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Biomedical subjects

Dorte Glintborg

Publications and source records attributed to Dorte Glintborg.

6 recordsLinked to original sources

Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome.

OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study. SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-(3)H glucose, and indirect calorimetry were performed before and after the intervention period. RESULT(S): Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E(2) and T levels did not change significantly. CONCLUSION(S): Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.

Adult↗

Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls.

OBJECTIVE: Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels. DESIGN: Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined. METHODS: Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase. RESULTS: Adiponectin levels were significantly decreased in obese PCOS patients compared with weight-matched controls (geometric mean (-2 to 2 s.d.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P<0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) microg/l, P<0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass. CONCLUSION: Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.

Absorptiometry, Photon↗

Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome.

BACKGROUND: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. OBJECTIVE: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. DESIGN: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood sampling for measurement of GH. RESULTS: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant changes were observed in Ferriman Gallwey score or androgen levels. CONCLUSION: Pioglitazone treatment significantly increased GHRH-stimulated GH levels and 24-h pulsatile GH secretion, probably directly or indirectly due to improved insulin sensitivity.

Absorptiometry, Photon↗

Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism.

OBJECTIVE: The mechanisms leading to higher bone mineral density (BMD) in hirsute patients than in healthy controls have seldom been examined. We compared the metabolic, hormonal and bone metabolic parameters in hirsute patients and female controls and correlated BMD and bone metabolic parameters with testosterone, oestradiol and metabolic parameters. PATIENTS: Fifty-one Caucasian, reproductive-aged, hirsute patients referred to the outpatient clinic of an academic tertiary-care medical centre and 63 healthy, female Caucasian controls matched for season, weight and age. MEASUREMENTS: BMD (hip, neck, lumbar and total BMD), bone metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium, phosphate and 25-hydroxyvitamin D (25OHD)) and endocrine profiles (androgen status, oestradiol and insulin) were evaluated during follicular phase. Oestradiol measurement was repeated during cycle days 8-12. RESULTS: Lumbar and neck BMD levels were significantly higher in hirsute patients than in controls: (mean +/- SD): lumbar BMD 1.10 +/- 0.12 vs. 1.06 +/- 0.10 g/cm2 and neck BMD 0.91 +/- 0.11 vs. 0.87 +/- 0.12 g/cm2, P < 0.05. Fasting insulin and free testosterone levels were significantly higher in hirsute patients than in controls. Free testosterone correlated positively with neck and hip BMD levels in hirsute patients. During multiple regression analysis, testosterone, oestradiol and waist/hip ratio (WHR) were found to have positive effects on BMD levels independent of body mass index (BMI). 25OHD levels were significantly lower in hirsute patients [42 (13-131)] than in controls [72 (27-196)] nmol/l (geometric mean +/- 2SD), P < 0.001]. CONCLUSION: Hirsute patients demonstrated significantly higher bone mineral density levels than controls, which could be explained by hyperinsulinaemia and higher testosterone levels in hirsute patients compared with controls. The pathogenesis for significantly lower 25-hydroxyvitamin D levels in hirsute patients compared with controls needs to be evaluated in future studies.

Adult↗

Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis.

OBJECTIVE: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. DESIGN: Systematic, retrospective audit. SETTING: Academic tertiary-care medical center. PATIENT(S): Three hundred forty women with hirsutism as the referral diagnosis. INTERVENTION(S): Hormone analyses and ACTH tests during cycle days 2-8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. MAIN OUTCOME MEASURE(S): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose-stimulated levels of insulin and capillary blood glucose. RESULT(S): Two hundred one patients were diagnosed as having idiopathic hirsutism (IH) and 134 as having polycystic ovary syndrome (PCOS). End diagnosis: prolactinoma: n = 1, Cushing's syndrome: n = 1, androgen-producing ovarian tumor: n = 1, late-onset 21-hydroxylase defects: n = 2. During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. CONCLUSION(S): Initial evaluation of hirsute patients with irregular menses should include serum (s)-17alpha-hydroxyprogesterone, s-prolactin, s-Testosterone (T), and s-sex hormone-binding globulin. Further evaluation is needed in patients with markedly elevated s-T or with clinical Cushing's syndrome. Hirsute patients have a high risk of diabetes, although this could be due to the high number of overweight patients among this population.

Adrenal Hyperplasia, Congenital↗

[Osteoarthritis].

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Anti-Inflammatory Agents, Non-Steroidal↗