Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population-based study

BACKGROUND: We evaluated the relationship of insulin sensitivity (assessed with the quantitative insulin sensitivity check index, QUICKI) to adiponectin and pro-inflammatory markers, levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-1 receptor antagonist (IL-1 Ra). METHODS: Cross-sectional study. Study population (N=923, i.e 411 men and 512 women) included five different population-based age groups (born in 1942, 1947, 1952, 1957 and 1962), [mean age 46 years and mean body mass index (BMI) 26 kg/m(2)]. Study protocol included an interview and measurements of anthropometric parameters and glucose, insulin, adiponectin, hs-CRP and IL-1 Ra. RESULTS: Correlation (r) between QUICKI and adiponectin level was 0.334 [95% confidence intervals (CI), 0.275-0.392] and partial correlation adjusted for gender, BMI, smoking status, physical activity and age was 0.247 (95% CI, 0.185-0.308). There was negative correlation between QUICKI and IL-1 Ra (r= -0.385; 95% CI, -0.440 to -0.328) which remained statistically significant after the adjustment for confounding factors (r= -0.178; 95% CI, -0.240 to -0.113). Similarly, QUICKI was negatively correlated with hs-CRP (r= -0.241; 95% CI, -0.302 to -0.178), but after the adjustment it lost its statistical significance. There was a statistically significant gender difference (p=0.018) in correlation between QUICKI and IL-1 Ra levels (men: r= -0.348; 95% CI, -0.436 to - 0.261; women r= -0.500; 95% CI, -0.537 to -0.398). CONCLUSIONS: Our results show that adiponectin level and markers of low-grade inflammation are related to insulin sensitivity. Adiponectin and IL-1 Ra levels might be better markers of the risk of obesity and type 2 diabetes than hs-CRP.     

The metabolic syndrome and high C-reactive protein: prevalence and differences by sex in a southern-European population-based cohort

BACKGROUND: To evaluate the prevalence of the metabolic syndrome (MS) and its components in a population-based cohort, and to analyse the association between gender, environmental conditions, C-reactive protein (CRP), and the syndrome. METHODS: Out of 1877 subjects aged 45-64, who represented all the patients of six family physicians, representative of the sanitary districts of Asti (north-western Italy), 88% accepted to participate in an interview on personal habits, and several clinical and laboratory measurements. RESULTS: The MS (National Cholesterol Education Program criteria) was present in 24% of males and 22% of females. Males had a significantly higher percentage of hyperglycaemia, hypertension, hypertriglyceridemia, whereas females had a higher prevalence of central obesity and low HDL-cholesterol. In a multiple logistic regression model, the MS was significantly associated with increasing age, BMI, and >30 g/day alcohol intake (OR = 1.42; 95% CI 1.27-1.58), and negatively to higher education level (OR = 0.52; 95% CI 0.28-0.99) and moderate exercise (OR = 0.65; 95% CI 0.57-0.76). CRP levels are highly correlated to BMI and the components of the syndrome. The association between CRP and the MS remains significant in women only, in a multivariate analysis, after multiple adjustments (OR = 1.73; 95% CI 1.42-2.11). Higher CRP levels, correlated to smoking and, inversely, to alcohol intake, identify a further 12% of the cohort at higher cardiovascular risk. CONCLUSIONS: The MS affects more than 20% of this middle-aged cohort, but more than 30%, with higher CRP levels are at high cardiovascular risk. Healthier lifestyle habits are inversely associated with the MS and CRP levels, suggesting the need for strategies and their implementation in the general population.     

Obesity and C‐reactive protein in various populations: a systematic review and meta‐analysis

Obesity has been associated with elevated levels of C‐reactive protein (CRP), a marker of inflammation and predictor of cardiovascular risk. The objective of this systematic review and meta‐analysis was to estimate the associations between obesity and CRP according to sex, ethnicity and age. MEDLINE and EMBASE databases were searched through October 2011. Data from 51 cross‐sectional studies that used body mass index (BMI), waist circumference (WC) or waist‐to‐hip ratio (WHR) as measure of obesity were independently extracted by two reviewers and aggregated using random‐effects models. The Pearson correlation (r) for BMI and ln(CRP) was 0.36 (95% confidence interval [CI], 0.30–0.42) in adults and 0.37 (CI, 0.31–0.43) in children. In adults, r for BMI and ln(CRP) was greater in women than men by 0.24 (CI, 0.09–0.37), and greater in North Americans/Europeans than Asians by 0.15 (CI, 0–0.28), on average. In North American/European children, the sex difference in r for BMI and ln(CRP) was 0.01 (CI, ?0.08 to 0.06). Although limited to anthropometric measures, we found similar results when WC and WHR were used in the analyses. Obesity is associated with elevated levels of CRP and the association is stronger in women and North Americans/Europeans. The sex difference only emerges in adulthood.     

C-reactive protein and metabolic syndrome in women with previous gestational diabetes

BACKGROUND: This study evaluates the presence of metabolic syndrome (MS) and its association with C-reactive protein (CRP) and other cardiovascular (CV) risk factors, in a sample of women with and without previous Gestational Diabetes (pGDM). METHODS: One hundred and sixty-six women with pGDM and 98 women (controls) with uncomplicated pregnancy were studied 16 months after delivery. In all women, plasma glucose, insulin, lipid profile, serum uric acid, C-reactive protein, fibrinogen and homocysteine were measured. MS was defined according to NCEP ATPIII criteria. RESULTS: MS was identified in 15 pGDM women (9%) versus 1 control (1%) (p < 0.001). The more frequent metabolic traits were abdominal obesity (36% vs 17%) and low HDL-cholesterol (34% vs 17% in pGDM women and controls, respectively; all p < 0.01). HOMA-R, LDL-cholesterol, fibrinogen, serum uric acid and CRP resulted significantly higher in pGDM women with MS as compared to those without MS after adjustment for BMI. In women with no criteria for MS, only CRP levels were found to be higher in pGDM women compared to controls (p < 0.05). Seventeen percent of pGDM women with no criteria for MS had CRP levels >or=1 mg/L (all controls showed CRP levels <1 mg/L). After a stepwise regression analysis, CRP levels were independently correlated to HOMA-R (r2 = 0.27, p < 0.001) and fibrinogen (r2 = 0.30, p < 0.001). CONCLUSIONS: In our population, MS occurs in a sizable proportion of pGDM women and is associated with increased levels of CRP, fibrinogen, uric acid and LDL-cholesterol. Moreover, higher levels of CRP, a marker of chronic low-grade inflammation, are present in a subset of women with pGDM, independently of MS.     

C‐reactive protein during and after myocardial infarction in relation to cardiac injury and left ventricular function at follow‐up

Background

Acute myocardial infarction (MI) invokes a large inflammatory response, which contributes to myocardial repair.

Hypothesis

We investigated whether C‐reactive protein (CRP) measured during MI vs at 1 month follow‐up improves the prediction of left ventricular (LV) function.

Methods

We prospectively enrolled 131 consecutive patients with acute MI and without non‐cardiovascular causes of inflammation. We correlated admission and peak levels of CRP during hospitalization and high‐sensitivity (hs) CRP at 1 month follow‐up with markers of cardiac injury. Clinical follow‐up and echocardiography for LV function were performed at a mean of 17 months.

Results

Median CRP levels were 1.89 mg/L on admission with MI, peaked to 12.10 mg/L during hospitalization and dropped to 1.24 mg/L at 1 month. Although admission CRP levels only weakly correlated with ejection fraction in the acute phase of MI (coefficient ?0.164, P = 0.094), peak CRP was significantly related to ejection fraction (coefficient ?0.4, P < 0.001), hsTroponin T (0.389, P < 0.001), and white blood cell count (0.389, P < 0.001). hsCRP at 1 month was not related to the extent of acute cardiac injury. These findings were replicated in an independent cohort of 57 patients. Peak CRP predicted LV dysfunction at follow‐up (OR 11.0, 3.1‐39.5 per log CRP, P < 0.001), persisting after adjustment for infarct size (OR 5.1, 1.1‐23.6, P = 0.037), while hsCRP at 1 month was unrelated to LV function at follow‐up.

Conclusions

hsCRP 1 month post‐MI does not relate to acute cardiac injury or LV function at follow‐up, but we confirm that peak CRP is an independent predictor of LV dysfunction at follow‐up.

     

Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes

Abstract. Luotola K, Pietilä A, Zeller T, Moilanen L, Kähönen M, Nieminen MS, Kesäniemi YA, Blankenberg S, Jula A, Perola M, Salomaa V (Helsinki University Hospital, Helsinki; National Institute for Health and Welfare, Helsinki, Finland; University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany; University Hospital of Kuopio, Kuopio; Tampere University Hospital and Medical School, University of Tampere, Tampere; University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu; National Institute for Health and Welfare, Turku; and Institute for Molecular Medicine Finland, Helsinki, Finland). Associations between interleukin‐1 (IL‐1) gene variations or IL‐1 receptor antagonist levels and the development of type 2 diabetes. J Intern Med 2010; 269 : 322–332. Objectives. To examine whether interleukin‐1 receptor antagonist (IL‐1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C‐reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin‐1 (IL‐1) locus would predict clinically incident diabetes. Design. Two observational prospective cohort studies. Setting. Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. Subjects. Random population samples consisting of 5511 subjects aged 30–74 years in Health 2000 and 7374 subjects aged 25–74 years in FINRISK 1997. Results. During follow‐up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL‐1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single‐nucleotide polymorphisms: rs3213448 in IL‐1 receptor antagonist (IL1RN), rs1143634 in IL‐1 beta (IL1B) and rs1800587 in IL‐1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender‐specific associations with the risk of clinically incident diabetes. Conclusions. IL‐1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL‐1 locus may have gender‐specific associations with the risk of type 2 diabetes.     

Correlation of carotid artery atherosclerosis with C-reactive protein and adiponectin in patient with metabolic syndrome

Background Metabolic Syndrome(MS) is a group of conditions included hypertension,hyperlipidemia,central obesity,impaired glucose tolerance and insulin resistance,which may contribute to risk factors for atherosclerosis syndrome.Insulin resistance is the core mechanism? while the underlying mechanism is not clear.This article aims to study the correlation of carotid atherosclerosis with C-reactive protein and adiponectin in metabolic syndrome(MS) patients.Methods According to bilateral carotid artery atherosclerosis echocardiography,226 patients with metabolic syndrome were randomized to three groups,of which were non-carotid atherosclerosis plaque group(MS-1 group,n = 94),carotid artery atherosclerosis plaque group(MS-2 group,n = 132),and normal control group(n = 36).Determination of serum insulin,high sensitivity C-reactive protein,adiponectin and bilateral carotid artery atherosclerosis ultrasonography and other indicators,semi-quantitative estimates of the extent and severity of plaque.Results ①In two MS groups,carotid artery atherosclerosis,intima-media thickness(IMT),insulin resistance index(HOMA-IR) and high sensitive C-reactive protein(hs-CRP) were significantly higher than the control group(P 0.01),while adiponectin was lower than the control group(P 0.01);When MS-2 group was compared to MS-1 group,there were significant differences(P 0.01).②IMT was positively correlated with HOMA-IR and hs-CRP(P 0.01) while negatively correlated with adiponectin(P 0.01).Conclusions C-reactive protein and adiponectin in MS patients were correlated with carotid atherosclerosis and insulin resistance,which may be used as the assessment of MS patients.     

Calcitonin therapy in postmenopausal osteoporosis: effects on serum levels of interleukin‐1, interleukin‐6 and tumor necrosis factor‐α

Background: It has been suggested that the effects of calcitonin (CT) therapy for senile and postmenopausal osteoporosis were due to its modulatory effects on bone‐related cytokines. A significantly increased release of IL‐1, IL‐6 and TNF‐α, which have bone resorptive effects, has been reported in osteoporotic patients. Aim: In this study we investigated the effects of CT therapy on the levels of IL‐1, IL‐6 and TNF‐α. Method: Forty postmenopausal osteoporotic women were included to the study. The first group consisting of 20 patients were given 100 IU CT subcutaneously and 1000 mg elemental calcium for 15 consecutive days. The second group or the control group also consisting of 20 patients were only given 1000 mg elemental calcium and both of the groups were not allowed to take any other medication. Results: In the first group the mean serum TNF‐α level significantly decreased from 16.9 ± 24.2 pg/mL to 8.6 ± 13 pg/mL after 1500 IU CT therapy (P < 0.05). The control group's mean serum level of IL‐1, IL‐6 and TNF‐α did not reveal any statistically significant differences (P > 0.05). Conclusion: Our results suggest that CT therapy for osteoporosis may partially be due to its inhibitory effects on TNF‐α, and probably IL‐1. However, further in‐vitro and ex‐vivo studies are needed to clarify this hypothesis.     

Intra‐individual association between C‐reactive protein and insulin administration in postoperative lumbar spinal canal stenosis patients: A retrospective cohort study

The association of intra‐individual variability in insulin requirements with C‐reactive protein levels among acute phase patients remains unclear. This retrospective cohort study aimed to evaluate this association. Patients with type 2 diabetes undergoing surgery for lumbar spinal canal stenosis were included in the study. We analyzed 286 records of 49 patients using the linear mixed effects model. The model showed C‐reactive protein levels to be significantly associated with insulin requirements, with an effect size of 0.60 U/day for an elevation of 1 mg/dL. The effect size was increased in patients with higher hemoglobin A1c levels. Our findings imply that C‐reactive protein levels could be a useful clinical biomarker when blood glucose levels are controlled in acute phase patients.     

Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population‐based study

Abstract. Schiopu A, Hedblad B, Engström G, Struck J, Morgenthaler NG, Melander O (Lund University, Skåne University Hospital Malmö, Malmö, Sweden; BRAHMS GmbH/Thermo Fisher Scientific, Hennigsdorf, Germany). Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population‐based study. J Intern Med 2012; 272: 484–491. Objectives: A number of inflammatory biomarkers such as C‐reactive protein (CRP) are independent predictors of cardiovascular risk. The inflammatory biomarker procalcitonin (PCT) has previously been shown to be associated with coronary atherosclerosis and the metabolic syndrome. We evaluated the ability of PCT to predict future cardiovascular events in a population of apparently healthy individuals. Design: We measured plasma PCT levels in 3713 subjects with no previous history of cardiovascular disease, randomly selected from the Malmö Diet and Cancer cohort. The correlation between PCT concentration and the incidence of coronary events, stroke and cardiovascular death over a median follow‐up period of 13.7 years was studied using a Cox regression analysis corrected for age, sex, CRP level, traditional risk factors and renal function. Results: Age and sex were strong determinants of PCT; the concentration of PCT was significantly higher in men than in women. PCT was associated with several of the established cardiovascular risk factors (CRP, hypertension, diabetes and renal function) as determined by multivariate linear regression. Of note, PCT was inversely correlated with HDL and smoking. We found significant correlations between PCT levels, coronary events and cardiovascular death. However, these relationships lost statistical significance when the analysis was corrected for CRP and the traditional risk factors. Conclusions: This is the largest population‐based prospective study to demonstrate a positive association between plasma PCT levels and cardiovascular risk in subjects with no previous history of acute cardiovascular events. However, the high degree of covariation between PCT and other cardiovascular risk factors limits the value of PCT as an independent cardiovascular risk predictor.     

Association between C‐reactive protein and pre‐diabetic status in a Chinese Han clinical population

Background C‐reactive protein (CRP) has been showed to be associated with type 2 diabetes mellitus, but whether CRP underlies glucose disorders in Asian people is still unclear, for they have much lower body mass index (BMI) levels than these Westerns in previous studies. Method In this clinical‐based cross‐sectional study, the association between CRP and hyperglycaemia in different BMI levels and different gender was compared among 1730 Chinese Han men and women, including 1258 subjects with normal glucose tolerance (NGT), 126 subjects with impaired fasting glucose (IFG) and 346 subjects with impaired glucose tolerance (IGT). Subjects with isolated IFG or IGT were all newly diagnosed and did not use anti‐diabetic drugs. Results Compared with subjects with NGT, BMI, fasting blood glucose, homoeostatis model assessment insulin resistance (HOMA‐IR), blood pressure, dyslipidemia, and serum CRP levels were increased in subjects with IGT and IFG. In stratified analyses, increasing CRP levels were strongly associated with prevalence of IGT and IFG in different BMI strata. After adjustment for sex, age, BMI, education, alcohol consumption, smoking, hypertension status, recreational physical activity and occupational physical activity, the ORs across quartiles of CRP were 1.00, 1.43, 2.14 and 2.29 for IFG (P for trend: 0.025) and 1.00, 1.85, 2.32 and 2.79 for IGT (P for trend: 0.012). Conclusion These results support the hypothesis that chronic inflammation may be involved in the development of hyperglycaemia, even though in a thinner and healthy population. Copyright © 2008 John Wiley & Sons, Ltd.