Adipokines In Patients Research Articles

The Impact of Type 2 Diabetes on Circulating Adipokines in Patients with Metabolic Syndrome

Aim: The aim of the study was to investigate, whether type 2 diabetes independently influences adipokines and inflammatory markers in patients with metabolic syndrome. Methods: 36 patients with metabolic syndrome without type 2 diabetes and 39 patients with metabolic syndrome with type 2 diabetes, carefully matched for age, sex, and BMI, were investigated. Primary outcome measures were circulating adipokines and inflammatory markers (adiponectin, leptin, visfatin, vaspin, resistin, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), retinol binding protein 4 (RBP-4), growth differentiation factor-15 (GDF-15)). In addition, we determined parameters of glucose and lipid metabolism. Results: Patients with metabolic syndrome and type 2 diabetes had significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides (p < 0.05). They displayed higher GDF-15 concentrations (1,113 ± 135 vs. 656 ± 63 pg/ml, p = 0.005) and lower visfatin concentrations (3.7 ± 0.3 vs. 4.8 ± 0.2 ng/ml, p = 0.009). There were no differences in other adipokines and inflammatory markers between both groups. Conclusions: In patients with metabolic syndrome, type 2 diabetes leads to decreased visfatin and increased GDF-15 serum levels when compared to carefully matched non-diabetic subjects. Whether the increase in GDF-15 is an indicator or a causal factor for the increased cardiovascular risk in diabetic subjects remains to be investigated in further studies.

The impact of aerobic exercise training on novel adipokines, apelin and ghrelin, in patients with type 2 diabetes

SummaryBackgroundAccumulating data support the atheroprotective role of the novel adipokines, apelin and ghrelin. The aim of the present randomized study was to investigate the effects of aerobic exercise training on these adipokines in patients with type 2 diabetes mellitus (T2DM).Material/MethodsFifty-four overweight (BMI >25 kg/m2) patients with T2DM, but without vascular complications, were randomized to either the aerobic exercise training group (EG, N=27), 4 times/week, 45–60 min/session; or to the control group (CG, N=27), orally instructed to increase physical activity. Clinical glycemic and lipid parameters, exercise capacity (VO2peak), insulin, HOMA-IR, and serum levels of apelin and ghrelin were assessed at baseline and after 12 weeks.ResultsAerobic exercise significantly improved lipid and glycemic profile and insulin sensitivity compared to CG (p<0.05). Furthermore, between-groups comparison showed a considerable exercise-induced upregulation in apelin (p=0.007) and VO2peak (p<0.001) levels. Negligible changes in body-weight, waist-hip ratio and ghrelin concentrations were detected within and between groups after the completion of the study (p>0.05). However, subgroup analysis revealed a considerable increment in ghrelin levels only in the exercise-treated women compared to their control counterparts (p=0.038). LDL and HOMA-IR reduction were found to be independent predictors of apelin increment in multiple regression analysis (R2=0.391, p=0.011).ConclusionsIn patients with T2DM, systemic, long-term, aerobic exercise exerts positive effects on apelin and ghrelin (only in women), even in the absence of significant weight loss, suggesting its pleiotropic effects.

The association of physical activity with novel adipokines in patients with type 2 diabetes

BackgroundAdipose-tissue derivatives, known as adipokines, have been involved in the inflammatory-mediated metabolic and cardiovascular disorders of type 2 diabetes mellitus (T2DM). This study examined the association between novel adipokines and self-reported physical activity, a potential anti-inflammatory mediator. MethodsWe enrolled 247 men and women with T2DM, free from overt cardiovascular disease. Based on a physical activity questionnaire, patients were classified into groups: A) sedentary, who did not report any physical activity or reported light activities<2h/week and B) active, referring to low or moderate-intensity physical activities>2h/week. Among them, 88 patients were randomly selected to perform a cardiorespiratory ergocycle testing. Clinical parameters, glycemic and lipid profiles, HOMA-IR, and serum levels of visfatin, apelin, vaspin, ghrelin and adiponectin were assessed. ResultsWith the exception of fat-mass, our groups did not differ in anthropometric parameters and pharmaceutical regimen. Active patients showed ameliorated glucose regulation, HOMA-IR, hsCRP and exercise capacity compared to sedentary counterparts (p<0.01). Active rather than sedentary patients showed lower visfatin (10.16±5.53ng/ml vs 14.77±8.48ng/ml, p=0.013), higher apelin (1.39±0.65ng/ml vs 1.04±0.35ng/ml, p=0.018) and adiponectin (11.82±3.06μg/ml vs 7.81±2.11μg/ml, p=0.033) levels. There were non-significant differences in the rest of parameters between groups. After adjusting for age, sex and BMI, physical activity along with hsCRP and ghrelin remained independent determinants of visfatin levels (R2=0.328, p=0.032), while physical activity was independently associated with apelin (R2=0.221, p=0.022). ConclusionsSelf-controlled physical activity of, even, moderate intensity ameliorates adipokines, such as visfatin, apelin and adiponectin, in patients with T2DM. Prospective interventional studies will confirm our results.The ClinicalTrials.gov identifier is: NCT00306176.

Dynamics in Insulin Resistance and Plasma Levels of Adipokines in Patients With Acute Decompensated and Chronic Stable Heart Failure

Background Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery. Methods and Results We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 wk) and late (> 6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients. Conclusions ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF.

Serum adipokine profiles in Kawasaki disease

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.

Elevated resistin opposed to adiponectin or angiogenin plasma levels as a strong, independent predictive factor for the occurrence of major adverse cardiac and cerebrovascular events in patients with stable multivessel coronary artery disease over 1-year follow-up

SummaryBackgroundAdipokines such as adiponectin and resistin, as well as angiogenin, may be associated with inflammation and atherosclerosis. The relationship between their levels and prognosis in high risk patients is, however, still unclear. The aim of this study was to evaluate the prognostic value of these adipokines in patients with stable multivessel coronary artery disease (MCAD).Material/MethodsThe study group comprised 107 MCAD patients (74% males, mean age 63±8 years). Adiponectin, resistin and angiogenin plasma levels were measured at admission and after 1-year follow-up. Primary end point (major adverse cardiac and cerebrovascular events – MACCE) was defined as cardiac death, nonfatal myocardial infarction, stroke, and hospitalization for angina or heart failure over a 1-year period.ResultsAfter 1-year follow-up, 9 (8%) patients died, all from cardiovascular causes. Primary end point was experienced by 32% of patients. Surgical treatment (CABG) was received by 51% of patients, while 49% were treated medically alone. Total cholesterol concentration levels ≥173 mg/dl were associated with a 7-fold increase (OR 7.3; 95% CI, 1.6–33.0); LDL ≥93.5 mg/dl with a 16-fold increase (OR 16.3; 95% CI, 2.8–93.8), and resistin ≥17.265 ng/ml with a 13-fold increase in MACCE risk (OR 13.5; 95% CI, 2.3–80.3). In multivariate analysis, a medical treatment strategy (p=0.001), a higher CCS class (p=0.004), resistin levels (p=0.003) and a higher Gensini score (p=0.03) were independent predictors of MACCE.ConclusionsIn stable patients with MCAD, elevated plasma resistin (as opposed to adiponectin or angiogenin) is a strong, independent predictive factor for the occurrence of MACCE over 1-year follow-up.

Elevated Serum Levels of Resistin, Leptin, and Adiponectin are Associated with C-reactive Protein and also Other Clinical Conditions in Rheumatoid Arthritis

Body fat is an important source of hormones and cytokines (adipokines) that not only regulate the energy balance, but also regulate the inflammatory and immune responses. This study investigated the association of clinical conditions with serum levels of adipokines in patients with rheumatoid arthritis. Serum levels of resistin, leptin, and adiponectin were measured by enzyme-linked immunosorbent assay in 141 patients (110 women) who fulfilled the 1987 revised criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis and in 146 normal controls (124 women). Then the correlations between adipokine levels and clinical parameters were evaluated. The serum resistin level did not differ between the patients and controls. However, serum leptin levels were significantly higher in male and female rheumatoid arthritis patients than in the corresponding controls, while the serum adiponectin level was significantly higher in female patients than in female controls. Multivariate analysis revealed that predictors of an elevated resistin level were female sex and C-reactive protein (CRP), while the leptin level was related to the body mass index and CRP. Predictors of an elevated adiponectin level were the use of prednisolone and CRP, however, CRP was negatively associated with adiponectin in patients with rheumatoid arthritis. The serum levels of resistin and leptin were positively associated with CRP level in patients with rheumatoid arthritis, suggesting that these adipokines may act as pro-inflammatory cytokines in this disease. The serum adiponectin level was elevated in the patients, however, it was negatively associated with CRP level. In addition, the serum levels of resistin, leptin, and adiponectin were also associated with female sex, BMI and the use of prednisolone, respectively.

Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome.

Adipose tissue synthesizes various adipokines such as resistin, adiponectin and visfatin, which have an effect on insulin resistance. This study was designed to show the effect of metformin, one of the most important drugs used to reduce insulin resistance in patients with polycystic ovary syndrome (PCOS), on these adipokines. The study group consisted of 24 women with PCOS and 25 healthy, age- and weight-matched, normally menstruating women. Hormone and lipid profiles, visfatin, adiponectin and resistin were measured in all cases, before and after metformin treatment. Serum visfatin levels were found to be significantly higher in patients with PCOS, compared to controls. Following metformin treatment, a significant decrease was observed in visfatin levels compared to the baseline. A positive correlation was found between serum visfatin levels and BMI, waist circumference, HOMA, insulin and triglyceride levels. No statistically significant difference was observed in terms of serum adiponectin levels in women with PCOS before and after treatment, or in healthy controls. Serum resistin levels were significantly reduced by metformin treatment. These findings suggest that visfatin may be related to the obesity and insulin resistance that is frequently encountered in patients with PCOS. A reduction in serum visfatin and resistin levels was shown with metformin treatment, in patients with PCOS.

L-Carnitine Supplementation and Adipokines in Patients with End-Stage Renal Disease on Regular Hemodialysis

Chronic hemodialysis (HD) patients frequently encounter carnitine depletion, elevated adipose tissue-derived hormones/cytokines, that may contribute to accelerated arteriosclerosis. 10 non-diabetic HD patients were studied over 28 weeks. In the 12 weeks treatment period 1 g L-carnitine was given iv after each HD session. Measurements of plasma free- and acylcarnitines, insulin, leptin, adiponectin, resistin and ghrelin were performed at baseline, at weeks 2, 4, 8, 12 (treatment period) and at weeks 24-28 (post-treatment period). L-carnitine supplementation resulted in progressive increase of free- and acylcarnitine levels. Plasma levels of insulin, resistin, leptin and ghrelin remained at the already elevated baseline values. L-carnitine therapy induced a significant increase in plasma adiponectin from 20.2 ± 12.7 μg/ml (baseline) to 32.7 ± 20.2 μg/ml in week 2 (p<0.05) and 35.4 ± 19.6 μg/ml in week 12 (p < 0.03), which remained unchanged in the post-carnitine period. Plasma insulin levels correlated positively with leptin (r = 0.525, p<0.0001) and resistin (r = 0.284, p<0.005); adiponectin levels correlated inversely with leptin (r = -0.255, p<0.02) and resistin (r = -0.213, p<0.04) irrespective of carnitine status. Plasma levels of adipokines and related hormones are greatly elevated in patients on regular HD. L-carnitine administration further augmented the plasma levels of protective adiponectin, therefore it may have a role in preventing cardiovascular complications of uremia.

Relationship between epicardial adipose tissue adipocyte size and MCP-1 expression

Adipocyte size has been associated to increase in inflammatory cytokines expression that can be related to the cardiovascular risk of obesity. Epicardial adipose tissue (EAT) was discovered to play a key role in cardiovascular diseases by producing several inflammatory adipokines. We sought to study whether EAT and subcutaneous adipose tissue (SAT) mean adipocyte sizes are related to the expression of adipokines in patients with cardiovascular diseases. We collected EAT, SAT and blood samples from 22 patients aged 70.9 (s.d. 10.3) undergoing heart surgery. Monocyte chemoattractant protein (MCP)-1, interleukin (IL)-10 and tumor necrosis factor (TNF)-α were analyzed by real time RT-PCR, ELISA or immunohistochemistry. Hematoxylin–eosin staining was used for adipocyte area calculations. Adipocyte size is negatively correlated to MCP-1 expression ( r = −0.475; p = 0.034) in EAT and positively correlated in SAT ( r = 0.438; p = 0.047). These trends persisted after stratification for sex and coronary artery disease (CAD), but only the relationship between EAT MCP-1 and adipocyte size reached statistical significance in the larger group of men with CAD. We have observed that SAT adipocyte size is correlated to BMI ( r = 0.601; p = 0.003); whereas only a non-statistically significant trend was observed in EAT. IL-10 and TNF-α expression were not associated to adipocyte size in EAT nor SAT. Secondarily, we found that EAT IL-10 expression is higher in patients with CAD. These results suggest that adipocyte size is a negative determinant of MCP-1 expression in EAT and a positive determinant in SAT. These data might partly explain the different implications of EAT and SAT in cardiovascular diseases.

The Effects Of Different Exercise Modalities On Adipokines In Patients With Type 2 Diabetes

PURPOSE: Novel adipose-tissue derived cytokines, such as visfatin (nampt) and ghrelin, have emerged as novel cardiovascular risk factors. However, there is limited evidence about the exercise influence on these adipokines in patients with type 2 diabetes (T2D). The aim of our study was to evaluate the effects of different exercise modalities on novel adipokines in T2D. METHODS: 100 patients with T2D, aged 50-65 years, were equivalently (N=25) randomized into 4 groups: A) Control patients remained sedentary throughout the study; B) Supervised aerobic exercise (3 times/week, 45min/session, 60-80%VO2peak). C) Resistance training (similar characteristics as in group B, 60-80% baseline 1-RM). D) Exercise counselling to perform physical activity according to American Diabetes Association. All participants had no diabetic vascular complications and poor glycemic control (HbA1c>6.5%), despite the oral anti-diabetic regimen. At baseline blood samples and clinical parameters were obtained and participants underwent a gradually incremental exercise test on an ergocycle. Blood sampling and measurements were repeated after 6 months. Data were analyzed using ANOVA for repeated measures. RESULTS: At baseline there was no significant difference between groups. HbA1c decreased significantly in group B (-0.71±0.34%, p<0.001), C (-0.33±0.19%, p=0.030) and D (-0.29±0.18%, p=0.041) compared to group A (0.11±0.08%). Aerobic exercise improved all lipid parameters, while the rest of interventions considerably reduced only triglycerides (p<0.05). Body weight, insulin resistance (HOMA-IR), visfatin were significantly decreased in all active groups (p<0.05). Among groups the most pronounced amelioration of visfatin (-5.65±3.8ng/ml), ghrelin (3.74±1.52ng/ml), and VO2peak (3.12±1.02ml kg-1 min-1) was observed in group B compared to A, C and D groups (p<0.05). Besides, ghrelin was significantly increased in physical activity group D compared to groups A and C (p<0.05). CONCLUSIONS: Daytime physical activity, aerobic and resistance training are positively related to better cardiovascular risk profile in diabetic patients. Among those exercise modalities, supervised aerobic training seems to confer better anti-inflammatory results. NPE Kadoglou was granted by Alexander Onassis Public Benefit Foundation.

Adipokines in Patients With Cancer Anorexia and Cachexia

BackgroundAnorexia, cachexia, and insulin resistance are commonly seen in patients with cancer. Adipocyte-derived hormones or adipokines play a role in the regulation of appetite, body weight, and insulin sensitivity. However,...

Serum Levels of Adipokines in Patients with Chronic HCV Infection: Relationship with Steatosis and Fibrosis

Hepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection. We examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4+/-5kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2+/-3kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA. HCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1a in two patients (3.9%), 1c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders. Patients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group.

Adipokines and Systemic Lupus Erythematosus: Relationship with Metabolic Syndrome and Cardiovascular Disease Risk Factors

To study concentrations of adipokines in patients with systemic lupus erythematosus (SLE) and the relationship among adipokines, the metabolic syndrome (MeS), and cardiovascular disease (CVD) risk factors. We enrolled 50 SLE patients and 26 controls, all women. Leptin, resistin, visfatin, and adiponectin were measured by commercial ELISA kits. MeS prevalence was increased among subjects with SLE. Leptin levels were higher in patients with SLE than controls. Among SLE patients, independent determinants of leptin were insulin levels (p < 0.0001), triglycerides (p = 0.03), body mass index (p = 0.02), corticosteroid dosage (p = 0.02), and SLE Disease Activity Index (p = 0.005). Other adipokines did not differ between SLE patients and controls. Leptin was increased in SLE patients and could play a role in SLE-related cardiovascular diseases.

Plasma adiponectin and resistin levels as predictors of mortality in patients with acute myocardial infarction: data from infarction prognosis study registry

Adiponectin and resistin, which have counteracting effects, are suggested to be associated with inflammation and atherosclerosis. The relationship between their levels and prognosis in high risk patients is, however, still unclear. The aim of this study was to evaluate the prognostic values of these adipokines in patients with acute myocardial infarction (MI). Adiponectin and resistin levels were measured at acute phase of MI in 397 consecutive patients. All patients were followed-up for the occurrence of all-cause and cardiovascular mortalities. Predictors for all-cause and cardiovascular mortalities were analyzed by Cox proportional hazard model. During the mean follow-up period of 12 months, 28 (7.1%) patients died. Unadjusted all-cause mortality rate was significantly higher in patients with high tertiles of adiponectin (P=0.002) and resistin (P=0.002) levels. After controlling of clinical and laboratory variables, age [95% confidence interval (CI): 1.20-2.83, P=0.006], adiponectin (95% CI: 1.01-1.22, P=0.040), resistin (95% CI: 1.06-2.33, P=0.025), and statin use (95% CI: 0.15-0.83, P=0.017) were found to be independent predictors of all-cause mortality. For cardiovascular mortality, only age (95% CI: 1.33-3.25, P=0.001) and renal insufficiency (95% CI: 1.52-12.22, P=0.006) were independent predictors. High plasma adiponectin and resistin levels were predictors for all-cause mortality independent of other risk factors in patients with acute MI. These results confirmed and extended the positive correlations between these adipokines and mortality to a population consisting exclusively of MI.

Metabolic Syndrome

Metabolic Syndrome

Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin‐18 is an independent factor for the improvement of homeostasis model assessment‐beta in type 2 diabetes mellitus

We examined the individual pharmacological effects of the addition of rosiglitazone and metformin to glimepiride on inflammatory markers and adipokines in patients with type 2 diabetes mellitus. We analysed the relationships between these variables, the measurements of insulin sensitivity and beta-cell function in patients treated with rosiglitazone plus glimepiride. One hundred twenty (120) patients with type 2 diabetes mellitus were randomized and treated with glimepiride plus rosiglitazone or glimepiride plus metformin for 12 weeks. The plasma concentrations of the inflammatory markers and adipokines were measured at baseline and after 12 weeks. Markers of insulin sensitivity and beta-cell function were determined by the quantitative insulin sensitivity check index (QUICKI) and the homeostasis model assessment of beta-cell function (HOMA-beta), respectively. Plasma concentrations of adiponectin were measured by radioimmunoassay. Plasma concentrations of resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-18 (IL-18) were measured using ELISA. Improvements in fasting insulin level, QUICKI and HOMA-beta were noted in the rosiglitazone-treated group. Only the QUICKI value improved in the metformin-treated group. Adiponectin concentrations significantly increased in the rosiglitazone-treated group after 12 weeks. Significant decreases in resistin, C-reactive protein, TNF-alpha, IL-6 and IL-18 were seen in the rosiglitazone-treated patients but not in the metformin-treated patients. The independent risk factor for the HOMA-beta change according to stepwise multivariate regression analysis was a change in IL-18. Rosiglitazone, but not metformin, improved the plasma concentrations of inflammatory markers and adipokines in patients with type 2 diabetes mellitus. A decrease in IL-18 is an independent factor for the improvement of HOMA-beta in type 2 diabetes mellitus.

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 +/- 2.7 versus 2.9 +/- 2.2 muU/ml x mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-alpha, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 +/- 16 versus 92 +/- 14 mg/dl; P < 0.05), insulin (23.1 +/- 8.8 versus 19.9 +/- 9; P < 0.05), HOMA index (6.0 +/- 2.7 versus 4.7 +/- 2.8; P < 0.05), and glycated hemoglobin (5.33 +/- 0.58 versus 4.85 +/- 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 +/- 100 versus 370 +/- 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.

Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo

To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance (P = 0.01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes (P = 0.05) and group P had the highest levels of fasting serum cortisol (P = 0.05), nonesterified fatty acids (NEFA; P = 0.06) and C-reactive protein (CRP; P = 0.01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.