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Biomedical subjects

J M Fernández-Real

Publications and source records attributed to J M Fernández-Real.

At least 19 recordsLinked to original sources
PubMed2006

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin.

AIMS/HYPOTHESIS: Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. MATERIALS AND METHODS: We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model. RESULTS: Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation. CONCLUSIONS/INTERPRETATION: These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

Adult↗
PubMed2006

Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity.

TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.

Adipose Tissue↗
PubMed2005

Body mass index has a greater impact on pregnancy outcomes than gestational hyperglycaemia.

AIMS/HYPOTHESIS: We evaluated diabetes-related pregnancy outcomes in a cohort of Spanish women in relation to their glucose tolerance status, prepregnancy BMI and other predictive variables. METHODS: The present paper is part of a prospective study to evaluate the impact of American Diabetes Association (2000) criteria in the Spanish population. A total of 9,270 pregnant women were studied and categorised as follows according to prepregnancy BMI quartiles and glucose tolerance status: (1) negative screenees; (2) false-positive screenees; (3) gestational diabetes mellitus (GDM) according to American Diabetes Association criteria only; and (4) GDM according to National Diabetes Data Group criteria (NDDG). We evaluated fetal macrosomia, Caesarean section and seven secondary outcomes as diabetes-related pregnancy outcomes. The population-attributable and population-prevented fractions of predictor variables were calculated after binary logistic regression analysis with multiple predictors. RESULTS: Both prepregnancy BMI and abnormal glucose tolerance categories were independent predictors of pregnancy outcomes. The upper quartile of BMI accounted for 23% of macrosomia, 9.4% of Caesarean section, 50% of pregnancy-induced hypertension and 17.6% of large-for-gestational-age newborns. In contrast, NDDG GDM accounted for 3.8% of macrosomia, 9.1% of pregnancy-induced hypertension and 3.4% of preterm births. CONCLUSIONS/INTERPRETATION: In terms of population impact, prepregnancy maternal BMI exhibits a much stronger influence than abnormal blood glucose tolerance on macrosomia, Caesarean section, pregnancy-induced hypertension and large-for-gestational-age newborns.

Adult↗
PubMed2005

Potential impact of American Diabetes Association (2000) criteria for diagnosis of gestational diabetes mellitus in Spain.

AIMS/HYPOTHESIS: This study was carried out to determine the impact of American Diabetes Association (ADA) 2000 criteria for the diagnosis of gestational diabetes mellitus (GDM) in the Spanish population. METHODS: Pregnant women were assigned to one of four categories: negative screenees, false-positive screenees, ADA-only-GDM (untreated) and GDM according to National Diabetes Data Group (NDDG) criteria (treated). Fetal macrosomia and Caesarean section were defined as primary outcomes, with seven additional secondary outcomes. RESULTS: Of 9,270 pregnant women screened for GDM, 819 (8.8%) met NDDG criteria. If the threshold for defining GDM had been lowered to ADA criteria, an additional 2.8% of women would have been defined as having the condition (relative increase of 31.8%). Maternal characteristics of women with ADA-only-GDM were between those of false-positive screenees and women with NDDG-GDM. The risk of diabetes-associated complications was slightly elevated in the individuals who would have been classified as abnormal only after the adoption of ADA criteria. In addition, the ADA-only-GDM contribution to morbidity was lower than that of other variables, especially BMI. CONCLUSIONS/INTERPRETATION: Use of the ADA criteria to identify GDM would result in a 31.8% increase in prevalence compared with NDDG criteria. However, as the contribution of these additionally diagnosed cases to adverse GDM outcomes is not substantial, a change in diagnostic criteria is not warranted in our setting.

Adolescent↗
PubMed2005

Lowering of blood pressure leads to decreased circulating interleukin-6 in hypertensive subjects.

Interleukin-6 (IL-6), the major proinflammatory cytokine, has been described to be associated with the hypertensive and atherosclerotic states. We aimed to explore whether the concentration of circulating IL-6 and adhesion molecules could be modified by decreasing blood pressure in hypertensive subjects. A total of 30 subjects (18 men), aged 34-48 years, were enrolled in this study, 17 hypertensive never-treated patients (HTA) and 13 normotensive subjects (C). HTA subjects were treated with irbesartan, 150-300 mg/day for 3 months, and serum IL-6, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, sP-selectin, sE-selectin and monocyte chemoattractant protein-1 were measured at 0 and 12 weeks. The two study groups were similar in age, body mass index (BMI) and gender. At baseline, circulating IL-6 levels, but not adhesion molecules, were significantly associated with systolic blood pressure (r=0.41; P=0.03) and BMI (r=0.53; P=0.005). Systolic and diastolic blood pressure decreased significantly (P<0.01) in parallel to serum IL-6 levels (from 3.72+/-0.82 to 3.23+/-0.19 pg/ml, P=0.02) reaching a similar concentration to normotensive patients (3.33+/-0.3 pg/ml) after treatment with irbesartan. No significant changes were observed in any other of the tested parameters. In conclusion, the treatment of high blood pressure lowers circulating IL-6 in young hypertensive patients.

Adult↗
PubMed2005

[Prevalence of diabetic retinopathy in the region of Girona. Study of related factors].

PURPOSE: To determine of the prevalence of diabetic retinopathy in the general diabetic population in the Girona region and epidemiologic study of the related factors. METHODS: A population-based cross-sectional study of a randomised sample taken of 401 diabetics in the Girona region. Descriptive statistical analysis of the ocular lesions in relation to diabetic retinopathy and analysis of logistic regression in order to determine the related factors. RESULTS: 30.6% (IC 95%: 26.5-35.5) of the sample presented some degree of diabetic retinopathy, 19.4% (IC 95%: 15.4-24.0) at the initial stage, 8.4% (IC 95%: 5.8-1.9) pre-proliferative and 2.6% (IC 95%: 1.3-5.1) at a proliferative stage. Regarding the type of diabetes, 53% of the patients with type 1 diabetes and 34.2% of those with type 2 diabetes had retinopathy. Retinopathy was observed in 15.7% of diabetics with less than 10 years of diabetes evolution, 51.3% in those between 10 and 20 years and 62.8% in those with more than 20 years. The concentration of HbA1C was significantly associated with the degree of retinopathy. Of those patients with retinopathy, 60.3% were insulin-treated, 30.6% with oral hypoglucemiants and 10.3% on diet only. Patients with family antecedents of retinopathy presented a prevalence three times greater than those without. CONCLUSIONS: Approximately one in three diabetic patients exhibited some degree of retinopathy in this study dealing with a population-based cohort of diabetic patients in Spain. The prevalence was greater among type I diabetic patients. As expected, years of evolution of the disease, type of treatment and diabetic metabolic control were the most significant factors influencing the presence of retinopathy.

Aged↗
PubMed2004

Maternal soluble tumour necrosis factor receptor type 2 (sTNFR2) and adiponectin are both related to blood pressure during gestation and infant's birthweight.

OBJECTIVE: Tumour necrosis factor alpha (TNF-alpha) and adiponectin are strongly related to insulin sensitivity; insulin resistance of pregnancy is a major determinant of infant's birthweight. We aimed to study the contributions of maternal serum concentrations of soluble TNF-alpha receptors (sTNFR1 and sTNFR2) and adiponectin to infant's birthweight. DESIGN: Cross-sectional, hospital-based study of insulin sensitivity during gestation. PATIENTS: Fifty-one healthy women with uncomplicated pregnancy and delivery (except for elective Caesarian section) and their healthy newborn infants. measurements Maternal blood levels of glucose, insulin, glycosylated haemaglobin (HbA1c), sTNFR1, sTNFR2 and adiponectin at delivery; cord-blood levels of sTNFR1, sTNFR2 and adiponectin. RESULTS: At delivery, maternal sTNFR2 correlated with systolic blood pressure (SBP; r = 0.38, P = 0.005). In multiple regression analyses, SBP and HbA1c were independent predictors of sTNFR2, explaining 18 and 7% of its variance, respectively; insulin resistance index (HOMA-IR), body mass index at delivery and SBP were independent predictors of adiponectin, explaining 15, 8 and 7% of its variance, respectively. Both maternal sTNFR2 and SBP were negatively correlated with infant's birthweight (r = -0.28, P = 0.04 and r = -0.36, P = 0.01 respectively, adjusted for sex and gestational age). In multivariate regression analyses, infant's sex and either maternal sTNFR2 or adiponectin were independent predictors of infant's birthweight, each explaining between 6 and 9% of birthweight variance. Further addition of maternal SBP to these models revealed that this variable was the main predictor of infant's birthweight, explaining 13% of its variance. CONCLUSIONS: Maternal sTNFR2 and adiponectin are independently related to both maternal blood pressure and infant's birthweight in uncomplicated pregnancy. The contributions of the TNF-alpha system and adiponectin to hypertensive disorders of pregnancy and fetal growth merit further studies.

Adiponectin↗
PubMed2003

Lower rate of tumor necrosis factor-alpha -863A allele and higher concentration of tumor necrosis factor-alpha receptor 2 in first-degree relatives of subjects with type 2 diabetes.

Allelic variants of the tumor necrosis factor-alpha (TNF-alpha) gene seem to contribute to insulin resistance increasing the transcription rate of TNF-alpha. The TNF-alpha -863A allele is associated with a lower expression of TNF-alpha gene and less secretion of the cytokine. To investigate whether an abnormal TNF-alpha system regulation may contribute to early impairment of insulin action in first-degree relatives of patients with type 2 diabetes mellitus (DM), we studied the TNF-alpha -863C/A polymorphism and the soluble fraction of TNF-alpha receptor-2 (sTNFR2) concentration in these subjects in comparison to a control group. A total of 52% of subjects in the relatives' group showed an abnormal oral glucose tolerance (either as impaired glucose tolerance [IGT] or diabetes) and had more features of the insulin resistance syndrome, despite showing similar body composition as controls. The plasma concentration of the sTNFR2 was higher and insulin sensitivity (%S) was lower in the relatives' group than in the controls. Likewise, the TNF-alpha -863A allele was more commonly detected in the control group (10 of 41) than in the relative's group (2 of 36, P =.029). In a multivariate linear regression analysis, neither TNF-alpha -863A allele nor sTNFR2 independently determined %S. Only body mass index (BMI) and the presence of a positive family history of DM were independent determinants of insulin resistance. In summary, our study showed a lower rate of TNF-alpha -863A allele and higher concentrations of sTNFR2 in first-degree relatives of DM subjects. These findings could be included among the genetic, metabolic, and clinical heterogeneity that characterizes the pathophysiology of DM. The presence of abnormalities in the TNF-alpha pathway could predispose to the development of DM in subjects at risk for the disease.

Adult↗
PubMed2003

[Ponderal evolution in the Girona population, 1989-1999].

BACKGROUND AND OBJECTIVE: Despite the number of plans leading to lose weight among individuals in the developed countries, the prevalence of obesity has increased since 1980. The knowledge of ponderal evolution in a given population is very important because the adverse effects of obesity vary greatly among individuals and populations. The objective of the present paper was to determine the modifications in the different degrees of body adiposity in a population in Catalunya. PATIENTS AND METHODS: A measurement was made of weight and height of 24554 users aged over 14 years (10595 males and 13959 females) attended at four basic health areas (BHA): Girona 1, Girona 4, Salt and Camprodon, and a Primary Health Center (PHC) in the Girona province, for a five-year period, 1995-1999. The prevalence of the different degrees of obesity was compared with that obtained in a previous study with 6373 individuals during the 1986-1989 period (4,579 males and 1794 females). RESULTS: The prevalence of women with overweight (defined as a body mass index [BMI] > 25 kg/m2) increased from 7.3% (1986-1989, study 0) to 17.6% (1995-1999, study 1) for women aged 15 to 24 years ( p < 0.001), from 17.9 % to 28.1% for women aged 25 to 34 years (p < 0.001), and from 37.5% to 44.7 % for women aged 35 to 44 years (p < 0.001). In the latter age group, the proportion of women with obesity (BMI > 30 kg/m2) increased from 6.9% to 12.9%. Similar trends were observed among men, and the change in the 35-44 year age group (from 10.5 % of obese men to 16% [p < 0.001]), and 55 to 65 years (from 16.6% of obese men to 22.7% [p < 0.001] was particularly significant. And lastly, it is also noteworthy the proportion of individuals with low weight (BMI < 18.5 kg/m2) which increased from 7.3% to 11.6% for women aged 15 to 24 years, and from 0.3% to 2.2% for women aged 35 to 44 years. This trend was also observed for men aged 15 to 24 years (11% to 17.2%). CONCLUSIONS: The relative increase in the prevalence of overweight and obesity runs in parallel to that found in other surrounding countries. Also, it is worth mentioning that among women aged 15 to 24 years the increase in the prevalence of low weight and obesity is almost identical, which invalidates the mean and median values as a means to assess the ponderal evolution in this population. The current compartmentalization between the extreme BMIs, particularly among the youngest portion of population should be addressed from a multidisciplinary perspective.

Adolescent↗
PubMed2002

Bone mineral mass is associated with interleukin 1 receptor autoantigen and TNF-alpha gene polymorphisms in post-menopausal Mediterranean women.

Bone mass is known to be under genetic control. Interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha are strong inductors of bone resorption. The estrogenic deficiency that occurs during menopause leads to an increase in the production of these cytokines. We analyzed the genetic susceptibility of several polymorphisms of the interleukin-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha genes in lumbar spine and hip bone mass in a sample of post-menopausal Caucasian Mediterranean women with osteoporosis. 104 post-menopausal osteoporotic women (58.6+/-4.8 yr) and 51 post-menopausal women without osteoporosis as the control group (57.2+/-4.5 yr) were studied. The osteoporotic group was in turn sub-classified into severe and non-severe osteoporosis. The variable number of tandem repeats IL1-ra, IL-6 SfaNI and TNF-alpha NcoI genetic polymorphisms were studied. Biochemical markers of bone turnover were measured in blood and urine. Women carrying the A2 allele (A2+) of the IL-1ra gene showed greater BMD in the lumbar spine (p=0.02) and hip (p=0.006), compared to those not carrying the allele (A2-). The IL-6 polymorphism studied in its 5' flanking region did not show any association with BMD values. The TNF-alpha gene G allele was associated with a greater bone mass in the non-severe osteoporotic subgroup, both in the lumbar spine (p=0.0007) and in the hip (p=0.02). Likewise, genotype combination A2+GG was associated to a greater hip BMD at the femoral neck and Ward triangle levels (p=0.02). We conclude that both IL-1ra and TNF-alpha can be candidate loci to be studied in the susceptibility to develop post-menopausal osteoporosis.

Alleles↗
PubMed2002

Short-term mortality of myocardial infarction patients with diabetes or hyperglycaemia during admission.

AIM: The hypothesis that patients with hyperglycaemia during admission, regardless of previous diagnosis of diabetes, have worse prognosis than those with normal glucose values is controversial. The objective was to assess the role of hyperglycaemia on short-term mortality after myocardial infarction (MI). METHODS AND RESULTS: A cohort study nested in a prospective registry of MI patients in the reference hospital of Gerona, Spain was performed. All consecutive MI patients under 75 were registered between 1993 and 1996. Patient and clinical characteristics, including previous diagnosis of diabetes, glycaemia on admission and in the next four days, were recorded. Patients with glycaemia on admission or four day mean glycaemia >6.67 mmol/l were considered hyperglycaemic. The main outcome measure was mortality at 28 days. Of 662 patients with MI included, 195 (29.7%) had previously known diabetes mellitus, but 457 (69.0%) had glycaemia >6.67 mmol/l on admission. Patients with hyperglycaemia on admission were older, more often female, more frequently had a previous diagnosis of diabetes, developed more complications, and had higher 28 day mortality. The effect of admission glycaemia >6.67 mmol/l on 28 day mortality was independent of major confounding factors, particularly previous diagnosis of diabetes (OR=4.20, 95% confidence intervals 1.18 to 14.96). CONCLUSIONS: Higher 28 day mortality was observed among MI patients with glycaemia on admission >6.67 mmol/l compared with patients with lower levels, independently of major confounding variables and, particularly, previous diagnosis of diabetes. This early, simple, and inexpensive marker of bad prognosis after MI should prompt the application of more aggressive treatment of MI and risk factors and, probably, of glycaemia during admission.

Adult↗
PubMed2002

Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus.

OBJECTIVE: To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin. METHODS: The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured. RESULTS: Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men. CONCLUSIONS: PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.

Aged↗
PubMed2001

[Body mass index (BMI) and percent fat mass. A BMI > 27.5 kg/m2 could be indicative of obesity in the Spanish population].

BACKGROUND: The World Health Organization (WHO) defines obesity as a condition of excessive fat accumulation to the extent that health and well-being are affected. For population studies, the measurement of weight, corrected for height, is still the method of choice (BMI). In Caucasian populations, the BMI cut-off point for obesity (30 kg/m2) corresponds with a percent body fat (PFM) of over 25% in young adult males and 35% in young adult females. However, the relation between BMI and PFM is not uniform among populations. It is important to define in each population the threshold of BMI which corresponds to the definition of obesity. PATIENTS AND METHOD: BMI was calculated in 282 subjects. PFM was analyzed using Bio-electrical impedance. Blood pressure, serum glucose and insulin, and the fasting insulin resistance index were also determined in all subjects to analyze the metabolic impact. RESULTS: The PFM of 25% in males and 35% in females corresponded to a BMI of 27.5 and 27.4 kg/m2, respectively. The slope of the relationship between the degree of obesity and comorbilities (insulinemia, fasting insulin resistance index and blood pressure) was strengthened above 26 kg/m2 in men and 24 kg/m2 in women. CONCLUSIONS: BMI that corresponds to a PFM previously defined as obesity is lower in our population in comparison with other Caucasian populations. Our results confirm that is impossible to compare the prevalence of obesity among populations using exclusively the BMI. It will be important to define, using reference methods, whether these findings have physiological impact or not, and if this cut-off of BMI determines an increment in cardiovascular and overall mortality using epidemiological approaches.

Adipose Tissue↗
PubMed2001

No decrease in free IGF-I with increasing insulin in obesity-related insulin resistance.

OBJECTIVE: Different facts suggest that the insulin growth factor (IGF)/ insulin growth factor-binding protein (IGFBP) system may be regulated by factors other than growth hormone. It has been proposed that, in healthy subjects, free IGF-I plays a role in glucose metabolism. The role of free IGF-I in glucose homeostasis in insulin resistance is poorly understood. This study was undertaken to evaluate the effects of acute changes in plasma glucose and insulin levels on free IGF-I and IGFBP-1 in obese and non-obese subjects. RESEARCH METHODS AND PROCEDURES: Nineteen lean and 24 obese subjects were investigated. A frequently sampled intravenous glucose tolerance test was performed. Free IGF-I and IGFBP-1 were determined at 0, 19, 22, 50, 100, and 180 minutes. RESULTS: Basal free IGF-I levels tended to be higher and IGFBP-1 lower in obese than in lean subjects. IGFBP-1 levels inversely correlated with basal insulin concentration. To determine the effects of insulin on the availability of free IGF-I and IGFBP-1, changes in their plasma concentrations were measured during a frequently sampled intravenous glucose tolerance test. After insulin administration, a significant suppression of free IGF-I at 22% was observed in lean subjects. In contrast, plasma-free IGF-I levels remained essentially unchanged in the obese group. The differences between both groups were statistically significant at 100 minutes (p < 0.01) and 180 minutes (p < 0.05). Serum IGFBP-1 was suppressed to a similar extent in both groups. DISCUSSION: These data suggest that the concentrations of free IGF-I and IGFBP-1 are differentially regulated by obesity. Obesity-related insulin resistance leads to unsuppressed free IGF-I levels.

Adult↗
PubMed2001

Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance.

We have previously described that serum corticosteroid binding globulin (CBG) concentrations are associated with insulin secretion. The present study was designed to evaluate the effects of changing insulin concentrations, both endogenous and after exogenous insulin administration, on circulating CBG levels in vivo. Serum CBG concentrations were measured during an insulin-modified frequently sampled intravenous (IV) glucose tolerance test (FSIVGT) in 14 lean and 19 obese otherwise healthy subjects with varying degrees of glucose tolerance. Acute insulin response to glucose (AIRg) correlated significantly with serum CBG concentrations at time 0 (r = -.38, P =.029), 22 minutes (r = -.41, P =.01), 50 minutes (r = -.41, P =.01), and 180 minutes (r = -.39, P =.02). Insulin sensitivity (S(I)) was not associated with serum CBG concentration at time 0 (r = -.16, P = not significant [NS]), but correlated significantly with CBG concentration at 22 minutes (r = -.41, P =.02) and 50 minutes (r = -.35, P =.048) of the FSIVGT. In lean subjects, serum CBG concentration decreased significantly after IV insulin from 37.9 +/- 5.4 to 35.4 +/- 3 mg/L (P =.02) and returned to basal levels thereafter. In contrast, obese, glucose-tolerant subjects had lower CBG levels than lean and obese glucose intolerant subjects (33.8 +/- 3.0 v 37.9 +/- 5.4 and 39.8 +/- 4.4 mg/L, respectively), and their serum CBG concentrations remained unchanged during FSIVGT. Mean serum-free insulin-like growth factor-I (IGF-I) concentrations steadily declined from 1.21 +/- 0.81 to 0.8 +/- 0.36 microg/L during the FSIVGT, and this effect was restricted to lean subjects. Basal serum-free IGF-I did not correlate with CBG levels at time 0, but correlated inversely with the serum CBG concentrations at 22 minutes (r = -.36, P =.04). Stepwise multivariant analysis showed that AIRg (P =.035) and S(I) (P =.046), but not free IGF-I levels, independently contributed to 28% of CBG variance at 22 minutes. These results suggest that insulin, but not IGF-I, constitutes an important negative regulator of CBG liver synthesis. Endogenous and exogenous insulin do not affect serum CBG concentrations in insulin-resistant obese subjects with preserved or decreased insulin secretion. Obese glucose-tolerant subjects are hypothesized to exhibit tonically inhibited serum CBG levels. In contrast, in lean subjects, the higher the insulin secretion the lower the serum CBG concentration. The mechanisms of this CBG inhibitory effect exerted by insulin and its implication on cortisol homeostasis and fat distribution in humans await further investigations.

Adult↗
PubMed2001

Circulating granulocyte-macrophage colony-stimulating factor and serum fatty acid composition in men and women.

Atherosclerosis is increasingly recognized as an inflammatory disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine, recently implicated as a prominent component of the regulatory network involved in atherogenesis. We aimed to study the relationship between circulating GM-CSF levels and serum fatty acid (FA) composition in 78 healthy subjects. The latter was analyzed by gas-liquid chromatography and GM-CSF by a high-sensitivity commercial enzyme-linked immunosorbent assay (ELISA). Among women (n = 40), serum GM-CSF levels were found to be positively associated with the proportion of palmitic acid (C16:0) and negatively with linoleic acid (C18:2omega-6), docosahexaenoic acid (DHA, C22:6omega-3), and the proportion of total essential FA. After excluding smoking women (n = 6), the associations among GM-CSF and serum linoleic acid concentration (r = -0.49, P =.003), arachidonic acid (r = -0.52, P =.001), and DHA (r = -0.34, P =.04) were strengthened. The ratio of palmitic to linoleic and DHA acids was the single best predictor of serum GM-CSF in all subjects. Together with arachidonic acid, it contributed to 22% of the GM-CSF variance in women, after taking into account the effects of age, body mass index (BMI), blood pressure, and smoking status. None of these associations were observed among men. In conclusion, serum FA composition is associated with circulating GM-CSF specifically in women. As human arterial and venous smooth muscle cells release GM-CSF, and treatment of endothelial cells with oxidized low-density lipoproteins results in a rapid expression of GM-CSF, the mechanisms involved in these associations and the sex-linked differences should be further explored.

Adult↗