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José I Botella-Carretero

Publications and source records attributed to José I Botella-Carretero.

15 recordsLinked to original sources
PubMed2006

Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome.

CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome. OBJECTIVE: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery. DESIGN: This was a case-control study. SETTINGS: We conducted the study in an academic hospital. PATIENTS: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity. INTERVENTIONS: Biopsy samples of omental fat were obtained during bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was high-density oligonucleotide arrays. RESULTS: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome. CONCLUSION: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.

Adipose Tissue↗
PubMed2006

Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women.

BACKGROUND: Surprisingly, the prevalence of polycystic ovary syndrome (PCOS) in otherwise unselected overweight or obese women is unknown, despite obesity being frequent in patients with PCOS. We conducted the present study to obtain an unbiased estimate of the prevalence of PCOS in unselected overweight and obese premenopausal women from Spain. METHODS: All premenopausal women reporting to the Department of Endocrinology, Hospital Universitario Ramón y Cajal, for dietary treatment of overweight or obesity from May 2002 to December 2005 were prospectively recruited. Women referred for any other reason were automatically excluded to avoid selection bias. Diagnosis of PCOS relied on the presence of clinical and/or biochemical hyperandrogenism, oligo-ovulation, and exclusion of secondary causes. Anthropometric measurements, hirsutism scores, and androgen, gonadotropin, metabolic, and lipid profiles were obtained. RESULTS: Of a total of 113 consecutive women recruited, 32 (28.3%) were diagnosed as having PCOS (95% confidence interval, 20.0%-36.6%). The prevalence of PCOS was not different when considering the degree of obesity. Another 3 women presented with hyperandrogenemia without oligo-ovulation, 2 had idiopathic hirsutism, 2 had chronic oligomenorrhea without clinical or biochemical hyperandrogenism, and 2 had oligomenorrhea with hyperprolactinemia, precluding the diagnosis of PCOS. The remaining 72 women (63.7%) had no evidence of hyperandrogenism or reproductive abnormalities. CONCLUSIONS: Our results demonstrate a 28.3% prevalence of PCOS in overweight and obese women from Spain, which is markedly increased compared with the 5.5% prevalence of PCOS in lean women of our country. Therefore, PCOS must be routinely ruled out in overweight and obese premenopausal women seeking advice for weight loss.

Adult↗
PubMed2006

The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women.

BACKGROUND: Because serum paraoxonase activity is influenced by the -108C/T polymorphism in the PON1 gene, we studied its involvement in the decreased paraoxonase activity recently described in the polycystic ovary syndrome (PCOS). METHODS: Paraoxonase activity, PON1-108C/T genotypes and clinical, hormonal and biochemical variables were evaluated in a case-control study involving 139 consecutive PCOS patients and 85 healthy controls matched for BMI and prevalence of smoking. RESULTS: Women homozygous for -108T presented with reduced serum paraoxonase activity compared with carriers of C alleles (P < 0.001), both in PCOS patients and in controls. Although homozygosity for T alleles was more prevalent in PCOS patients than in controls (P = 0.003), serum paraoxonase activity was not significantly different in the PCOS and control groups. In a stepwise multivariate linear regression model, homozygosity for PON1-108T alleles was the only significant predictor of the logarithm of serum paraoxonase activity (beta = -0.328, t = -4.176, P < 0.001). CONCLUSIONS: In premenopausal women from the Spanish population, the PON1-108C/T polymorphism, and not PCOS, is an important determinant of serum paraoxonase activity.

Aryldialkylphosphatase↗
PubMed2006

Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal.

OBJECTIVE: Previous studies addressing the influence of thyroid hormones on serum levels of adipokines yielded conflicting results. We aimed to study the impact of short-term overt hypothyroidism on serum leptin, resistin, and adiponectin levels in an in vivo human model. DESIGN: Twenty-two women with differentiated thyroid carcinoma were studied the last day of their thyroxine-suppressive treatment, 4-7 days after withdrawal, and the day before whole-body scanning. Evaluations included serum thyroid hormone, leptin, resistin, and adiponectin concentrations, fasting glucose and insulin, lipid profiles, body temperature, body mass index, and total body fat mass. MAIN OUTCOMES: Thyroid function changed from subclinical or mild hyperthyroidism to normal free thyroxine and triiodothyronine levels, ending in overt hypothyroidism. Thyroxine withdrawal resulted in an increase in serum resistin (p = 0.007) and leptin (p = 0.006) concentrations, whereas adiponectin levels remain unchanged. A significant decrease in body temperature during thyroxine withdrawal was paralleled by a decrease in fasting glucose (p = 0.006) and insulin resistance (p = 0.033), which occurred despite an increase in estimated total body fat mass. CONCLUSION: Thyroid hormones are important regulators of energy balance and intermediate metabolism, influencing the serum concentrations of leptin and resistin.

Adiponectin↗
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↗
PubMed2005

The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery.

CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with obesity. However, there are very few data about PCOS in morbid obesity, especially with regard to its evolution after bariatric surgery. OBJECTIVE: The objective of this study was to evaluate the response of PCOS to the sustained and marked weight loss achieved by bariatric surgery in morbidly obese women. DESIGN: This was a longitudinal prospective nonrandomized evaluation. SETTINGS: The study was performed at an academic hospital. PATIENTS: Thirty-six consecutive premenopausal women submitted to bariatric surgery were screened for PCOS, which was present in 17. INTERVENTIONS: Bariatric surgery was performed. MAIN OUTCOME MEASURES: Hyperandrogenism, menstrual function, and insulin resistance were estimated before and at least 6 months after bariatric surgery in 12 patients with PCOS. RESULTS: Weight loss (41 +/- 9 kg after 12 +/- 5 months) was paralleled by decreases in the hirsutism score (from 9.5 +/- 6.8 to 4.9 +/- 4.2; P = 0.001), total (69 +/- 32 to 42 +/- 19 ng/dl; P < 0.02) and free testosterone (from 1.6 +/- 0.7 to 0.6 +/- 0.3 ng/dl; P < 0.005), androstenedione (from 4.1 +/- 1.5 to 3.0 +/- 0.9 ng/ml; P < 0.02), and dehydroepiandrosterone sulfate (from 2000 +/- 1125 to 1353 +/- 759 ng/ml; P < 0.005); amelioration of insulin resistance estimated by homeostasis model assessment (from 6.0 +/- 3.0 to 1.6 +/- 1.0; P < 0.001); and restoration of regular menstrual cycles and/or ovulation in all patients. CONCLUSIONS: The PCOS is a frequent finding in women with morbid obesity and may resolve after weight loss induced by bariatric surgery.

Adult↗
PubMed2005

Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls.

BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.

Adult↗
PubMed2005

REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine.

CONTEXT: Combined infusion of levothyroxine plus liothyronine, as opposed to levothyroxine alone, is the only way of restoring the concentrations of circulating TSH, T4, and T3 as well as those of both T4 and T3 in all tissues of thyroidectomized rats. Considering the substantial differences in thyroid hormone secretion, transport, and metabolism between rats and humans, whether or not combined levothyroxine plus liothyronine replacement therapy has advantages over treatment with levothyroxine alone in hypothyroid patients is still questioned. EVIDENCE ACQUISITION: We conducted a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Nine controlled clinical trials were identified that compared treatment with levothyroxine alone and treatment with combinations of levothyroxine plus liothyronine and included a sufficient number of adult hypothyroid patients to yield meaningful results. In only one study did the combined therapy appear to have beneficial effects on the mood, quality of life, and psychometric performance of the patients over levothyroxine alone. These results have not been confirmed by later studies using either T3 substitution protocols or approaches with fixed combinations of levothyroxine plus liothyronine, including those based on the physiological proportion in which T3 and T4 are secreted by the human thyroid. However, in some of these studies the patients preferred levothyroxine plus liothyronine combinations, for reasons not explained by changes in the psychological and psychometric tests employed. Yet patients' preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine, even in the small doses used in these studies. CONCLUSIONS: Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism.

Drug Therapy, Combination↗
PubMed2005

A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome.

CONTEXT: The R453Q variant in the hexose-6-phosphate dehydrogenase gene (H6PD) and 83557insA mutations in 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 gene (HSD11B1) interact, resulting in cortisone reductase deficiency (CRD), a rare disorder characterized by a polycystic ovary syndrome (PCOS)-like phenotype. OBJECTIVE: The objective was to study these mutations in PCOS. DESIGN: The design was a case-control study. SETTING: The study was conducted in an academic hospital. PARTICIPANTS: A total of 116 PCOS patients and 76 nonhyperandrogenic controls participated. MAIN OUTCOME MEASURES: Genotype distributions and influence of genotypes on clinical and biochemical variables and, in 28 patients and 12 controls, estimates of 11betaHSD oxoreductase activity were the main outcome measures. RESULTS: Four controls and five patients presented three of four mutant alleles in H6PD R453Q and HSD11B1 83557insA, which is the genotype observed in some subjects with CRD. Estimates of 11betaHSD oxoreductase activity were measured in six of these nine women, ruling out CRD. Moreover, H6PD R453Q and HSD11B1 83557insA genotypes, either separately or in combination, did not influence 11betaHSD oxoreductase activity. The distribution of H6PD R453Q genotypes (R/R, R/Q, and Q/Q) was different in patients and controls (42% of controls and 63% of PCOS patients were R/R; 53% of controls and 31% of PCOS patients were R/Q; and 5% of controls and 6% of PCOS patients were Q/Q; chi(2) = 9.1; P = 0.011). Patients homozygous for R453 alleles presented with increased cortisol and 17-hydroxyprogesterone levels, compared with carriers of Q453 alleles, but these differences were not observed in controls. On the contrary, HSD11B1 83557insA genotypes were not associated with PCOS and did not influence any phenotypic variable. CONCLUSIONS: Digenic triallelic genotypes of the H6PD R453Q variant and HSD11B1 83557insA mutation do not always cause CRD. On the contrary, the H6PD R453Q variant is associated with PCOS and might influence its phenotype by influencing adrenal activity.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2005

Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone.

BACKGROUND: Substituting part of the dose of l-thyroxine with small but supraphysiologic doses of liothyronine in hypothyroid patients has yielded conflicting results. OBJECTIVE: To evaluate combinations of L-thyroxine plus liothyronine in hypothyroid patients that match the proportions present in normal secretions of the human thyroid gland. DESIGN: Randomized, double-blind, crossover trial. SETTING: Academic research hospital. PARTICIPANTS: 28 women with overt primary hypothyroidism. INTERVENTION: Crossover trial comparing treatment with l-thyroxine, 100 microg/d (standard treatment), versus treatment with L-thyroxine, 75 microg/d, plus liothyronine, 5 microg/d (combination treatment), for 8-week periods. All patients also received L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d (add-on combination treatment), for a final 8-week add-on period. MEASUREMENTS: Primary outcomes included serum thyroid hormone levels, results of quality-of-life and psychometric tests, and patients' preference. Multiple biological thyroid hormone end points were studied as secondary outcomes. RESULTS: Compared with standard treatment, combination treatment led to lower free thyroxine levels (decrease, 3.9 pmol/L [95% CI, 2.5 to 5.3 pmol/L]), slightly higher serum levels of thyroid-stimulating hormone (increase, 0.62 mU/L [CI, 0.01 to 1.23 mU/L]), and unchanged free triiodothyronine levels. No improvement was observed in the other primary and secondary end points after combination treatment, with the exception of the Digit Span Test, in which the mean backward score and the mean total score increased slightly (0.6 digit [CI, 0.1 to 1.0 digit] and 0.8 digit [CI, 0.2 to 1.4 digits], respectively). The add-on combination treatment resulted in overreplacement. Levels of thyroid-stimulating hormone decreased by 0.85 mU/L (CI, 0.27 to 1.43 mU/L) and serum free triiodothyronine levels increased by 0.8 pmol/L (CI, 0.1 to 1.5 pmol/L) compared with standard treatment; 10 patients had levels of thyroid-stimulating hormone that were below the normal range. Twelve patients preferred combination treatment, 6 patients preferred the add-on combination treatment, 2 patients preferred standard treatment, and 6 patients had no preference (P = 0.015). LIMITATIONS: Treatment with L-thyroxine, 87.5 microg/d, plus liothyronine, 7.5 microg/d, was an add-on regimen and was not randomized. CONCLUSIONS: Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine alone, yet patients prefer combination treatment.

Adolescent↗
PubMed2005

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal.

OBJECTIVE: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model. SUBJECTS AND DESIGN: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4-7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry. RESULTS: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean+/-s.d., 280+/-122 vs 183+/-106 pg/ml, F = 3.192, P = 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368+/-1480 vs 2564+/-846 pg/ml, F = 21.324, P < 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9+/-8.6 vs 10.5+/-3.6%, F = 4.977, P = 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively. CONCLUSION: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans.

Adult↗
PubMed2004

Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity.

Low-grade chronic inflammation is involved in the pathogenesis of the metabolic syndrome and atherosclerosis, and serum levels of inflammatory cytokines are useful cardiovascular risk markers. We have studied serum IL-18 concentrations in women with polycystic ovary syndrome (PCOS), focusing on its relationship with obesity and indexes of insulin resistance. Sixty consecutive women with PCOS and 34 healthy women were recruited. Serum levels of IL-18 and lipid and hormone profiles were measured. The insulin sensitivity index was calculated from glucose and insulin concentrations during an oral glucose tolerance test. Data were submitted to a multivariate general linear model introducing age as a covariate. Serum IL-18 levels were increased in PCOS patients compared with controls (P = 0.031) and in obese women compared with lean women (P = 0.018). No interaction between PCOS and obesity was found, suggesting that the influence of PCOS on serum IL-18 concentrations studied here was not different in lean women compared with obese women and that the influence of obesity on serum IL-18 concentrations was the same in the PCOS and control groups. Serum IL-18 levels correlated, after logarithmic transformation, with body mass index (r = 0.38; P < 0.0002), waist-to-hip ratio (r = 0.33; P < 0.001), and total testosterone levels (r = 0.24; P < 0.02), and inversely with the insulin sensitivity index (r = -0.23; P < 0.03). In conclusion, PCOS and obesity induce an increase in serum IL-18 levels, which are also associated with several indexes of global and visceral adiposity and with insulin resistance.

Adult↗
PubMed2004

Chronic thyrotropin-suppressive therapy with levothyroxine and short-term overt hypothyroidism after thyroxine withdrawal are associated with undesirable cardiovascular effects in patients with differentiated thyroid carcinoma.

To evaluate cardiovascular functionality in patients with thyroid cancer, we have performed echocardiography and ambulatory blood pressure monitoring in 19 women with differentiated thyroid carcinoma during thyroxine withdrawal, at three time points: the last day on TSH-suppressive thyroxine doses (subclinical or mild hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free triiodothyronine (FT3) levels), and before 131I whole body scanning (overt hypothyroidism). Twenty-one healthy euthyroid women served as controls. When compared with the values at visit 2, when patients had normal serum FT4 and FT3 levels, night-time systolic and mean blood pressure were increased when the patients were mildly hyperthyroid, and night-time systolic, diastolic and mean blood pressure were increased during overt hypothyroidism. The proportion of nondippers (absence of nocturnal decline in blood pressure) was markedly increased compared with healthy controls (7%), when patients were hyper- or hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and FT3 levels (12%). No changes were observed in office blood pressure or in daytime ambulatory blood pressure readings. Diastolic function worsened during thyroxine withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A ratio and the isovolumic relaxation time increased), and cardiac output decreased in parallel with the decrease in heart rate and systolic blood flow. In conclusion, the chronic administration of TSH-suppressive doses of thyroxine and the withdrawal of thyroxine frequently used for the management of differentiated thyroid carcinoma, are associated with undesirable cardiovascular effects.

Adult↗