Gemma Villuendas

Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

Aims/HypothesisIncreased serum inflammatory markers have been found in obesity and insulin-resistant states, and could play a causative role in insulin resistance, atherosclerosis and cardiovascular disease. The polycystic ovary syndrome represents a human model of insulin resistance because both lean and obese polycystic ovary syndrome patients are insulin-resistant compared with non-hyperandrogenic women. We evaluated whether obesity, insulin resistance, or both, are related to the increased concentrations of inflammatory markers in pre-menopausal women.MethodsWe compared 35 patients with polycystic ovary syndrome and 28 healthy women, paired for BMI, prevalence of obesity and smoking. Measurements included serum inflammatory markers, BMI, waist-to-hip ratio, blood pressure, serum glucose, insulin, lipid and hormone concentrations, and insulin sensitivity index.ResultsThe insulin sensitivity index was reduced in polycystic ovary syndrome patients compared with controls. However, no differences were observed between both groups in C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. When considering patients and controls as a whole, C-reactive protein and interleukin 6, were increased in obese subjects compared with lean women. Inverse correlations existed between insulin sensitivity index and C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. Only the weak correlation with C-reactive protein persisted after controlling for BMI.Conclusion/interpretationObesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women.

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.

Common single nucleotide polymorphisms in intron 3 of the calpain-10 gene influence hirsutism

OBJECTIVE To study three common polymorphisms in intron 3 of the calpain-10 gene (CAPN10) in hyperandrogenic patients. DESIGN Case-control study. SETTING Academic hospital. PATIENT(S) Ninety-seven hyperandrogenic patients and 37 healthy controls. INTERVENTION(S) Basal and adrenocorticotropin-stimulated serum samples and genomic DNA samples were obtained during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S) Genotyping of the UCSNP43, UCSNP44, and UCSNP45 polymorphisms in CAPN10 and serum androgen levels. RESULT(S) Sixteen patients had idiopathic hirsutism, defined as normal serum androgen levels and regular menstrual cycles. Eighty-one hyperandrogenic patients (those presenting with hyperandrogenemic hirsutism or the polycystic ovary syndrome) were analyzed further. UCSNP45 alleles were distributed differently among the study groups. Heterozygosity for the uncommon C allele was increased in patients with idiopathic hirsutism (31.3%) and reduced in hyperandrogenic patients (7.4%) compared with controls (16.2%). The UCSNP44 and UCSNP43 alleles were in linkage disequilibrium, and were distributed equally among patients with idiopathic hirsutism, hyperandrogenism, and controls. However, the uncommon A allele at UCSNP43 was associated with higher hirsutism score (mean [+/- SD], 9.9 +/- 6.8, 12.7 +/- 7.7, and 14.6 +/- 8.2 in GG, GA, and AA participants, respectively). No other differences were observed in clinical and biochemical characteristics, including insulin sensitivity, by CAPN10 variant. CONCLUSION(S) The C allele at the UCSNP45 locus in CAPN10 is associated with idiopathic hirsutism, and UCSNP43 influences the hirsutism score.

Role of the follistatin gene in women with polycystic ovary syndrome

OBJECTIVE To search for mutations in the coding exons of the follistatin gene of women diagnosed with polycystic ovary syndrome (PCOS). DESIGN Controlled clinical study. SETTING Tertiary institutional hospital. PATIENT(S) Thirty-four women diagnosed with PCOS and 15 healthy control women. INTERVENTION(S) Whole blood and serum samples were collected during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S) Circulating total testosterone (T), sex hormone-binding globulin (SHBG), calculated free T (FT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEAS), LH, FSH, E2, and basal and adenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP) were determined. Insulin resistance was estimated from fasting glucose and insulin levels, using the homeostasis model assessment. The coding regions of the follistatin gene were studied by heteroduplex analysis after polymerase chain reaction amplification. RESULT(S) Women with PCOS presented with higher body-mass index, insulin resistance, T, FT, A, and ACTH-stimulated 17-OHP serum concentrations and lower SHBG serum levels, as compared with controls. No differences were observed among the groups in serum DHEAS, basal 17-OHP, E(2), LH, and FSH. No mutations were found in coding regions of the follistatin gene, with the exception of a G to A change at cDNA position 951, resulting in a silent mutation. This change was present in 2 (5.9%) of 34 patients and 1 (6.7%) of 15 controls. CONCLUSION(S) Mutations in the coding regions of the follistatin gene do not appear to be related to PCOS.