Plasma Adipokine Concentrations Research Articles

A Prospective Study of Circulating Adipokine Levels and Risk of Multiple Myeloma

Abstract Purpose: Obesity is associated with an increased risk of multiple myeloma (MM), although the biologic mechanisms underlying this association are unclear. We conducted a nested case-control study in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to evaluate the hypothesis that altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue, may partly explain the association between obesity and MM. Methods: We investigated whether circulating levels of leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin are associated with MM among 174 cases and 348 controls in PLCO. Two controls were matched to each case on age at baseline, sex, race, date of phlebotomy, time of day of phlebotomy, and study year of specimen collection. Plasma adipokine concentrations were measured by enzyme-linked immunosorbent assay; overall coefficients of variation were ≤8.5%. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: Inverse associations with MM were observed for total adiponectin (highest quartile vs. lowest: OR = 0.49, 95% CI = 0.26–0.93, P-trend = 0.03) and HMW adiponectin (OR = 0.44, 95% CI = 0.23–0.85, P-trend = 0.01). These associations remained after adjusting for body mass index (BMI), stratifying by sex, and restricting to cases diagnosed approximately eight years or more after blood collection. We observed a modest association between BMI and MM (OR per 5 kg/m2 increase = 1.14, 95% CI = 0.94–1.39), which was attenuated by approximately 40% after adjusting for adiponectin. Leptin levels were not associated with MM. Conclusions: These results suggest that higher circulating levels of adiponectin are protective against MM, and that adiponectin may play an important role in obesity-related myelomagenesis. This study is, to our knowledge, the first prospective investigation of circulating adipokines and MM. Our findings are particularly intriguing in light of recent evidence that host-derived adiponectin is tumor-suppressive and a potential novel therapeutic target for MM and associated bone disease.

Adipokines, Ghrelin and Obesity‐Associated Insulin Resistance in Nondiabetic Patients with Acute Coronary Syndrome

Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity-related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA(IR))-insulin resistance index, plasma adiponectin, leptin, total (T-Ghrelin), acylated (Acyl-Ghrelin), and desacylated ghrelin (Desacyl-Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non-ACS, ACS patients had similar HOMA(IR) and plasma adipokines, but lower T- and Desacyl-Ghrelin and higher Acyl-Ghrelin. Obesity (BMI > 30) was associated with higher HOMA(IR), lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non-ACS subjects. In ACS (n = 60) HOMA(IR) remained associated negatively with adiponectin and positively with leptin independently of BMI and c-reactive protein (CRP) (P < 0.05). On the other hand, low T- and Desacyl-Ghrelin with high Acyl-Ghrelin characterized both obese and non-obese ACS patients and were not associated with HOMA(IR). In conclusion, in ACS patients, obesity and obesity-related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.

Adipokines in Plasma and Breast Tissues: Associations with Breast Cancer Risk Factors

Blood adipokines are associated with breast cancer risk; however, blood-breast adipokine correlations and factors that explain variation in adipokines are unknown. Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations. Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma-breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma-breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin. Although we report positive plasma-breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis. A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues.

Effect of Low-Dose Atorvastatin on Plasma Concentrations of Adipokines in Patients with Metabolic Syndrome

Objective: It has not been conclusively proven whether or not the beneficial effect of statins on the cardiovascular system is mediated through their influence on adipokine secretion. We designed a prospective open-label study to assess the influence of 6 months’ atorvastatin therapy on plasma concentrations of some adipokines in patients with metabolic syndrome. Subjects: 36 adult patients with metabolic syndrome and serum LDL cholesterol >3.5 mmol/l, previously untreated with statins, were included in the study. Measurements: Plasma concentrations of adiponectin, leptin, resistin and insulin were measured before initiation and after 2, 4 and 6 months of atorvastatin therapy (10 mg), and 2 months after treatment cessation. Results: Treatment with atorvastatin was followed by a 35.6% decline in LDL cholesterol. Plasma adiponectin concentration decreased by 20.7% after 2 months; however, after 4 and 6 months, this did not differ significantly from the initial values. There was a negative correlation between the initial plasma concentration of leptin and changes in HDL cholesterol (R = –0.358; p = 0.04). Conclusions: Firstly, the long-term effect of atorvastatin therapy in patients with metabolic syndrome is not mediated by changes in the secretion of adiponectin, leptin and resistin by adipose tissue. Secondly, plasma leptin concentration seems to be a predictor of HDL cholesterol changes during atorvastatin therapy.

Telmisartan Improves Cardiometabolic Profile in Obese Patients with Arterial Hypertension

Objective: There are several lines of evidence that telmisartan may improve cardiometabolic profile. The aim of the study was to estimate changes of insulin resistance and plasma concentrations of adipokines after long-term antihypertensive treatment with telmisartan in obese hypertensive patients. Methods: 34 previously untreated obese adults with arterial hypertension were enrolled. Glucose cellular uptake (M value) and the M to insulin ratio (M/I value) were measured by euglycemic-hyperinsulinemic clamp technique, body fat content (by dual-energy X-ray absorptiometry method), as well as plasma concentrations of selected adipokines and cytokines were estimated before and after 6-month telmisartan therapy in 25 patients who completed the study. Results: Telmisartan therapy was followed by 14.2% decrease of systolic and by 19.6% decrease of diastolic blood pressure. Body fat mass did not change significantly. Both M and M/I values (by 24.4 and by 38.6%, respectively) as well as plasma levels of total and high-molecular-weight adiponectin (by 10.8 and by 23.5%, respectively) increased significantly. Plasma concentrations of high-sensitivity C- reactive protein and interleukin-8 decreased significantly, while those of interleukin-6 and tumor necrosis factor-α tended to decline. Conclusions: Telmisartan monotherapy improves cardiometabolic profile in obese hypertensive patients by improving insulin sensitivity and increasing of plasma adiponectin concentration, including its high-molecular-weight fraction, and by suppressing of microinflammation.

A Randomized Controlled Intervention With Fish Oil Versus Sunflower Oil From 9 to 18 Months of Age: Exploring Changes in Growth and Skinfold Thicknesses

n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), from fish oil (FO), in rodents have been shown to reduce adipogenesis. Evidence of an effect on adipose tissue mass in humans is limited, and no studies have specifically aimed to elucidate this in infancy. To explore whether n-3 LCPUFA intake affects adipose tissue growth, we randomly allocated 154 healthy infants to daily supplementation with FO or sunflower oil (SO) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessments of body size and skinfold thicknesses and plasma adipokine concentrations. Among the 133 completing infants, erythrocyte n-3 PUFA increased more in those receiving FO than in infants receiving SO [12.2 ± 0.7 (mean ± SE) versus 2.0 ± 0.4 fatty acid percentage (FA%), p < 0.001] with a concomitant larger decrease in n-6 PUFA (-8.9 ± 0.7 versus -0.9 ± 0.6 FA%, p < 0.001). We found no association between FO consumption relative to SO consumption and any of the anthropometric measures related to the size of the fat mass, but infants in the FO group had a lower skinfold ratio (triceps/subscapular) at 18 mo than those in SO group (p = 0.02). Our findings do not support the hypothesis that dietary n-3 LCPUFA is important for infant fat mass, but future studies testing this specifically are warranted.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

AimsThe aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes.MethodsA 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat.ResultsForty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat.ConclusionsA calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

Abstract A88: Differences in plasma and breast tissue adipokine levels by race and obesity status

Abstract Background: Adipokines, specifically leptin and adiponectin, are directly linked to obesity and it has been suggested that they may contribute to breast carcinogenesis as well. High plasma leptin and low adiponectin concentrations are associated with high levels of body fat, and similar associations have been reported for breast cancer risk. However, little is known about the concentrations of these hormones in breast tissue and if they influence the tissue microenvironment to modify breast cancer risk. Moreover, few studies have investigated racial/ethnic differences in adipokine concentrations and how these differences determine adipokine predictors in different groups. Methods: Plasma and breast tissues collected from one hundred twelve women (67 European American (EA) women and 45 African American (AA) women), without breast cancer, undergoing reduction mammoplasty surgery were analyzed for leptin and adiponectin concentrations. Tissue and plasma leptin and adiponectin were quantified by commercially available enzyme-linked immunosorbent assays (R&amp;D Systems, Minneapolis, MN). Tissue adipokine concentrations were adjusted by total protein concentration (reported as nanograms of hormone per milligram of protein (ng/mg of protein)). Assays were highly reproducible and all CVs were ≤9.3%. Spearman rank correlation coefficients were used to describe associations between plasma and tissue adipokine concentrations as well as associations among adipokine concentrations and selected breast cancer risk variables. Two-way ANOVAs were used to determine associations between adipokine concentrations and race and obesity status. Results: Overall, AAs had significantly higher plasma and tissue leptin and lower plasma adiponectin concentrations than EAs. They also had significantly lower adiponectin to leptin ratios in both plasma and tissue. There was no significant difference in tissue adiponectin concentrations between EAs and AAs. Obese women had significantly higher plasma and tissue leptin than non-obese women, but no significant difference in plasma and tissue adiponectin concentrations were observed. Generally, there were several significant associations observed among plasma and tissue adipokines and selected breast cancer risk variables; however several of these associations were attenuated in AAs and non-obese women. Plasma and tissue leptin correlated well in EAs, but not in AAs. There was no correlation between plasma and tissue adiponectin concentrations in any individual group, but when combined there was a marginal association. Conclusions: We found differences by race/ethnicity and by obesity status in adipokines in tissue and blood. Additionally, we found a lack of association between circulating adiponectin and breast tissue levels for AA women. If adipokines play a role in carcinogenesis in the breast, there may be effect modification by race/ethnicity and by body weight. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A88.

Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients

Elevated plasma free fatty acid (FFA), inflammatory marker, and altered adipokine concentrations have been observed in obese type 2 diabetes patients. It remains unclear whether these altered plasma concentrations are related to the diabetic state or presence of obesity. In this cross-sectional observational study, we compare basal plasma FFA, inflammatory marker, and adipokine concentrations between obese and non-obese type 2 diabetes patients and healthy, non-obese controls. A total of 20 healthy, normoglycemic males (BMI <30 kg/m2), 20 non-obese (BMI <30 kg/m2) and 20 obese (BMI >35 kg/m2) type 2 diabetes patients were selected to participate in this study. Groups were matched for age and habitual physical activity level. Body composition, glycemic control, and exercise performance capacity were assessed. Basal blood samples were collected to determine plasma leptin, adiponectin, resistin, tumor necrosis factor α (TNFα), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and FFA concentrations. Plasma FFA, inflammatory marker (hsCRP, IL-6, TNFα), adipokine (adiponectin, resistin, leptin), and triglyceride concentrations did not differ between non-obese diabetes patients and healthy, normoglycemic controls. Plasma FFA, IL-6, hsCRP, leptin, and triglyceride levels were significantly higher in the obese diabetes patients when compared with the healthy normoglycemic controls (P < 0.05). Furthermore, plasma hsCRP and leptin levels were significantly higher in the obese versus non-obese diabetes patients (P < 0.05). Significant correlations between plasma parameters and glycemic control were observed, but disappeared after adjusting for trunk adipose tissue mass. Elevated plasma leptin, hsCRP, IL-6, and FFA concentrations are associated with obesity and not necessarily with the type 2 diabetic state.

Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index

Hyperinsulinemia is a characteristic of type 2 diabetes mellitus (T2DM) and is believed to play a role in the low-grade inflammation seen in T2DM. The main aim was to study the effect of hyperinsulinemia on adipokines in individuals with different levels of insulin resistance, glycemia, and obesity. Three groups of sex-matched subjects were studied: young healthy subjects (YS; n = 10; mean age, 26 years; body mass index [BMI], 22 kg/m 2), patients with T2DM (DS; n = 10; 61 years; BMI, 27 kg/m 2), and age- and BMI-matched controls to DS (CS; n = 10; 60 years; BMI, 27 kg/m 2). Plasma concentrations of adipokines were measured during a hyperinsulinemic euglycemic clamp lasting 4 hours. Moreover, insulin-stimulated glucose uptake in isolated adipocytes was analyzed to address adipose tissue insulin sensitivity. Plasma interleukin (IL)-6 increased significantly ( P ≤ .01) in all 3 groups during hyperinsulinemia. However, the increase was smaller in both DS ( P = .06) and CS ( P < .05) compared with YS (∼2.5-fold vs ∼4-fold). A significant increase of plasma tumor necrosis factor (TNF) α was observed only in YS. There were only minor or inconsistent effects on adiponectin, leptin, and high-sensitivity C-reactive protein levels during hyperinsulinemia. Insulin-induced rise in IL-6 correlated negatively to BMI ( P = .001), waist to hip ratio ( P = .05), and baseline (fasting) insulin ( P = .03) and IL-6 ( P = .02) levels and positively to insulin-stimulated glucose uptake in isolated adipocytes ( P = .07). There was no association with age or insulin sensitivity. In a multivariate analysis, also including T2DM/no T2DM, an independent correlation (inverse) was found only between BMI and fold change of IL-6 ( r 2 = 0.41 for model, P < .005). Hyperinsulinemia per se can produce an increase in plasma IL-6 and TNF α, and this can potentially contribute to the low-grade inflammation seen in obesity and T2DM. However, obesity seems to attenuate the ability of an acute increase in insulin to further raise circulating levels of IL-6 and possibly TNF α.

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-α 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.

Effects of long-term exercise and diet intervention on plasma adipokine concentrations

Background: In a randomized, controlled, 2 × 2 factorial trial on the effect of long-term changes in diet and exercise, a significant reduction in body weight and fat mass was observed. Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study.Objective: We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines; adiponectin, interleukin-6 and -8, tumor necrosis factor-α, monocyte chemoattractant protein-1, hepatocyte growth factor, nerve growth factor, C-reactive protein, and resistin.Design: One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were randomly allocated to 4 groups: diet, exercise, combined diet and exercise, and control.Results: Plasma adiponectin concentrations remained unchanged, whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity. In the control group, adiponectin concentrations were reduced. Analyzed according to the factorial design, only diet intervention had a significant (P = 0.03) positive effect on plasma adiponectin relative to control, and this effect was largely explained by changes in fat mass. After adjustment for change in percentage body fat, there were significant positive effects on tumor necrosis factor-α in all 3 intervention groups (P = 0.01 for the diet group, 0.03 for the exercise group, and 0.05 for the combined diet and exercise group). Minor changes were observed for the other adipokines. Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines, whereas concentrations of and changes in the other adipokines were significantly correlated.Conclusion: Diet intervention had a significant positive effect on adiponectin concentrations, which is largely explained by a reduction in fat mass.

Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate and the resultant effects of plasma insulin, adipokine, and lipid concentrations may affect cardiomyocyte size and function, particularly in the setting of chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats ca affect cardiac growth, metabolism, and function, mainly in the context of pressure overload-induced LVH.

Diet/ExerciseVersusPioglitazone: Effects of Insulin Sensitization with Decreasing or Increasing Fat Mass on Adipokines and Inflammatory Markers

Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.

Differential effects of peroxisome proliferator-activated receptor ligands and sulfonylurea plus statin treatment on plasma concentrations of adipokines in type 2 diabetes with dyslipidemia

Peroxisome proliferator-activated receptor gamma is the master regulator of adipocyte differentiation and controls many adipocyte genes in response to anti-diabetic thiazolidinediones (TZDs) and lipid-lowering fibrates. We hypothesized that the combination of TZD+fibrate may be better than the sulfonylurea + statin approach regarding modifying the adipokine profile in diabetic patients with dyslipidemia. We measured the lipid profiles and circulating levels of adiponectin, resistin, and inflammatory markers before and after treatment in 24 type 2 diabetic patients with dyslipidemia (aged 64+/-9 years; M/F=5/19). The study patients were randomly assigned to receive an 8-week treatment of either rosiglitazone 4 mg daily and fenofibrate 160 mg daily (PPAR group) or glibenclamide 5 mg daily and atorvastatin 10 mg daily (non-PPAR group). Even though the administration of sulfonylurea+statin can achieve a greater reduction of total cholesterol and LDL-cholesterol levels and a comparable glucose control compared to PPAR treatment, their administration did not change the plasma adipokine levels significantly. In contrast, a significant greater increase of the plasma concentrations of adiponectin (P<0.0001), a trend to a greater decrease of the plasma resistin levels (P=0.061), a significantly greater increase of HDL-cholesterol (P=0.002), and a significantly greater reduction of triglyceride levels (P=0.018) were seen in the PPAR group. Considering the clinical significance of the adipokine-endothelial interaction in the progression and long-term prognosis of atherosclerosis, the differential effects of PPAR ligands and sulfonylurea+statin on plasma adipokine concentrations demonstrated in this study are interesting foci of investigation in the future.