| 1. |
- Comasco, Erika, et al.
(författare)
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Adipocytokines levels at delivery, functional variation of TFAP2 beta, and maternal and neonatal anthropometric parameters
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:10, s. 2130-2137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEAdipocytokines participate in the regulation of glucose metabolism and foetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokines levels and maternal and neonatal anthropometric characteristics.DESIGN AND METHODSA population-based sample of women was followed from delivery to six months postpartum. Adiponectin, leptin and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.RESULTSMaternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels and newborn females' weight.CONCLUSIONSThe present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuro-endocrine foetal programming.
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| 2. |
- Hudecova, Miriam, et al.
(författare)
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Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome : a long-term follow-up study
- 2011
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 95:3, s. 1146-1148
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.
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| 3. |
- Hudecova, Miriam, et al.
(författare)
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Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome-a long term follow-up
- 2011
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26:6, s. 1462-1468
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Tidskriftsartikel (refereegranskat)abstract
- Background: The overall risk of developing diabetes mellitus and glucose intolerance seems to be higher in women with polycystic ovary syndrome (PCOS) than in healthy women. The aim of this long-term follow-up study was to examine glucose tolerance and insulin sensitivity in middle-aged women previously diagnosed with PCOS in comparison with age-matched healthy controls. Methods: Women diagnosed with PCOS between 1987 and 1995 were invited to participate in the study. A total of 84 PCOS patients and 87 control subjects participated. Anthropometric (BMI, waist/hip ratio) and metabolic parameters (oral glucose tolerance test) were measured. Insulin sensitivity was expressed by the Matsuda index and beta cell function by the insulinogenic index. PCOS women were sub-grouped according to phenotype at the index assessment (with or without hyperandrogenism) and persistence of PCOS symptoms at the follow-up (persisting or resolved PCOS). Results: Eighteen (21.4%) PCOS patients and four (4.5%) controls had developed type 1 or type 2 diabetes or impaired glucose tolerance (IGT) at the follow-up investigation (P < 0.05). Matsuda insulin sensitivity index was lower and the insulinogenic index was increased in women with previously diagnosed PCOS compared with control subjects. In addition, PCOS patients with or without hyperandrogenism, and PCOS patients with persisting and resolved PCOS all had lower Matsuda insulin sensitivity index and increased insulinogenic index in comparison with controls. Conclusions: IGT and type 2 diabetes occurred more often in PCOS patients. Independent on PCOS phenotype at index assessment and persistence of PCOS symptoms at the follow-up investigation, women with PCOS had lower insulin sensitivity but a well-preserved beta cell function in comparison with control subjects.
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| 4. |
- Hudecova, Miriam, 1971-, et al.
(författare)
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Endothelial function in patients with polycystic ovary syndrome : a long-term follow-up study
- 2010
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 94:7, s. 2654-2658
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate pulse wave reflection and endothelial-dependent vasodilatation (EDV) in PCOS patients and age-matched healthy controls. Design: Long-term follow-up study. Setting: Department of Women’s and Children’s Health, Uppsala University, Sweden. Patient(s): Sixty-seven PCOS patients with a mean age of 43.3 years at the follow-up investigation and 66 age-matched controls. Intervention: Aplanation tonometry before and after b-2 receptor agonist (terbutaline) challenge. Main outcome measure(s): Baseline augmentation index (AI) aorta, baseline AI-radial, and change in AI-radial following terbutaline administration as a measure of EDV. Result(s): There was no difference in baseline AI-aorta between PCOS patients and control subjects. Change in AI-radial following terbutaline administration was less pronounced in PCOS patients in comparison to control subjects. This difference remained when adjusted for use of combined oral contraceptives/hormone replacement therapy and postmenopausal status but not after adjustment for BMI. Conclusion(s): Middle-aged PCOS patients display signs of endothelial dysfunction in comparison to age-matched controls, but this is largely due to the increased prevalence of independent risk factors for cardiovascular disease found in this group.
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| 5. |
- Hudecova, Miriam, et al.
(författare)
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Long-term follow-up of patients with polycystic ovary syndrome : reproductive outcome and ovarian reserve
- 2009
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 24:5, s. 1176-1183
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of the present study was to examine long-term reproductive outcome and ovarian reserve in an unselected population of women with polycystic ovary syndrome (PCOS). METHODS A total of 91 patients with confirmed PCOS and 87 healthy controls were included in the study. Patients had been diagnosed between 1987 and 1995 and at the time of the follow-up, subjects were 35 years of age or older. RESULTS: Among women who had attempted a pregnancy, 86.7% of PCOS patients and 91.6% of controls had given birth to at least one child. Among PCOS patients who had given birth, 73.6% had done so following a spontaneous conception. Mean ovarian volume and the number of antral follicles in PCOS patients were significantly greater than in control women (P < 0.001, respectively). PCOS patients also had higher serum concentrations of anti-Müllerian hormone and lower follicle-stimulating hormone levels. CONCLUSIONS: Most women with PCOS had given birth, and the rate of spontaneous pregnancies was relatively high. Together with the ultrasound findings and the hormonal analyses, this finding could imply that PCOS patients have a good fecundity, and an ovarian reserve possibly superior to women with normal ovaries.
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| 6. |
- Hudecova, Miriam, 1971-, et al.
(författare)
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Prevalence of diabetes, impaired glucose tolerance and insulin sensitivity in patients with polycystic ovary syndrome - a long term follow-up
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The aim of this long-term follow-up study was to examine glucose tolerance and insulin sensitivity in middle-aged women previously diagnosed with PCOS in comparison with age-matched healthy controls. Methods: Women diagnosed with PCOS between 1987 and 1995 were invited for the study. 84 PCOS patients and 87 control subjects, randomly selected from the general population, participated in the study. Anthropometric and metabolic parameters, including an oral glucose tolerance test, were examined. Results: Eighteen (21.4 %) PCOS patients had type 1 or type 2 diabetes or impaired glucose tolerance at the follow-up investigation, which was significantly more common than in control subjects (4.5 %), p < 0.05. Following the adjustment for BMI, insulin sensitivity measured by the Matsuda insulin sensitivity index was significantly lower in women with PCOS and the insulinogenic index, as a measure of beta-cell function, was elevated in PCOS patients in comparison to control subjects. Furthermore, both women with persisting and resolved PCOS at the follow-up investigation displayed decreased Matsuda insulin sensitivity index and increased insulinogenic index in comparison with control subjects. Women without clinical signs of hyperandrogenism at the index assessment displayed higher fasting insulin and proinsulin plasma concentrations than controls at the follow-up investigation. In addition, they had lower Matsuda insulin sensitivity index and higher insulinogenic index than controls. When adjusted for BMI, there was also a trend towards significantly lower Matsuda insulin sensitivity index and increased insulinogenic index at the follow-up investigation among women who had presented with hyperandrogenism at the index assessment. Conclusion: IGT and type 2 diabetes occurred more often in PCOS patients. Independent of PCOS phenotype at index assessment and persistence of PCOS symptoms at the follow-up investigation, women with PCOS had lower insulin sensitivity and increased beta-cell function in comparison with control subjects.
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| 7. |
- Hudecova, Miriam, 1971-
(författare)
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Reproductive and Metabolic Consequences of the Polycystic Ovarian Syndrome
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polycystic ovary syndrome (PCOS) is a complex clinical condition characterized by hyperandrogenism and chronic oligo/anovulation. Infrequent ovulation and metabolic alterations in women with PCOS are associated with subfertility and probably increased miscarriage rates compared with normal fertile women. The overall risk of developing type 2 diabetes and impaired glucose tolerance (IGT) is three- to sevenfold higher in PCOS women, and the onset of glucose intolerance seems to occur at an earlier age than in healthy controls. Women with PCOS also have several risk factors for cardiovascular disease, although it is unclear whether they actually experience more cardiovascular events than other women. Very few studies assessing the long-term reproductive and metabolic consequences in older women with previously confirmed PCOS have been conducted. In this long-term follow-up of women with PCOS, 84 women with a diagnosis of PCOS between 1987 and 1995 and age at the follow-up > 35 years and an age-matched population-based group of control women participated. Data on reproductive outcome, ovarian reserve, endothelial function, insulin sensitivity and beta-cell function were collected. According to our results most women with PCOS had given birth and the rate of spontaneous pregnancies was relatively high. The rate of miscarriages was not increased in PCOS patients and the ultrasound findings together with increased levels of anti-müllerian hormone suggested that their ovarian reserve is superior to women of similar age. PCOS women displayed signs of endothelial dysfunction, but this was largely due to the increased prevalence of independent risk factors for cardiovascular disease such as increased BMI, triglycerides and blood pressures. IGT and type 2 diabetes occurred more often in PCOS women. Free androgen levels and beta-cell function decreased over time whereas insulin sensitivity remained unchanged. Obesity at young age and progressive weight-gain rendered them more prone to be insulin resistant at the follow-up. Beta-cell function was increased in PCOS women in comparison with control subjects but declined over time. Independent of PCOS phenotype at the index assessment and persistence of PCOS symptoms at the follow-up investigation, premenopausal women with PCOS had lower insulin sensitivity and increased beta cell function in comparison with control subjects. Conclusion: The long-term reproductive outcomes of PCOS are similar compared to women with normal ovaries. Although symptoms and androgen levels are normalized over time, women with PCOS continue to display reduced insulin sensitivity and increased beta-cell function and they also have an increased risk of IGT and type 2 diabetes.
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| 8. |
- Lindahl, Magnus S., et al.
(författare)
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Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea
- 2007
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 87:1, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. DESIGN: Cross-sectional study. SETTING: Umeå University Hospital, Umeå, Sweden. PATIENTS: Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. RESULTS: Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. CONCLUSION: The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.
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| 9. |
- Pétursdóttir Maack, Heiðrún, et al.
(författare)
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Pregnancy in metabolic healthy and unhealthy obese women
- 2020
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:12, s. 1640-1648
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Obesity-associated adverse obstetric outcomes are well-known but still relatively rare and difficult to predict. Not all obese individuals are unhealthy, some have metabolically healthy obesity (MHO) and others have metabolic unhealthy obesity (MUO). Our aim was to investigate if the MHO and MUO classification could be used for prediction of obesity-associated complications in pregnancy.MATERIAL AND METHODS: We included 547 pregnant women with obesity, 2302 pregnant women with overweight, and 5852 normal weight pregnant women. The women with obesity were classified as MUO (n = 181, 33.1%) and MHO (n = 366, 66.9%) based on first trimester blood pressure, lipoprotein levels and non-fasting glucose levels. The risk of obstetric outcomes was evaluated by multivariable logistic regression. We compared cardiovascular risk markers in blood between obese pregnant women with MUO and MHO.RESULTS: Overall, 45.9% of women with MUO developed at least one adverse obesity-associated obstetric outcome, whereas corresponding proportions in women with MHO, overweight and normal weight were 35.0%, 27.6% and 21.2%, respectively. Following adjustment, the overall risk of at least one obesity-associated obstetric or perinatal complication in women with MUO, versus women with MHO, was increased, AOR 1.49 (95% CI 1.03 - 2.15), but the predictive value of the model was low. Women with MUO had altered levels of cardiovascular risk markers such as cathepsin S, adiponectin, and cystatin C in comparison to women with MHO.CONCLUSIONS: Women with MUO had an overall increased risk of adverse obstetric outcomes in comparison to women with MHO, but the classification had little relevance for risk prediction beyond that of body mass index.
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| 10. |
- Skalkidou, Alkistis, et al.
(författare)
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Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery : a nested case-control study within the UPPSAT cohort
- 2009
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:9, s. 1329-1337
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Tidskriftsartikel (refereegranskat)abstract
- Although postpartum depression (PPD) is a common condition, it often goes undiagnosed and untreated, with devastating consequences for the woman's ability to perform daily activities, to bond with her infant and to relate to the infant's father. Leptin, a protein synthesised in the adipose tissue and involved in regulation of food intake and energy expenditure has been related to depressive disorders, but studies report conflicting results. The aim of this study was to evaluate the association between serum leptin levels at the time of delivery and the subsequent development of postpartum depression in women, using data from a population-based cohort of delivering women in Uppsala, Sweden. Three hundred and forty seven women from which serum was obtained at the time of delivery filled out at least one of three structured questionnaires containing the Edinburgh Scale for Postnatal Depression (EPDS) at five days, six weeks and six months after delivery. Mean leptin levels at delivery did not significantly differ between the 67 cases of PPD and the 280 controls. Using linear regression analysis and adjusting for maternal age, body-mass index, smoking, interleukin-6 levels, duration of gestation and gender of the newborn, the EPDS scores at six weeks and six months after delivery were found to be negatively associated with leptin levels at delivery (p<0.05). Serum leptin levels at delivery were found to be negatively associated with self-reported depression during the first six months after delivery. No such association was found concerning serum IL-6 levels at delivery. If these finding are replicated by other studies, leptin levels at delivery could eventually serve as a biological marker for the prediction of postpartum depression.
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