses' Health Study as having low, moderate, or high phobic anxiety. Groups were then compared for differences in adipokines (adiponectin and leptin), inflammatory markers (C-reactive protein and tumor necrosis factor [TNF]-alpha receptor II), and markers of endothelial function (sE-selectin, soluble intercellular adhesion molecule [sICAM]-1) measured on blood samples provided between 1989 and 1990. RESULTS: Higher levels of phobic anxiety were associated with higher BMI and lower education. Higher levels of phobic anxiety were also associated with higher leptin and soluble TNF-alpha receptor II in both crude analyses and after adjustment for potential confounders. sICAM and sE-selectin were higher in the highest tertile compared with the middle tertile, but there was no significant trend across tertiles. We found no association between phobic anxiety and adiponectin. CONCLUSIONS: High levels of phobic anxiety are associated with increased levels of leptin and inflammatory markers, which may in part explain the previously observed relationship between anxiety and other psychosocial disorders with CVD.

Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study.

BACKGROUND: Adherence to a healthy dietary pattern, such as the Alternate Healthy Eating Index (AHEI), is associated with a lower risk of diabetes and atherosclerosis. OBJECTIVE: We aimed to determine whether adherence to the AHEI is associated with higher plasma total and high-molecular-weight (HMW) adiponectin concentrations and lower concentrations of resistin, as well as biomarkers of inflammation, endothelial dysfunction, and insulin resistance. DESIGN: The study evaluated 1922 women from the Nurses' Health Study (62% of whom were overweight) who had no history of diabetes or cardiovascular disease. Their plasma biomarker concentrations were measured in 1990, and data on dietary intake from semiquantitative food-frequency questionnaires administered in 1984, 1986, and 1990 were averaged to account for long-term dietary exposure and to reduce within-subject variability. RESULTS: After adjustment for age and energy intake, women with the highest adherence to the AHEI had 24% higher median total adiponectin and 32% higher median HMW adiponectin concentrations, as well as 16% lower resistin, 41% lower CRP, 19% lower sE-selectin, and 24% lower ferritin concentrations (P < 0.01 for all) than did women with the lowest adherence to the AHEI. These associations remained significant after adjustment for potential confounders. Inverse associations between the AHEI and soluble tumor necrosis factor-alpha receptor II, interleukin-6, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, C-peptide, insulin, and glycated hemoglobin were evident, but they were not significant after adjustment for body mass index. CONCLUSION: The preventive effects of healthier dietary patterns on risk for diabetes and atherosclerosis may be mediated by improvements in plasma concentrations of adipokines or other biomarkers of risk for diabetes and cardiovascular disease.

Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study.

To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1,058 nondiabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank >or=4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 microg/ml, respectively, in diabetic women, P = 0.004; 15.0 vs. 13.2 microg/ml in nondiabetic women, P = 0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein, and tumor necrosis factor-alpha receptor II. Adjustment for adiponectin did not weaken these associations, and adjustment for inflammatory markers did not attenuate the association between coffee consumption and adiponectin concentrations. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.