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Biomedical subjects

Abel López-Bermejo

Publications and source records attributed to Abel López-Bermejo.

At least 19 recordsLinked to original sources
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

IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies.

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G>C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.

Case-Control Studies↗
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

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↗
PubMed2005

Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects.

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.

Brachial Artery↗
PubMed2005

Iron stores, blood donation, and insulin sensitivity and secretion.

BACKGROUND: Epidemiologists have observed that blood donation is associated with decreased risk of type 2 diabetes and cardiovascular disease. METHODS: We investigated the relationship between iron stores and insulin sensitivity, after controlling for known confounding factors, and compared insulin sensitivity between blood donors and individuals who had never donated blood (nondonors). In 181 men, insulin sensitivity and insulin secretion were evaluated through frequently sampled intravenous glucose tolerance tests with minimal model analysis. Men who donated blood between 6 months and 5 years before inclusion (n = 21) were carefully matched with nondonors (n = 66) for age, body mass index, waist-to-hip ratio, and cardiovascular risk profile, including blood lipids, blood pressure, and smoking status. RESULTS: Frequent blood donors (2-10 donations) had increased insulin sensitivity [3.42 (1.03) vs 2.45 (1.2) x 10(-4) x min(-1) x mIU/L; P = 0.04], decreased insulin secretion [186 (82) vs 401.7 (254) mIU/L x min; P <0.0001], and significantly lower iron stores [serum ferritin, 101.5 (74) vs 162 (100) microg/L; P = 0.017] than nondonors, but the 2 groups had similar blood hematocrits and blood hemoglobin concentrations. CONCLUSIONS: Blood donation is simultaneously associated with increased insulin sensitivity and decreased iron stores. Stored iron seems to impact negatively on insulin action even in healthy people, and not just in classic pathologic conditions associated with iron overload (hemochromatosis and hemosiderosis). According to these observations, it is imperative that a definition of excessive iron stores in healthy people be formulated.

Adult↗
PubMed2004

An inflammation score is better associated with basal than stimulated surrogate indexes of insulin resistance.

Most studies describe the association between one particular inflammatory marker and insulin resistance (IR), features of the metabolic syndrome, or progression to type 2 diabetes. We aimed to build an Inflammation Score as a tool to measure IR-associated inflammatory activity and to evaluate the ability of different surrogate indexes of IR to reflect the inflammatory state. We studied 81 subjects, aged 47.7 +/- 12 yr with a body mass index of 28.3 +/- 4 kg/m(2). The Inflammation Score was composed of: white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and soluble fraction of TNF-alpha receptors 1 and 2. All the subjects underwent a frequently sampled iv glucose tolerance test, an oral glucose tolerance test, and surrogate indexes of IR were calculated. Each increase in the Inflammation Score was associated with a progressive increase in IR. We found significant differences across categories (0-1, 2, 3, and 4-5 points in the score) in age (P = 0.048), waist circumference (P = 0.015), body mass index (P = 0.013), blood pressure (P = 0.005), and uric acid (P = 0.031). The Inflammation Score was significantly associated with all but three of the surrogate IR indexes [2-h insulin glucose ratio, Gutt's insulin sensitivity (SI) index, and Avignon's 2-h SI index]. Surrogate indexes obtained from basal values showed a similar correlation with the Inflammation Score than the SI from frequently sampled iv glucose tolerance test. In summary, the Inflammation Score is a useful tool in the evaluation of IR-associated inflammatory activity. The surrogate indexes obtained using fasting glucose and insulin appear to better reflect this inflammatory state. Basal rather than stimulated indexes should be used in the evaluation of therapeutic measures aimed at modifying IR-associated inflammatory activity.

Adult↗
PubMed2004

Adiponectin, hepatocellular dysfunction and insulin sensitivity.

OBJECTIVE: Insulin resistance plays a major aetiological role in the development of fatty liver disease. Because adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumour necrosis factor, a cytokine known to induce insulin resistance and liver damage, we wished to study whether low circulating adiponectin would be associated with higher serum concentrations of liver enzymes in healthy subjects. DESIGN: Cross-sectional, population-based study dealing with diabetes prevalence in northern Spain. PATIENTS: Two hundred and fifty-seven apparently healthy Caucasian subjects consecutively enrolled in the study. MEASUREMENTS: Adiponectin serum levels were measured by enzyme-linked immunosorbent assay (ELISA), liver function tests (LFTs) by colourimetry and insulin resistance by the homeostasis model of assessment (HOMA value). RESULTS: Adiponectin levels were negatively correlated with alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT), before and after adjustment for sex, age, body mass index (BMI) and insulin resistance (ALT; r = -0.32, P < 0.001; adjusted: r = -0.13, P = 0.033; GGT; r = -0.31, P < 0.001; adjusted: r = -0.16, P = 0.011). Additionally, adiponectin correlated with alkaline phosphate (ALKP) only after adjusting for the same confounding variables (r =-0.10, P = 0.098; adjusted: r = -0.14, P = 0.031). A general linear model, adjusting for age, sex and BMI, was constructed to predict the decrease in circulating adiponectin for each LFT value (i.e. ALT, GGT and ALKP) above the median. Beyond one LFT value above the median, serum adiponectin decreased by -0.97 mg/l (95% CI -1.46 to -0.48). In multiple regression analysis, sex, BMI and adiponectin, but not insulin resistance, predicted serum concentrations of both ALT and GGT, explaining 19% and 14% of their variance, respectively. Age, BMI and adiponectin, but not sex or insulin resistance, explained 20% of ALKP variance. CONCLUSIONS: Adiponectin levels are associated in healthy humans with plasma concentrations of various liver function tests. The contributions of adiponectin to maintaining liver integrity through the regulation of both insulin sensitivity and/or the inflammatory response merit further studies.

Adiponectin↗