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- Adams, Rachel, et al.
(författare)
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RHAPSODY, Biomarkers and Novel Clinical Trial design in type 2 diabetes (T2D) and prediabetes
- 2021
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Ingår i: Endocrinology, Diabetes and Metabolism. - : Wiley. - 2398-9238. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Developing a novel therapeutic product for the treatment of type 2 diabetes (T2D) is a long, resource-intensive process. Novel biomarkers could potentially aid clinical trial design by shortening clinical trials or enabling better prediction of at-risk populations and/or disease progression. Novel clinical trial designs could lead to reduced costs of development and less burden to patients, due to shorter trial duration, and/or less burdensome assessments.
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2. |
- Alsalim, Wathik, et al.
(författare)
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Insulin and incretin hormone responses to rapid versus slow ingestion of a standardized solid breakfast in healthy subjects.
- 2019
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Ingår i: Endocrinology, Diabetes & Metabolism. - : Wiley. - 2398-9238. ; 2:2, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- People with repeated rapid meal ingestion have been reported to have increased risk of insulin resistance, impaired glucose tolerance and obesity. To explore whether speed of eating a breakfast influences the postprandial rise of glucose, insulin and the incretin hormones, 24 healthy subjects (12 men and 12 women, mean age 62 years) ingested a standardized solid breakfast consisting of 524 kcal (60% from carbohydrate, 20% from protein, 20% from fat) over 5 or 12 minutes on separate days in random order. Breakfast ingestion increased circulating glucose and insulin with maximal levels seen at 30 minutes after start of meal ingestion with no significant difference in the two tests. Similarly, breakfast increased circulating levels of total (reflecting secretion) glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) with, again, no difference between the tests. Furthermore, gastric emptying, as revealed by the indirect paracetamol test, did not differ between the tests. We therefore conclude that the speed of breakfast ingestion does not affect the postprandial rise of glucose, insulin or incretin hormones in healthy subjects
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- Anderbro, Therese Carin, et al.
(författare)
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A longitudinal study of fear of hypoglycaemia in adults with type 1 diabetes
- 2018
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Ingår i: Endocrinology, Diabetes & Metabolism. - : Wiley. - 2398-9238 .- 2057-3316. ; 1:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate fear of hypoglycaemia (FoH) longitudinally in a cross‐sectional study of adult patients with type 1 diabetes. Specifically, we investigated two subgroups of patients who over 4 years either showed a substantial increase or decrease in level of FoH to identify factors associated with changes in FoH.Methods: The Swedish version of the Hypoglycaemia Fear Survey (HFS) along with a questionnaire to assess hypoglycaemia history was sent by mail to 764 patients in 2010. The responders in 2010 (n = 469) received another set of the same two questionnaires in 2014. HbA1c, insulin regimen, weight and creatinine from 2010 and 2014 were obtained from medical records. Those with an absolute difference in HFS scores ≥ 75th percentile were included in the subgroup analyses. Statistical analyses included one‐sample t tests, chi‐square and McNemar's test.Results: The absolute difference in the HFS total score (n = 347) between 2010 and 2014 was m = ±7.6, SD ± 6. In the increased FoH group, more patients reported a high level of moderate hypoglycaemic episodes as well as impaired awareness of hypoglycaemia in 2014 compared with the decreased FoH group. There were more subjects in the increased FoH group with insulin pumps in 2014 and in 2010. In the decreased FoH group, more patients had a high frequency of daily self‐monitoring of blood glucose (SMBG) in 2010 and in 2014.Conclusions: Fear of hypoglycaemia is stable across time for most patients. Changes in fear level are associated with changes in hypoglycaemia frequency. Thus, asking patients about changes in hypoglycaemia experiences is of great importance.
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- Baldimtsi, Evangelia, et al.
(författare)
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The role of chemokines in type 1 diabetes-associated neuropathy
- 2023
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Ingår i: Endocrinology, diabetes & metabolism. - : John Wiley & Sons. - 2398-9238. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To investigate whether circulating chemokines contribute to the development of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes (T1D).METHODS: Fifty-two patients with childhood-onset T1D (mean age 28 ± 4 yrs.; diabetes duration 19.5 ± 5.5 yrs.) and 19 control subjects (mean age 26.5 ± 4.5 yrs.) were included in a cross-sectional analysis of this long-term longitudinal cohort study. A subgroup of 24 patients was followed prospectively for a further 10 yrs. Plasma levels of Th1- (CXCL9, CXCL10 and CXCL11), Th2- (CCL17 and CCL22) and Th17-associated (CXCL8 and CCL20) chemokines were assessed in all subjects. Additionally, the TID patients underwent clinical examination and electroneurography.RESULTS: The frequency of neuropathy was 21% (11/52). Higher levels of CXCL9 levels were found in patients with DPN compared with control subjects (p = .019); by contrast, no difference between patients without DPN and control subjects was seen after adjustment for multiple comparisons. In patients with DPN, CXCL10 correlated negatively with suralis MCV and suralis SNAP (rho -0.966, p < .001 and rho -0.738, p < .001, respectively) and was positively correlated with the vibration perception threshold (rho 0.639, p = .034), while CXCL8 correlated negatively with the cold perception threshold (rho -0.645, p = .032). The frequency of neuropathy increased to 54% (13/24) in the subgroup of 23 TID patients, followed by an additional 10 yrs.CONCLUSIONS: Changes in Th1- and Th17-associated chemokines were associated with impaired peripheral sensory nerve function and nerve conduction after long disease duration in childhood-onset T1D.
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8. |
- Jarl, Gustav, 1978-, et al.
(författare)
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Comment on van Netten, et al : Definitions and criteria for diabetic foot disease
- 2020
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Ingår i: Endocrinology, Diabetes and Metabolism. - : John Wiley & Sons. - 2398-9238.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The International Working Group on the Diabetic Foot (IWGDF) recently published updated definitions for the diabetic foot field. However, the suggested definitions of lower limb amputations differ from the definitions of the International Organization of Standardization (ISO), which may create problems when implementing the definitions. This paper compares and discusses the amputation definitions of IWGDF and ISO.Results: Despite many similarities, the IWGDF and ISO systems have some important differences. First, the IWGDF uses the term “minor amputation” which is value-laden, arbitrary and has been defined in several different ways in the literature. Second, the IWGDF system lacks descriptions of amputations distal or through the ankle, which may increase the risk for misclassification. Third, hip disarticulations and transpelvic amputations are not included in the IWGDF system.Conclusion: It is suggested that future updates of the IWGDF definitions should be aligned with those of ISO, to meet the goal of global consensus on terminology related to lower limb amputation.
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9. |
- Lindgren, Ola, et al.
(författare)
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Consequences on islet and incretin hormone responses to dinner by omission of lunch in healthy men
- 2020
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Ingår i: Endocrinology, Diabetes & Metabolism. - : Wiley. - 2398-9238. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Omission of breakfast results in higher glucose and lower insulin and incretin hormone levels after both lunch and dinner. Whether omission of lunch has a similar impact on the following meal is not known. Aim: This study therefore explored whether omission of lunch ingestion affects glucose, islet and incretin hormones after dinner ingestion in healthy subjects. Materials & Methods: Twelve male volunteers (mean age 22 years, BMI 22.5 kg/m2) underwent two test days in random order with standard breakfast and dinner on both days with provision or omission of standard lunch in between. Results: The results showed that throughout the 300 minutes study period, glucose, insulin, glucagon and GIP levels after dinner ingestion did not differ between the two tests. In contrast, C-peptide, and GLP-1 levels were 26%-35% higher at later time points after dinner ingestion when lunch had been omitted (P <.05). Conclusion: We conclude that omission of lunch increases GLP-1 and insulin secretion and possibly also insulin clearance resulting in unchanged glucose and insulin levels after dinner ingestion.
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10. |
- Martinez, Maria Månsson, et al.
(författare)
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Beta cell function in participants with single or multiple islet autoantibodies at baseline in the TEDDY Family Prevention Study : TEFA
- 2021
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Ingår i: Endocrinology, Diabetes & Metabolism. - : Wiley. - 2398-9238. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the present study was to assess beta cell function based on an oral glucose tolerance test (OGTT) in participants with single islet autoantibody or an intravenous glucose tolerance test (IvGTT) in participants with multiple islet autoantibodies. Materials and methods: Healthy participants in Sweden and Finland, between 2 and 49.99 years of age previously identified as positive for a single (n = 30) autoantibody to either insulin, glutamic acid decarboxylase, islet antigen-2, zinc transporter 8 or islet cell antibodies or multiple autoantibodies (n = 46), were included. Participants positive for a single autoantibody underwent a 6-point OGTT while participants positive for multiple autoantibodies underwent an IvGTT. Glucose, insulin and C-peptide were measured from OGTT and IvGTT samples. Results: All participants positive for a single autoantibody had a normal glucose tolerance test with 120 minutes glucose below 7.70 mmol/L and HbA1c values within the normal range (<42 mmol/mol). Insulin responses to the glucose challenge on OGTT ranged between 13.0 and 143 mIU/L after 120 minutes with C-peptide values between 0.74 and 4.60 nmol/L. In Swedish participants, the first-phase insulin response (FPIR) on IvGTT was lower in those positive for three or more autoantibodies (n = 13; median 83.0 mIU/L; range 20.0-343) compared to those with two autoantibodies (n = 15; median 146 mIU/L; range 19.0-545; P =.0330). Conclusion: Participants positive for a single autoantibody appeared to have a normal beta cell function. Participants positive for three or more autoantibodies had a lower FPIR as compared to participants with two autoantibodies, supporting the view that their beta cell function had deteriorated.
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11. |
- Nyström, Thomas, et al.
(författare)
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Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin : A randomized, open, parallel-group study
- 2019
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Ingår i: Endocrinology, Diabetes & Metabolism. - : John Wiley & Sons. - 2398-9238. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV.Methods: This was a post hoc study whereas sixty-two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat-to-beat (NN) intervals (SDNN), was assessed by 24-hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF), low-frequency (LF) and very low-frequency power.Results: Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide-treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis.Conclusions: Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.
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12. |
- Persson, Frederik, et al.
(författare)
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Different patterns of second-line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic) : A multinational observational study.
- 2018
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Ingår i: Endocrinology, diabetes & metabolism. - : Wiley. - 2398-9238. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The understanding of second-line use of glucose-lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Our aim was to describe second-line GLD treatment patterns in four Nordic countries.Methods: All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second-line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second-line drug.Results: A rapid uptake of newer GLDs (GLP-1RA, DPP-4i and SGLT-2i) over the 10-year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second-line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7-fold greater in Sweden compared to Finland (49% vs 7%), and 1.6-fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively).Conclusions: Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second-line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.
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13. |
- Salami, Falastin, et al.
(författare)
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Complete blood counts with red blood cell determinants associate with reduced beta-cell function in seroconverted Swedish TEDDY children
- 2021
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Ingår i: Endocrinology, Diabetes and Metabolism. - : Wiley. - 2398-9238. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate whether changes in complete blood count (CBC) in islet autoantibody positive children with increased genetic risk for type 1 diabetes are associated with oral glucose tolerance tests (OGTT) and HbA1c over time. Methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study follows children with increased risk for type 1 diabetes in the United States, Germany, Sweden and Finland. In the current study, 89 Swedish TEDDY children (median age 8.8 years) positive for one or multiple islet autoantibodies were followed up to 5 (median 2.3) years for CBC, OGTT and HbA1c. A statistical mixed effect model was used to investigate the association between CBC and OGTT or HbA1c. Results: HbA1c over time increased by the number of autoantibodies (p <.001). Reduction in mean corpuscular haemoglobin (MCH) and mean cell volume (MCV) was both associated with an increase in HbA1c (p <.001). A reduction in red blood cell (RBC) counts (p =.003), haemoglobin (p =.002) and haematocrit (p =.006) levels was associated with increased fasting glucose. Increased red blood cells, haemoglobin, haematocrit and MCH but decreased levels of red blood cell distribution widths (RDW) were all associated with increased fasting insulin. Conclusions: The decrease in RBC indices with increasing HbA1c and the decrease in RBC and its parameters with increasing fasting glucose in seroconverted children may reflect an insidious deterioration in glucose metabolism associated with islet beta-cell autoimmunity.
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14. |
- Sjölin, Gabriel, 1979-, et al.
(författare)
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Treatment of patients with Graves' disease in Sweden compared to international surveys of an 'index patient'
- 2021
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Ingår i: Endocrinology, Diabetes & Metabolism. - : Wiley. - 2398-9238. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The treatment strategies for a 42-year-old female index patient with moderate Graves' disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. Materials and Methods From a Swedish cohort of 1186 GD patients (TT-12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This 'index patient cohort' was age 40-45, otherwise healthy female, with two children and uncomplicated GD. The applied first-line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT-12 cohort was also performed. Results In the 'Index cohort', 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (I-131). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where I-131 was preferred. The distribution of treatment in the TT-12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19-22) patients, as was RAI in old (age 69-73) patients. The age-related, but not the gender-related, cases differed significantly from the entire TT-12 cohort. Conclusion The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where I-131 is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from 'real life' has been presented and compared to treatment preferences of international thyroid association surveys.
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15. |
- Tavaglione, Federica, et al.
(författare)
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Human and molecular genetics shed lights on fatty liver disease and diabetes conundrum.
- 2020
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Ingår i: Endocrinology, diabetes & metabolism. - : Wiley. - 2398-9238. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- The causal role of abdominal overweight/obesity, insulin resistance and type 2 diabetes (T2D) on the risk of fatty liver disease (FLD) has robustly been proven. A consensus of experts has recently proposed the novel definition of 'metabolic dysfunction-associated fatty liver disease, MAFLD' instead of 'nonalcoholic fatty liver disease, NAFLD', emphasizing the central role of dysmetabolism in the disease pathogenesis. Conversely, a direct and independent contribution of FLD per se on risk of developing T2D is still a controversial topic. When dealing with FLD as a potential risk factor for T2D, it is straightforward to think of hepatic insulin resistance as the most relevant underlying mechanism. Emerging evidence supports genetic determinants of FLD (eg PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B13) as determinants of insulin resistance and T2D. However, recent studies highlighted that the key molecular mechanism of dysmetabolism is not fat accumulation per se but the degree of hepatic fibrosis (excess liver fat content-lipotoxicity), leading to reduced insulin clearance, insulin resistance and T2D. A consequence of these findings is that drugs that will ameliorate liver fat accumulation and fibrosis in principle may also exert a beneficial effect on insulin resistance and risk of T2D in individuals with FLD. Finally, initial findings show that these genetic factors might be directly implicated in modulating pancreatic beta-cell function, although future studies are needed to fully understand this relationship.
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- Turkmen, Sahruh, et al.
(författare)
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Neurosteroid involvement in threatened preterm labour
- 2021
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Ingår i: Endocrinology, Diabetes & Metabolism. - Sussex : John Wiley & Sons. - 2398-9238. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown.Methods: Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT).Results: Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p = .021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: −3.2, 95% confidence interval (CI): −5.5 to −0.9, p = .012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00–1.04, p = .038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r = .34, p = .044) and negatively with allopregnanolone (r = −.41, p = .013).Conclusions: Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist.
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