Incidence and risk factors of venous thromboembolism during postpartum period: a population-based cohort-study.

INTRODUCTION: The awareness of the incidence and timing of postpartum venous thromboembolic events guides the use of thromboprophylaxis. Our aims were to assess the incidence and mortality of venous thromboembolic events and identify its associated risk factors during different postpartum periods. MATERIAL AND METHODS: A population-based controlled cohort study by combining four large registers in 2001-2011. All women with a recent delivery were identified. The incidence, risk factors and mortality of venous thromboembolic events 0-180 days after delivery were assessed by using all healthy delivered women as the control group. The incidence was compared with that of the nonpregnant women. RESULTS: Among the 634 292 delivered women, 1169 had venous thromboembolic events 0-180 days postpartum. The incidence of venous thromboembolic events was highest during the first week postpartum: 37-fold compared with nonpregnant women, declining to two-fold immediately after that. Almost half of the venous thromboembolic events occurred between 43 and 180 days postpartum. The incidence of venous thromboembolic events was four-fold compared with that of nonpregnant women. Three venous thromboembolic events-related deaths occurred. Older age, higher body mass index, thrombophilia, multiple pregnancy, gestational diabetes, anemia, chorioamnionitis, threatening premature birth, in vitro fertilization with ovarian hyperstimulation, primiparity, cesarean section, cardiac/renal diseases, and varicose veins were associated with an increased risk for postpartum venous thromboembolic events. The risk remained elevated for 180 days in women with thrombophilia, cesarean section, multiple pregnancy, varicose veins, and cardiac disease. CONCLUSIONS: The risk of venous thromboembolic events remained elevated compared with that of the nonpregnant women after the usually defined postpartum period (6 weeks). The results might assist in selecting women in need of thromboprophylaxis.

Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL).

BACKGROUND: Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. METHODS: RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers.Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. DISCUSSION: To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age.

Metabolic syndrome is not associated with erectile dysfunction in apparently healthy men.

AIMS: To investigate whether metabolic syndrome (MetS) is associated with erectile dysfunction (ED) among apparently healthy men when depressive symptoms and serum testosterone levels are taken into account. METHODS: A study population of 549 men at risk for cardiovascular disease or type 2 diabetes was drawn from the participants of a population survey, the Harmonica Project. MetS was diagnosed with the United States National Cholesterol Education Program Third Adult Treatment Panel (ATPIII) 2005 definition, the International Diabetes Federation (IDF) 2005 definition and the Harmonization 2009 definition. ED was evaluated by the International Index of Erectile Function (IIEF-5) questionnaire. Depressive symptoms were assessed with Beck's Depression Inventory (BDI). RESULTS: Of the 549 men (mean age 58.4 ± 6.7 years), 56.5 % reported ED. The prevalence of MetS was 48.6%, 35.5%, and 50.6% according to the IDF, the ATPIII, and the Harmonization criteria, respectively. We found no difference in the prevalence of ED between men with or without MetS. In a multivariate analysis, age, presence of depressive symptoms and lower education were significant predictors of ED. CONCLUSIONS: The prevalence of ED is quite high even in apparently healthy men. Depressive symptoms are a critical component to consider in men suffering from ED.

Central sympatholytic therapy has anti-inflammatory properties in hypertensive postmenopausal women.

OBJECTIVE: Postmenopausal phase expresses many unfavourable physiological changes that lead to increased risk for cardiovascular disease. We compared the effect of two sympatholytic antihypertensive drug treatments, the centrally acting imidazoline receptor-1 agonist moxonidine and peripherally acting beta-blocking agent atenolol on sensitive inflammatory markers in overweight postmenopausal women with diastolic hypertension. METHODS: This was a multicentre, multinational double-blinded, prospective study comparing moxonidine (0.3 mg twice daily) with atenolol (50 mg once daily) in 87 hypertensive postmenopausal overweight women who were not taking hormone therapy. Sensitive C-reactive protein, IL-6, TNFalpha, TNFalpha-RII and adiponectin were determined in the beginning of the study and after 8 weeks of medical treatment. RESULTS: TNFalpha increased in atenolol and decreased in moxonidine group (P = 0.0004 between the groups). Adiponectin concentration decreased dramatically in atenonol but did not change in moxonidine treatment group (P < 0.0001 between the groups). In logistic regression analysis only treatment group showed an independent effect on changes in adiponectin and TNFalpha concentrations. CONCLUSION: We believe that centrally acting sympatholytic agent moxonidine is beneficial in the treatment of postmenopausal women with hypertension by reducing inflammatory cytokine TNFalpha without changing protective adiponectin level.

Does the hormone "endogenous ouabain" exist in the human circulation?

Studies in the early 1990s suggested that a hormone identical to ouabain or an isomer of ouabain is secreted by the adrenal glands into the circulation and plays a role in the regulation of arterial pressure and cardiac and renal function. This hormone, known as endogenous ouabain (EO), was claimed to contribute to the pathophysiology of a number of disorders including heart failure, renal failure, pregnancy-induced, and essential hypertension. However, some research groups have been unable to confirm the presence of EO in the human circulation and the issue remains in dispute. In that the implications are of considerable importance to clinicians who, like the authors, lack biochemical expertise, it would be useful if the dispute could be addressed by disinterested scientists with long-standing and acknowledged expertise in analytical chemistry who could opine as to whether the evidence is, or is not, sufficient to state categorically that EO does (or does not) exist in the circulation in man. This brief review does not present new data but, rather, recommends that adjudication is needed regarding this important issue. © 2018 BioFactors, 44(3):219-221, 2018.

Insulin resistance and sympathetic overactivity in women.

Insulin sensitivity decreases for the first time in females at the time of menarche. A much more profound decrease in insulin sensitivity is observed at the end of pregnancy. This physiological insulin resistance is not accompanied by a rise in overall sympathetic activity as reflected in plasma noradrenaline levels, but there is evidence of moderate sympathetic overactivity in muscle and the heart. Pre-eclampsia is characterized by increased insulin resistance, sympathetic overactivity and a particular lipid profile. Thus it is the first manifestation of metabolic syndrome. Women with a history of pre-eclampsia have persistent insulin resistance after pregnancy associated with increased sympathetic activity of the cardiovascular system, and coronary artery disease later in life. Aging is accompanied by a greater increase in sympathetic traffic in women than in men, and inflammation (measured via C-reactive protein) seems to be more strongly related to metabolic syndrome in women than in men. The clinical relevance of these observations remains to be shown. As the key factors of metabolic syndrome, such as insulin resistance and sympathetic overactivity, are closely inter-related, treatment should be aimed at cutting the vicious circle at many points: lifestyle modification (diet, increasing exercise) as a basis of therapy, use of insulin sensitizers (e.g. metformin) to decrease insulin resistance, central sympatholytics (e.g. moxonidine), and AT-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors to overcome sympathetic overactivity, hypertension and inflammation.

Impaired vascular dilatation in women with a history of pre-eclampsia.

OBJECTIVE: The mechanisms underlying increased cardiovascular risk among women with a history of pre-eclampsia remain unclear. Impaired endothelial function has been observed in both pre-eclampsia and atherosclerosis, and provides a plausible link between the two conditions. We studied endothelial function and arterial compliance in non-pregnant, previously pre-eclamptic women. DESIGN: A study of 30 women with a history of pre-eclampsia and 21 women with a previous normotensive, uncomplicated pregnancy was carried out. METHODS: Changes in brachial artery blood flow, induced by intra-arterial infusions of an endothelium-independent (sodium nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were measured by venous occlusion plethysmography. Arterial stiffness was assessed by pulse-wave analysis. RESULTS: Vasodilatation was impaired in women with previous pre-eclampsia; at low and high concentrations of endothelium-independent (P = 0.004 and P = 0.057, respectively) and endothelium-dependent (P = 0.045 and P = 0.02) vasodilators, respectively. There was no difference in arterial stiffness between the groups (P = 0.45). In multiple regression analyses both endothelium-independent and endothelium-dependent vasodilatations were independently associated with a history of pre-eclampsia and parity. There was no correlation with blood pressure, body mass index (BMI), smoking or age. CONCLUSIONS: The finding of impaired vascular dilatation several years after a pre-eclamptic pregnancy could contribute to the higher risk of cardiovascular disease in these women.

Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial.

OBJECTIVE: To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS: Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m(2) were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40-0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (-0.58 kg [95% CI -1.12 to -0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS: A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy.

AIMS/HYPOTHESIS: To find out whether the levels of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), highly phosphorylated IGFBP-1 (hpIGFBP-1), and IGF binding protein-3 (IGFBP-3) are related to the progression of diabetic retinopathy (DR) during pregnancy and postpartum. METHODS: In a prospective study of 42 pregnant women with Type 1 diabetes and 9 nondiabetic controls, DR was graded from fundus photographs. Levels of serum total IGF-I and two different phosphoisoform patterns of IGFBP-1 and IGFBP-3 were measured during the first and third trimester of pregnancy and 3 months postpartum. RESULTS: Both the levels of serum total IGF-I (P<.0001) and IGFBP-3 (P=.003) were lower in the diabetic than in the nondiabetic women during pregnancy and postpartum (repeated-measures ANOVA between the groups). Additionally, the IGF-I and IGFBP-3 levels tended to be lower in the diabetic women with more severe DR at baseline than in those with less severe DR. There were no statistically significant differences in the levels of IGF-I and IGFBP-3 in the diabetic women with progression of DR compared with those without. No statistical differences appeared in the IGFBP-1 phosphoisoform patterns between the groups. CONCLUSIONS/INTERPRETATION: In diabetic women, mean serum levels of IGF-1 and IGFBP-3 are lower than in nondiabetic controls during pregnancy and/or postpartum. Because there was no clear connection between the IGF system and progression of DR during pregnancy, it is unlikely that these substances mediate the tendency of DR to progress during pregnancy.

50gram oral glucose challenge test combined with risk factor-based screening for gestational diabetes.

OBJECTIVE: Our aim was to study whether universal screening of all pregnant women by Oral Glucose Challenge Test (OGCT) would identify a higher number of women with Gestational Diabetes (GDM) than risk factor based screening. STUDY DESIGN: A 50 g OGCT test was performed prospectively in 532 unselected women at 26-28 weeks of gestation. The 1-h venous plasma glucose concentration of >7.3 mmol/l was considered as a positive screening result. Patients with a positive OGCT underwent a 75 g 2-h OGTT, which was used as the actual diagnostic test for GDM. When two or all three of the glucose concentrations in OGTT (measured at fasting state and 1 and 2 h after the 75 g glucose load) were above the 97.5th percentile the patient was considered as having GDM. In addition, women with risk factors for GDM also underwent a 75 g OGTT regardless of the result of the OGCT. RESULTS: A positive 50 g OGCT was obtained in 123 (23%) of the women. In 15 (12%) of these, a diagnosis of GDM was established by the subsequent OGTT. Out of the 409 remaining women with a normal OGCT, 148 (36%) had risk factors for GDM. An OGTT performed in these patients identified 4 additional women with a GDM. Seventy-nine percent of GDM was thus found with 50g OGCT without regarding risk factors. Forty-seven percent of the women with GDM would have been missed in screening by risk factors only. CONCLUSIONS: In our population 50 g OGCT appears to identify a higher number of GDM than risk factor based screening. Combined with risk factor screening a few more cases of GDM would be found.

Manifestations of chronic disease during pregnancy.

CONTEXT: Physiologic changes of pregnancy include insulin resistance, thrombophilia, immunosuppression, and hypervolemia. These changes may herald the development of disease in later life. OBJECTIVE: To summarize current evidence on how pregnancy reveals risk of chronic disease. EVIDENCE ACQUISITION: MEDLINE was searched for articles published between 1990 and 2005 relating pregnancy conditions to the development of chronic disease. Bibliographies and the Web sites of the International Society of Obstetric Medicine and International Society for the Study of Hypertension in Pregnancy were also reviewed. EVIDENCE SYNTHESIS: Pregnancy exaggerates atherogeniclike responses, including insulin resistance and dyslipidemia, manifesting as preeclampsia or gestational diabetes. These complications herald an increased risk of postpartum cardiovascular disease, with a 2-fold increased risk of coronary artery disease and stroke. Women with gestational diabetes mellitus can progress to type 2 diabetes mellitus. The rate of progression varies from 6% to 92% depending on diagnostic criteria, race/ethnicity, and duration of surveillance (from 6 months to 28 years). Pregnancy increases risk of venous thrombosis by 7- to 10-fold. Heritable thrombophilia is present in at least 15% of Western populations and underlies at least 50% of gestational venous thromboses. Thus, the procoagulant changes during pregnancy can unmask hereditary thrombophilia. An important adaptation leading to immunotolerance of the fetoplacental unit is a switch from helper T-cell (T(H)) 1 dominance to T(H)2 dominance. Patients with a T(H)1-dominant immune disease, such as rheumatoid arthritis or multiple sclerosis, improve during pregnancy. However, rheumatoid arthritis is 5 times more likely to develop after delivery than at any other time. During pregnancy, there is a 50% increase in plasma volume, which can unmask glomerulopathies, peripartum cardiomyopathy, arterial aneurysms, or arteriovenous malformations. Development of intrahepatic cholestasis of pregnancy predicts increased risk of later cholelithiasis. CONCLUSIONS: The physiologic changes of pregnancy can reveal risk of chronic diseases. Exaggerated responses reflective of the metabolic syndrome are seen in preeclampsia and gestational diabetes and can herald future cardiovascular and metabolic disease. Pregnancy is therefore an important screening opportunity for cardiovascular and metabolic disease risk factors, with the possibility of early intervention.

The incidence and risk factors of recurrent venous thromboembolism during pregnancy.

INTRODUCTION: Recurrent venous thromboembolism (VTE) during pregnancy is a challenging topic with relatively few publications. The aim of this study was to identify the incidence and the risk factors of recurrent antepartum VTE in women with a history of at least one previous VTE episode. MATERIALS AND METHODS: This observational cohort study involved 270 pregnant women (369 pregnancies) with at least one previous episode of VTE. The risk factors of recurrent antepartum VTE were identified by using group A (women without recurrent venous thromboembolism VTE) as a control group for group B (women with recurrent VTE despite LMWH (low molecular weight heparin) prophylaxis) and C (women with VTE recurrence in early pregnancy before the planned initiation of LMWH prophylaxis). RESULTS AND CONCLUSIONS: The incidence of recurrent VTE was 7.6% (n=28). Twelve recurrent VTEs in ten women (3.3%) developed during early pregnancy before initiation of LMWH and sixteen recurrent VTEs (4.3%) developed in 15 women despite LMWH prophylaxis. In women with recurrent antepartum VTE, the incidence of a history of two or more previous VTEs (group A vs. B: 5.7% vs. 40.0%, p<0.001; group A vs. C: 5.7% vs. 30.0%, p=0.022), previous VTE in connection with antiphospholipid antibody syndrome (group A vs. B: 2.6% vs. 20.0%, p=0.012) and a history of VTE related to hormonal risk factors (group A vs. B: 60.4% vs. 93.3%, p=0.011) was significantly higher compared to those with successful LMWH-prophylaxis. The percentage of the women with long-term anticoagulation was also significantly higher among the women with recurrent antepartum VTE (group A vs. B: 7.6% vs. 46.7%, p<0.001) compared to those with successful LMWH-prophylaxis. The risk of antepartum recurrent VTE is considerable in women with a history of two or more previous VTEs, antiphospholipid antibody syndrome or long-term anticoagulation. The antepartum prophylaxis with prophylactic dose of LMWH or even with intermediate dose of LMWH might not be sufficient in this high-risk population.

Elevated serum angiopoietin-like protein 6 in women with subsequent pregnancy-induced hypertension: a preliminary study.

OBJECTIVE: Association of maternal angiopoietin-like protein 6 (Angptl6) levels with subsequent development of pregnancy-induced hypertension (PIH). METHODS: At 24 and 32 weeks of gestation in 47 relatively overweight (BMI ≥ 24 kg/m(2)), nulliparous pregnant women serum concentrations of Angptl6 were quantified prospectively. Insulin sensitivity and lipids were measured at 24 weeks. RESULTS: Angptl6 levels at 24 weeks, but not at 32 weeks, were significantly higher in women with subsequent PIH. Metabolic factors at 24 weeks did not correlate with Angptl6 levels. CONCLUSION: This preliminary study suggests that in the second trimester, Angptl6 levels are higher in women with subsequent PIH.

Safety of low-molecular-weight heparin during pregnancy: a retrospective controlled cohort study.

OBJECTIVE: To study the safety of low-molecular-weight heparin (LMWH) treatment during pregnancy for the mother and the foetus. STUDY DESIGN: Retrospective controlled cohort study. Six hundred and forty-eight pregnancies exposed to LMWH were compared with 626 unexposed pregnancies. Principal characteristics, indications for LMWH use, and maternal and foetal complications were reported for each pregnancy. Data were obtained from patients' electronic hospital records and analysed using Statistical Package for the Social Sciences Version 17.0. RESULTS: The incidence rates of various pregnancy complications did not differ between the groups (LMWH group vs control group): 1.56% vs 1.1% for thrombocytopenia, 8.7% vs 6.5% for preterm delivery, 0.7% vs 0.3% for stillbirth, 1.4% vs 1.0% for severe pre-eclampsia, 2.7% vs 2.2% for foetal growth restriction, and 10.7% vs 7.8% for antenatal bleeding. One serious antenatal maternal haemorrhage occurred in the LMWH group (0.15%), but this was unrelated to LMWH use. The caesarean section rate and the amount of bleeding during delivery were similar in the two groups (21% vs 19% and 500 vs 450 ml, respectively). The risk of major blood loss during labour (>1000 ml) was no higher in the LMWH group compared with the control group. The incidence of allergic skin reactions was 0.3% in the LMWH group. No heparin-induced thrombocytopenia or symptomatic osteoporotic fractures were observed. Recurrent venous thromboembolic events occurred in 2.5% of patients in the LMWH group. CONCLUSION: This study indicates that the use of LMWH is safe during pregnancy.

Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial.

Recurrent miscarriage affects 1-2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment. A randomised double-blind (for aspirin) multicentre trial was performed among 207 women with three or more consecutive first trimester (<13 weeks) miscarriages, two or more second trimester (13-24 weeks) miscarriages or one third trimester fetal loss combined with one first trimester miscarriage. Women were analysed for thrombophilia. After complete work-up, women were randomly allocated before seven weeks' gestation to either enoxaparin 40 mg and placebo (n=68), enoxaparin 40 mg and aspirin 100 mg (n=63) or aspirin 100 mg (n=76). The primary outcome was live-birth rate. Secondary outcomes were pregnancy complications, neonatal outcome and adverse effects. The trial was ended prematurely because of slow recruitment. A live birth rate of 71% [relative risk (RR) 1.17, 95% confidence interval (CI) 0.92-1.48] was found for enoxaparin and placebo and 65% [RR 1.08, 95% CI 0.83-1.39] for enoxaparin and aspirin when compared to aspirin alone (61%, reference group). In the whole study group the live birth rate was 65% (95% CI 58.66-71.74) for women with three or more miscarriages (n=204). No difference in pregnancy complications, neonatal outcome or adverse effects was observed. No significant difference in live birth rate was found with enoxaparin treatment versus aspirin or a combination of both versus aspirin in women with recurrent miscarriage.

Metabolic syndrome and the menopause.

The metabolic syndrome consists of a combination of risk factors that include abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance. It increases the risk of cardiovascular disease and type 2 diabetes. The increased risk of cardiovascular disease is higher in women than in men. The first manifestation of metabolic syndrome may occur in pregnancy presenting as gestational diabetes or preeclampsia. Both conditions are associated with increased insulin resistance. Also metabolic syndrome is more common in polycystic ovarian syndrome. It has been suggested that there is a metabolic syndrome resulting from the menopause due to estrogen deficiency, as many of the risk factors are more prevalent in postmenopausal women. Also estrogen replacement improves insulin sensitivity and reduces the risk of diabetes. The key elements in managing the metabolic syndrome are weight reduction, increasing physical activity and diet modification. If blood pressure, lipid and glycaemic control are not achieved through these interventions then pharmacological therapy will be required.

A relationship between insulin sensitivity and vasodilation in women with a history of preeclamptic pregnancy.

Women with a history of preeclampsia are characterized by vascular dysfunction and an increased risk of cardiovascular disease. In the present study we investigated whether insulin sensitivity is decreased in women with previous preeclampsia and whether it is associated with endothelium-dependent and/or -independent vasodilation and/or features of metabolic syndrome. Twenty-eight nonobese women with previous severe preeclampsia and 20 women with a previous normotensive pregnancy were studied 5 to 6 years after the index pregnancy. Vasodilation was measured by venous occlusion plethysmography after intra-arterial infusions of sodium nitroprusside and acetylcholine and insulin sensitivity by the intravenous glucose tolerance test using the minimal model technique. The women were tested for lipid profile, inflammatory status and endothelial activation. Insulin sensitivity did not differ between the groups (P=0.24). Insulin sensitivity correlated positively to endothelium-dependent vasodilation only in the patient group in both low (beta=0.59; P=0.04) and high (beta=0.53; P=0.04) concentrations of acetylcholine and in a high concentration of sodium nitroprusside (beta=0.0007; P=0.006). In multivariate analysis, the waist/hip ratio (P=0.04) and serum triglycerides (P=0.04) had the most effect on insulin sensitivity in the patient group. Gestational weeks at the onset of preeclamptic hypertension (P=0.02) and proteinuria (P=0.02) associated positively with insulin sensitivity together with first-trimester body mass index (P=0.008) and maximum diastolic blood pressure during preeclampsia (P=0.005). The present study indicates a relation between insulin sensitivity with vascular dilatory function in women with previous preeclampsia. Furthermore, early onset preeclampsia correlates with impaired insulin sensitivity later in life.

Glycodelin: a novel serum anti-inflammatory marker in type 1 diabetic retinopathy during pregnancy.

PURPOSE: Inflammation may play a role in the development of diabetic retinopathy during pregnancy. Glycodelin is a glycoprotein whose secretion from the endometrial glands increases during pregnancy. Glycodelin has immunosuppressive properties thought to play a role in the protection of the fetoplacental unit. We studied the role of glycodelin in the development and progression of retinopathy in type 1 diabetes during pregnancy. METHODS: Retinopathy was graded from fundus photographs in 45 diabetes subjects and nine non-diabetes subjects prospectively during pregnancy. Serum glycodelin concentration was measured by an immunofluorometric assay. RESULTS: In women with diabetes with progression of retinopathy, serum glycodelin concentration was 263 ng/ml (range 116-505 ng/ml) during the first trimester, 61 ng/ml (range 30-106 ng/ml) during the second trimester, and 29 ng/ml (range 13-53 ng/ml) during the third trimester, compared with values of 595 ng/ml (range 376-870 ng/ml), 104 ng/ml (range 75-228 ng/ml) and 45 ng/ml (range 32-74 ng/ml), respectively, in diabetes subjects without progression (p = 0.005 between the groups). Low glycodelin concentration was associated with progression of diabetic retinopathy in multiple regression analysis. Serum glycodelin concentration was similar in women with and without diabetes throughout pregnancy (p = 0.63 by repeated measures ANOVA). CONCLUSIONS: Low glycodelin concentration is associated with progression of retinopathy in pregnant women with diabetes. A possible causal relationship between low glycodelin levels and progression of retinopathy may be mediated by the immunomodulatory properties of glycodelin.