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Biomedical subjects

Wifredo Ricart

Publications and source records attributed to Wifredo Ricart.

At least 19 recordsLinked to original sources
PubMed2007

Burden of infection and fat mass in healthy middle-aged men.

OBJECTIVE: Our aim was to study the effect of exposure to four infections on fat mass. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of healthy middle-aged men from the general population (n = 74). Each study subject's serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays (ELISAs). A total pathogen burden score based on these seropositivities [Quantitative Seropositivity Index (QSI)] was constructed. Fat mass was measured by bioelectrical impedance. RESULTS: We observed significant relationships between the HSV-1 titer and fat mass and percentage fat mass. The associations were stronger when considering the infection burden. The QSI was significantly associated with fat mass (r = 0.30, p = 0.009) and percentage fat mass (r = 0.27, p = 0.01). Those subjects in the highest tertile of fat mass showed significantly higher QSI (259.5 +/- 74.1 vs. 206.9 +/- 78.2, p = 0.007). In subjects that were seropositive for Enteroviruses, the relationship between the QSI and fat mass was strengthened (r = 0.51, p = 0.02). In a multivariate regression analysis, the QSI, independently of age and C-reactive protein, contributed to 9% of fat mass variance. DISCUSSION: Pathogen burden showed an association with fat mass. Subjects with increased fat mass could be more susceptible to developing multiple infections resulting in a chronic low-grade inflammation. We can not exclude the possibility that exposure to multiple infections leads to increased fat mass.

Adipose Tissue↗
PubMed2006

An alternatively spliced soluble TNF-alpha receptor is associated with metabolic disorders: a replication study.

In a previous study, we identified a biologically active form of tumor necrosis factor-alpha receptor 2 (sTNFR2) produced by differential splicing (DS-TNFR2) which antagonized TNF-alpha biological activity. Obesity, insulin resistance and type 2 diabetes are linked to increased TNF-alpha action. We hypothesized that subjects with detectable DS-TNFR2 would be protected from developing obesity and related metabolic disorders. Thus, we investigated if circulating DS-TNFR2 concentration was associated with components of the so-called metabolic syndrome among 269 consecutive subjects from the general population. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Plasma DS-TNFR2 concentration was significantly decreased among patients with glucose intolerance or type 2 diabetes mellitus (p=0.026). DS-TNFR2 tended to be associated with fasting and post-load glucose (both r=-0.11, p=0.054), and with diastolic blood pressure in men (r=-0.16, p=0.07). Serum DS-TNFR2 concentration was significantly associated with LDL cholesterol (r=-0.28, p=0.002), uric acid (r=-0.13, p=0.04) and with blood glycated hemoglobin (r=-0.13, p=0.04). DS-TNFR2 declined with increased number of components of the metabolic syndrome (p=0.03). Those subjects with 2 or more components had significantly decreased circulating DS-TNFR2 levels (0.96+/-2.2 versus 1.7+/-3.2, p=0.033). In summary, the circulating concentration of DS-TNFR2 seems to be inversely linked to metabolic disorders, hinting at a possible anti-inflammatory role.

Adult↗
PubMed2006

Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects.

CONTEXT: Levels of TSH respond to fluctuations in serum free T(4) (fT(4)) but remain in a very narrow individual range. There exists current controversy regarding the upper limit of normal serum TSH values above which treatment should be indicated. OBJECTIVE: We aimed to study whether the individually determined fT(4)-TSH relationship was associated with plasma lipids, insulin sensitivity, and endothelial dysfunction in healthy subjects with strictly normal thyroid function according to recent recommendations (0.3-3.0 mU/liter). DESIGN: This was a cross-sectional study. SETTING: The study consisted of a cohort of healthy men from the general population (n = 221). MAIN OUTCOME MEASURES: Oral glucose tolerance, insulin sensitivity (S(I), minimal model), endothelium-dependent vasodilation (high-resolution ultrasound), and plasma lipids were measured in relation to thyroid function tests. RESULTS: Both serum TSH and fT(4).TSH product were positively associated with fasting and postload insulin concentration and negatively with S(I). After body mass index stratification, these associations were especially significant among lean subjects. Serum TSH and fT(4).TSH product also correlated positively with fasting triglycerides and negatively with high-density lipoprotein cholesterol. In a multiple linear regression analysis, age (P = 0.007) and S(I) (P = 0.02) but not body mass index, fasting triglycerides, or serum high-density lipoprotein concentration contributed independently to 3.7 and 3.3%, respectively, of the variance in fT(4).TSH. Those subjects over the median of fT(4).TSH showed reduced endothelium-dependent vasodilation. CONCLUSIONS: Thyroid function tests are intrinsically linked to variables of insulin resistance and endothelial function. It is possible that underlying factors lead simultaneously to increased serum TSH, insulin resistance, ensuing dyslipidemia, and altered endothelial function even within current normal TSH levels.

Brachial Artery↗
PubMed2006

The tumour necrosis factor (TNF)-alpha-308GA promoter polymorphism is related to prenatal growth and postnatal insulin resistance.

OBJECTIVE: Variation in the tumour necrosis factor gene, (TNF) has been associated with insulin resistance traits. We questioned whether the TNF-308G/A polymorphism is associated with birthweight and insulin resistance in children born small for gestational age (SGA), a patient population known to be at risk for insulin resistance. DESIGN: A cross-sectional, hospital-based study assessing insulin sensitivity in SGA children. PATIENTS: One hundred and ninety-eight school-age children born either SGA (n=90, age 7.4+/- 4.5 years) or appropriate for gestational age (AGA, n=108, age 8.7+/- 4.0 years). MEASUREMENTS: All children were genotyped for the TNF-308G/A polymorphism; a biochemical profile was also performed in prepubertal SGA (n=58) and AGA (n=57) subjects. RESULTS: Genotype frequencies for the TNF-308G/A single nucleotide polymorphisms (SNPs) (GG and GA/AA) differed between SGA and AGA children (86%vs. 72% and 14%vs. 28%, respectively; P=0.025). The GG genotype was associated with lower birthweight and birth length (2747.0+/- 23.3 g vs. 2851.0+/- 45.7 g, P=0.045, and 47.0+/- 0.2 cm vs. 48.2+/- 0.4 cm, P=0.011, respectively) and, in AGA but not in SGA children, with higher systolic blood pressure [103.3 (95% confidence interval (CI) 96.4-110.2) mmHg vs. 92.8 (84.9-100.7) mmHg; P=0.028], higher blood glucose [4.8 (4.7-5.0) mmol/l vs. 4.5 (4.3-4.8) mmol/l; P=0.042] and higher homeostasis model assessment for insulin resistance (HOMA-IR) index [1.4 (1.1-1.7) vs. 0.9 (0.4-1.3); P=0.005]. In multivariate analysis, the TNF-308GG genotype was an independent predictor of HOMA-IR during childhood, explaining 8% of its variance. CONCLUSION: SGA children show increased frequency of the TNF-308G allele, an allele that is associated with prenatal growth and with postnatal insulin resistance. The TNF-308G/A polymorphism may have implications in the growth and metabolic abnormalities that characterise SGA children.

Birth Weight↗
PubMed2006

Polymorphisms in the interleukin-6 receptor gene are associated with body mass index and with characteristics of the metabolic syndrome.

OBJECTIVE: Low-grade inflammation has been related to obesity, insulin resistance and the metabolic syndrome. The Asp358Ala variant and the CA-repeat polymorphism in the interleukin-6 receptor (IL-6R) gene have been reported to be associated with obesity in Pima Indians and Spanish women, respectively. The aim of this study was to investigate the association between these polymorphisms and obesity in a Mediterranean-Caucasian population, and to determine whether this polymorphism was related to the metabolic syndrome as defined by the National Cholesterol Education Program - Adult Treatment Panel III (NCEP/ATP-III) criteria. DESIGN: Cross-sectional. PATIENTS: Three hundred and ninety subjects from the general population. METHODS: The Asp358Ala and CA-repeat polymorphisms were analysed by polymerase chain reaction (PCR) amplification, followed by restriction fragment length polymorphism or capillary electrophoresis, respectively. RESULTS: Both polymorphisms were in strong linkage disequilibrium, Asp358 alleles being associated with 149 CA-repeat alleles (chi2 = 76.275, P < 0.0001). Therefore, only the association of the Asp358Ala variant with obesity and the metabolic syndrome was assessed in the whole series of subjects. Subjects homozygous for Asp358 alleles had statistically higher body mass index (BMI) compared with Ala358 carriers (27.7 +/- 5.41 vs. 26.6 +/- 4.96 kg/m2; P < 0.05). Moreover, the prevalence of the metabolic syndrome was significantly higher in carriers of the Asp358 allele compared with Ala358 homozygotes (12.7%vs. 0.0%; P = 0.01). This relationship remained significant after adjusting for age, insulin resistance, sex and BMI. CONCLUSIONS: The Asp358Ala and CA-repeat polymorphisms in the IL-6R gene are associated with obesity and characteristics of the metabolic syndrome in our population of Mediterranean subjects.

Adult↗
PubMed2006

An alternative spliced variant of circulating soluble tumor necrosis factor-alpha receptor-2 is paradoxically associated with insulin action.

OBJECTIVE: Serum concentrations of soluble tumor necrosis factor-alpha (TNF-alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this circulating DS-TNFR2 is associated with insulin action in humans. DESIGN AND METHODS: Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in monocytes. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Insulin sensitivity was measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model of assessment (HOMA) value in a replication study of 223 subjects. RESULTS: Real time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy subjects. A significant and positive association was found between serum DS-TNFR2 concentration and insulin sensitivity (P = 0.032, n = 76). This association was most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002). The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than those with undetectable DS-TNFR2 (42.12+/-22.08 vs 31.71+/- 16.95 micromol x kg(-1) x min(-1), P = 0.039). DS-TNFR2 was inversely associated with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting serum glucose, serum triglycerides and serum uric acid concentration and with the HOMA value (P = 0.03) in the replication study. Circulating DS-TNFR2 declined with increased number of components of the metabolic syndrome. CONCLUSION: Native sTNFR2 and DS-TNFR2 show opposite associations with insulin action. DS-TNFR2 might play a role as a counterpart of the proinflammatory environment associated with insulin resistance.

Adult↗
PubMed2006

The ACAA-insertion/deletion polymorphism at the 3' UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance.

OBJECTIVE: The IGF-II receptor gene (IGFIIR) is located at chromosome 6q26, a region that harbors a genetic marker linked to insulin-resistant traits in Mexican-Americans. In the present study conducted in Spaniards, we tested a common polymorphism in IGFIIR for association with type 2 diabetes and insulin-resistant traits. DESIGN: Case-control association study. METHODS: One hundred and forty-five type 2 diabetic patients and 217 non-diabetic controls were genotyped for the ACAA-insertion/deletion polymorphism at the 3' UTR of IGFIIR. Phenotyping included anthropometrics and a metabolic profile, including serum lipid levels and surrogate indexes of insulin resistance whenever possible. RESULTS: Diabetic patients were more frequently homozygous for the wild type 144 bp allele of IGFIIR compared with controls (diabetic patients 77.2%, controls 51.6%, P<0.001) suggesting a potential protective role against type 2 diabetes for the IGFIIR 140 bp variant. Carrying 140 bp alleles was associated with an odds ratio of having diabetes of 0.290 (95% confidence interval 0.109-0.770), and controls homozygous for the wild type 144 bp allele presented with lower insulin and triglyceride levels, which are proxies for insulin resistance. CONCLUSIONS: The ACAA-insertion/deletion polymorphism at the 3' UTR of IGFIIR is associated with type 2 diabetes and influences surrogate markers of insulin resistance in non-diabetic subjects.

3' Untranslated Regions↗
PubMed2006

Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25).

IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling. We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans. To this aim, a cross-sectional study was conducted in 113 nondiabetic and 43 type 2 diabetic men. Insulin sensitivity (insulin sensitivity index [S(i)] from intravenous glucose tolerance tests in nondiabetic subjects, or the rate constant for disappearance of glucose [K(ITT)] from insulin tolerance tests in type 2 diabetic subjects), circulating IGFBP-rP1 (from enzyme-linked immunosorbent assay), adiponectin (from radioimmunoassay), C-reactive protein (CRP; from immunoturbidimetry), soluble tumor necrosis factor receptor 2 (sTNFR2; from enzyme-amplified sensitivity immunoassay), and IGF system parameters (IGF-I, free IGF-I, and IGFBP-1 from immunoradiometric assay) were assessed in all subjects. Among nondiabetic men, those in the highest quartile for circulating IGFBP-rP1 exhibited decreased S(i) and adiponectin (both P < 0.01) as well as increased CRP and sTNFR2 (both P < 0.05). Circulating IGFBP-rP1 was also found to be increased in previously undiagnosed type 2 diabetic patients (P = 0.01) but not in known type 2 diabetic patients receiving pharmacological therapy. Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively. In additional multivariate analyses, S(i), sTNFR2, and age stood as independent predictive variables of IGFBP-rP1 (together explaining 18% of its variance) in nondiabetic subjects, and BMI became the only independent predictive variable of IGFBP-rP1 (explaining 26% of its variance) in type 2 diabetic men. These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans.

Adiponectin↗
PubMed2006

Serum visfatin increases with progressive beta-cell deterioration.

Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (beta = -0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16-21] vs. 15 ng/ml [13-17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA1c (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34-40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive beta-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration.

Adult↗
PubMed2006

Burden of infection and insulin resistance in healthy middle-aged men.

OBJECTIVE: We hypothesized that burden of infection could be associated with chronic low-grade inflammation, resulting in insulin resistance. We aimed to study the effect of exposure to four infections on insulin sensitivity in apparently healthy middle-aged men (n = 124). RESEARCH DESIGN AND METHODS: By inclusion criteria, all subjects were hepatitis C virus antibody seronegative. Each study subject's serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays. Insulin sensitivity was evaluated using minimal model analysis. RESULTS: The HSV-2 titer was negatively associated with insulin sensitivity even after controlling for BMI, age, and C-reactive protein (CRP). The associations were stronger when considering the infection burden. In particular, in those subjects who were seropositive for C. pneumoniae, the relationship between the quantitative seropositivity index (a measure of the exposure to various pathogens) and insulin sensitivity was strengthened (r = -0.50, P < 0.0001). We also observed decreasing mean insulin sensitivity index with increasing seropositivity score in subjects positive for enteroviruses. In the latter, the relationship between insulin sensitivity and seropositivity was especially significant (r = -0.71, P < 0.0001). In a multivariate regression analysis, both BMI and quantitative seropositivity index (7%) independently predicted insulin sensitivity variance in subjects with C. pneumoniae seropositivity. When controlling for CRP, this association was no longer significant. CONCLUSIONS: Pathogen burden showed the strongest association with insulin resistance, especially with enteroviruses and C. pneumoniae seropositivity. We hypothesize that exposure to multiple pathogens could cause a chronic low-grade inflammation, resulting in insulin resistance.

Cost of Illness↗
PubMed2006

Natural antibiotics and insulin sensitivity: the role of bactericidal/permeability-increasing protein.

The innate immune system can immediately respond to microorganism intrusion by helping to prevent further invasion. Bactericidal/permeability-increasing protein (BPI) is a major constituent of neutrophils that possesses anti-inflammatory properties. Inflammation is increasingly recognized as a component of the metabolic syndrome. We hypothesized that the production of BPI could be linked to insulin sensitivity and glucose tolerance. We studied circulating BPI across categories of glucose tolerance. We also studied whether these cross-sectional associations were of functional importance. For this reason, we investigated circulating bioactive lipopolysaccharide and the effects of changing insulin action-after treatment with an insulin sensitizer (metformin)-on circulating BPI in subjects with glucose intolerance. Finally, we tested whether a 3'-untranslated region (UTR) BPI polymorphism led to differences in BPI and insulin action among nondiabetic subjects. Age- and BMI-adjusted circulating BPI was significantly lower among patients with type 2 diabetes. Circulating BPI correlated negatively with fasting and postload glucose and insulin concentrations. In subjects with glucose intolerance, BPI was also linked to BMI, waist-to-hip ratio, and age- and BMI-adjusted insulin sensitivity. Bioactive lipopolysaccharide was negatively correlated with circulating BPI (r = -0.57, P < 0.0001) and positively with plasma lipopolysaccharide-binding protein (r = 0.54, P = 0.002). In parallel to improved insulin sensitivity, plasma BPI significantly increased in the metformin group but not in the placebo group. A 3'-UTR BPI polymorphism was simultaneously associated with plasma BPI concentration, waist-to-hip ratio, fasting and postload insulin concentration, fasting plasma triglycerides, and insulin sensitivity. These findings suggest that this component of the innate immune system is associated with metabolic pathways.

Adult↗
PubMed2005

[Factors influencing incipient diabetic nephropathy: ESODIAH study].

BACKGROUND AND OBJECTIVE: High cholesterol levels might contribute to the presence of albuminuria. The objective of our study was to evaluate the influence of lipid levels on the development of incipient diabetic nephropathy. Secondary objectives were to evaluate the effects of diabetes control, high blood pressure, age, sex, years of diabetes evolution, body mass index and smoking. PATIENTS AND METHOD: 930 subjects were enrolled in an open observational prospective cohort study of subjects with type 2 diabetes mellitus and high cholesterol levels (ESODIAH study) for 2 years. In our nephropathy study we selected 590 patients who had albuminuria measurements done. In every 4-month interval visit we made a clinical evaluation and blood analysis including HbA1c, lipid profile and microalbuminuria. Statistical analysis included t-Student, chi2 test, and binary logistic regressions. RESULTS: 51.7% men, aged 62.08 years of age and with an evolution of their diabetes of 8.49 years were studied. 40.6% had microalbuminuria and 59.4% had normoalbuminuria. High HbA1c correlated with the presence of albuminuria (odds ratio [OR] = 1.3; 95% confidence interval [CI], 1.12-1.55; p = 0.001). The development of microalbuminuria was more frequent in younger (OR = 0.93; 95% CI, 0.89-0.98), smoker (OR = 3.19; 95% CI, 1.02-9.96), subjects with high systolic blood pressure (OR = 1.02; 95% CI, 1-1.05). Total cholesterol levels at the end of the study were higher in new microalbuminuric (group I) than normoalbuminuric patients (group II) (group I: 211.08 [34.75] mg/dl vs group II: 200.67 [30.50]; p = 0.042). CONCLUSIONS: Tobacco, blood pressure and diabetes control influences the presence and development of microalbuminuria. More studies are required to study the influence of hypercholesterolemia.

Aged↗
PubMed2005

Circulating adiponectin and plasma fatty acid profile.

BACKGROUND: The amount and type of fat in the diet influence the development of obesity and related inflammatory activity. Knowledge of the possible influence of dietary habits on circulating adiponectin, a molecule with putative antiinflammatory properties, may be helpful in preventing atherosclerosis and type 2 diabetes. METHODS: The association between dietary fat, as inferred from plasma fatty acid composition (gas-liquid chromatography), and circulating adiponectin (RIA) was evaluated in 116 healthy individuals. RESULTS: The proportion of saturated fatty acids in plasma was significantly associated with circulating adiponectin concentration (r = -0.24; P = 0.01). Specifically, percentage of palmitic acid (C16:0) was significantly associated with lower adiponectin concentration (r = -0.28; P = 0.002), particularly among women (r = -0.37; P = 0.02) and nonsmokers (r = -0.30; P = 0.007). Percentage of myristic acid (C14:0) was also significantly associated with lower adiponectin among nonsmokers (r = -0.26; P = 0.02) and women (r = -0.39; P = 0.01). The other fatty acids were not significantly associated with adiponectin except for eicosanoic acid (C20:1 omega-9), which was significantly and positively associated with adiponectin in all individuals (r = 0.23; P = 0.01). This latter association was most significant in smokers (r = 0.43; P = 0.007). In a multivariate regression analysis to predict circulating adiponectin, after controlling for age, body mass index, waist-to-hip ratio, and the individual remaining fatty acids, the percentages of palmitic (P = 0.005) and eicosanoic acid (P = 0.03) contributed independently (6% and 3%, respectively) to adiponectin variance. Among nonsmokers, the percentages of palmitic acid (P = 0.01) and omega-3 fatty acids contributed 8% and 7%, respectively, to adiponectin variance. Among smokers, the percentage of eicosanoic acid (P = 0.03) contributed to 10% of adiponectin variance, independently of body mass index, age, waist-to hip ratio, and the remaining individual fatty acids. CONCLUSIONS: Saturated and omega-3 fatty acids of dietary origin (as inferred from plasma fatty acid concentration) are associated with circulating adiponectin concentrations in healthy humans. The proportion of eicosanoic acid also appears to be positively associated with circulating adiponectin. The knowledge of how these interactions occur may be helpful in the planning of dietary measures aimed at the modulation of inflammatory activity.

Adiponectin↗
PubMed2005

Dyslipidemia and inflammation: an evolutionary conserved mechanism.

Inflammation leads to changes in lipid metabolism aimed at decreasing the toxicity of a variety of harmful agents and tissue repair by redistributing nutrients to cells involved in host defence. Acute phase response, mediated by cytokines, preserves the host from acute injury. When this inflammation becomes chronic, it might lead to chronic disorders as atherosclerosis and the metabolic syndrome. The activation of the inflammatory cascade will induce a decrease in HDL-cholesterol (HDL-C), with impairment in reverse cholesterol transport, and parallel changes in apolipoproteins, enzymes, anti-oxidant capacity and ATP binding cassette A1-dependent efflux. This decrease in HDL-C and phospholipids could stimulate compensatory changes, as synthesis and accumulation of phospholipid-rich VLDL which binds bacterial products and other toxic substances, resulting in hypertriglyceridemia. The final consequence is an increased accumulation of cholesterol in cells. When the compensatory response (inflammation) is not able to repair injury, it turns into a harmful reaction, and the lipid changes will become chronic, either by repeated or overwhelming stimulus, enhancing the formation of atherosclerotic lesions. Thus, the classical lipid changes associated with the metabolic syndrome (increased triglycerides and decreased HDL-C) may be envisioned as a highly conserved evolutionary response aimed at tissue repair. Under this assumption, the problem is not the response but the persistence of the stimulus.

Acute-Phase Reaction↗
PubMed2005

Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women.

Inflammatory pathways are increasingly recognized to be tightly associated with insulin resistance in humans. The promoter region of the adiponectin gene--Apm1--encompasses consensus sequences for glucocorticosteroid receptor responsive element. Dexamethasone induced downregulation of adiponectin secretion in vitro, whereas prednisolone administration increased circulating adiponectin concentrations. As previous studies have demonstrated an inverse relationship between corticosteroid-binding globulin (CBG), body mass index, and insulin resistance, we studied whether CBG could explain cortisol-to-adiponectin relationship. One hundred twenty-two healthy subjects were enrolled in a cross-sectional study. Plasma CBG and serum cortisol concentration were measured by radioimmunoassay. The cortisol-to-CBG ratio was used to calculate free cortisol. An RIA kit (Linco Research, St Louis, MO) was used to measure adiponectin levels. Insulin resistance was calculated using the homeostatis model of assessment (HOMA) value. Circulating adiponectin was associated with serum CBG ( r = 0.38, P < .00001), both in men ( r = 0.26, P = .03, n = 79) and women ( r = 0.48, P = .003, n = 43), and with insulin resistance (HOMA index) ( r = -0.30, P < .0001) in both. Free cortisol correlated negatively with adiponectin only in women ( r = -0.32, P = .04), but not in men ( r = 0.01, P = .89). Serum CBG concentration was significantly lower among men in the lowest quartile of adiponectin when compared with the remaining subjects (37.3 +/- 5.7 vs 40.6 +/- 5.1, P = .016), whereas men in the highest quartile of adiponectin showed significantly increased free cortisol index (14.2 +/- 3.3 vs 12.2 +/- 3.1, P = .039). Women in the lowest quartile of adiponectin also displayed significantly lower CBG concentration than that present in the remaining subjects (38.6 +/- 6.9 vs 44.4 +/- 5.5, P = .016), whereas free cortisol index was not significantly different across adiponectin quartiles ( P = .1). In a stepwise regression analysis, body mass index ( P = .0011), CBG ( P = .0047), and sex ( P = .04) contributed to 15%, 8%, and 3%, respectively, of adiponectin variance. Using CBG as dependent variable, both adiponectin ( P = .0002) and fasting cortisol ( P = .019) contributed to 14% and 4%, respectively, of CBG variance. In summary, circulating adiponectin, CBG concentration, and fasting cortisol were significantly interrelated in healthy subjects. A significant sexual dimorphism exists in this association.

Adiponectin↗
PubMed2005

Potential role of interleukin-18 in liver disease associated with insulin resistance.

OBJECTIVE: Interleukin (IL)-18 has been associated with obesity and insulin resistance, both risk factors for the development of liver disease, but the role of IL-18 in liver disease associated with insulin resistance is presently unknown. We hypothesized that circulating IL-18 would be related to serum concentrations of liver chemistry tests (LCTs) in apparently healthy subjects and wished to study whether this correlation was dependent on insulin sensitivity (S(I)). RESEARCH METHODS AND PROCEDURES: One hundred six apparently healthy white men consecutively enrolled in a cross-sectional, population-based study dealing with S(I) in men were studied, and S(I) (minimal model analysis), LCTs (colorimetry), and IL-18 serum concentrations (immunoassay) were assessed. RESULTS: Compared with subjects in the lowest quartile for serum IL-18, subjects in the highest quartile exhibited increased serum triglycerides and decreased S(I), in addition to higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (all p < 0.05). The direct association between both ALT and AST and IL-18 was further confirmed by examining the distribution of serum IL-18 by quartiles of ALT and AST. Subjects in the highest quartile for serum ALT and AST had higher IL-18 concentrations compared with subjects in the lowest quartile for these LCTs (both p = 0.01). In multiple regression analysis, IL-18, but not S(I), was an independent predictor of serum concentrations of ALT and AST, explaining 7% and 4% of their variance, respectively. DISCUSSION: In summary, IL-18 serum concentrations are associated in apparently healthy humans with plasma concentrations of various LCTs. IL-18 could contribute to the development of liver disease associated with insulin resistance.

Adult↗