Subclinical inflammation associated with prolonged TIMP-1 upregulation and arterial stiffness after gestational diabetes mellitus: a hospital-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. METHODS: We studied two cohorts-120 women with a history of GDM and 120 controls-on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. RESULTS: PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women compared with non-obese ones. CONCLUSIONS: PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.

Oxidized LDL, insulin resistance and central blood pressure after gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is an indicator of future cardiovascular disease. We investigated whether sensitive biomarkers of increased cardiovascular risk differ between women with and without a history of GDM few years after pregnancy, and whether obesity affects the results. MATERIAL AND METHODS: We studied two cohorts - 120 women with a history of GDM and 120 controls, on average 3.7 years after delivery. Circulating concentrations of oxidized low-density lipoprotein (oxLDL) were determined by ELISA. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to estimate insulin resistance. Central blood pressure (cBP) was measured noninvasively from a radial artery pulse wave. The primary outcomes were possible differences in oxLDL, HOMA-IR or cBP between the groups. Secondly, we investigated the influence of obesity on the results, also using adjusted multiple linear regression analyses. RESULTS: OxLDL concentrations or cBP did not differ between the two cohorts, but HOMA-IR was significantly higher in women with previous GDM than in controls, 1.3 ± 0.9 (SD) and 1.1 ± 0.9, respectively (p = 0.022). In subgroup analyses, HOMA-IR (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) cBP were significantly higher in obese subgroups compared with non-obese ones. Body mass index was an important determinant of HOMA-IR and cBP in multiple linear regression analyses. CONCLUSIONS: Over 3 years after delivery, women with GDM were still more insulin-resistant than controls. Obesity turned out to be a more important determinant of insulin resistance and cBP compared with GDM.

Clinical features of preeclampsia and hypertensive disorders in pregnancies after different frozen embryo transfer regimens.

OBJECTIVES: To compare whether the clinical features of preeclampsia (PE) or gestational hypertension (GH) were different in pregnancies after a frozen embryo transfer (FET), depending on the FET regimen used. STUDY DESIGN: A retrospective study including 58 pregnancies with PE and 64 pregnancies with GH, all with singleton live births. Pregnancies were stratified according to the presence or absence of a corpus luteum (CL). MAIN OUTCOME MEASURES: Clinical characteristics of PE and GH, maternal background factors, postpartum hemorrhage (PPH), key perinatal outcomes. RESULTS: Among PE patients, no difference was found in the clinical characteristics and in the maternal background factors, when comparing women with a CL to women without a CL. PE patients in the group without a CL had a hemorrhage of > 500 mL or > 1000 mL significantly more often than patients with a CL. Multivariable analyses confirmed this risk. Perinatal outcomes were similar. Among GH patients, there was no difference in the clinical features and maternal background factors, when comparing CL cycles to cycles without a CL. The amount of PPH was higher among the patients without a CL, but the frequency of a > 500 mL or > 1000 mL hemorrhage was similar between groups. No risk increase was seen in multivariable analyses. CONCLUSIONS: Among FET patients with PE, the risk of PPH wasincreased in pregnancies after cycles without a CL, compared to cycles with a CL. The presence or absence of a CL did noteffectthe severity of PE and GH, the duration of pregnancy or blood pressure levels.

Risk assessment of hypertensive disorders of pregnancy and other adverse pregnancy outcomes after frozen embryo transfers following an artificial cycle: A retrospective cohort study.

OBJECTIVES: The primary aim was to investigate if frozen embryo transfer (FET) without a corpus luteum increases the risk of hypertensive disorders of pregnancy (HDP). The secondary aim was to investigate other adverse maternal and perinatal outcomes. METHODS: This was a retrospective cohort study of 1168 singleton pregnancies and live births following a FET with either an artificial cycle (AC-FET) (n = 631) or a natural/modified natural/stimulated cycle (CL-FET) (n = 537) between 2012 and 2020. The data were collected from patient records. The primary outcome was HDP. Secondary outcomes included cesarean sections, placental retention problems, postpartum hemorrhage (PPH), the duration of pregnancy, birth weight, low birth weight, macrosomia, length of gestation, preterm birth, small for gestational age, and large for gestational age. RESULTS: In the AC-FET group, there was an increased incidence of pre-eclampsia, gestational hypertension, cesarean sections, PPH over 500 and 1000 mL, and retained placental tissue, compared with the CL-FET group. These associations remained significant in logistic regression analyses with clinically relevant adjustments. CONCLUSION: The risk of HDP and several other maternal complications seems to be increased after AC-FET compared with CL-FET. Our findings support most earlier studies regarding HDP and add to the knowledge on other maternal and perinatal risks involved in AC-FET, including an increased risk of milder forms of placental retention. More studies are needed to confirm these findings.

Mitochondrial DNA variant m.15218A > G in Finnish epilepsy patients who have maternal relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus.

BACKGROUND: Mitochondrial diseases caused by mutations in mitochondrial DNA (mtDNA) affect tissues with high energy demand. Epilepsy is one of the manifestations of mitochondrial dysfunction when the brain is affected. We have studied here 79 Finnish patients with epilepsy and who have maternal first- or second-degree relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus. METHODS: The entire mtDNA was studied by using conformation sensitive gel electrophoresis and PCR fragments that differed in mobility were directly sequenced. RESULTS: We found a common nonsynonymous variant m.15218A > G (p.T158A, MTCYB) that occurs in haplogroup U5a1 to be more frequent in patients with epilepsy. The m.15218A > G variant was present in five patients with epilepsy and in four out of 403 population controls (p = 0.0077). This variant was present in two branches in the phylogenetic network constructed on the basis of mtDNA variation among the patients. Three algorithms predicted that m.15218A > G is damaging in effect. CONCLUSIONS: We suggest that the m.15218A > G variant is mildly deleterious and that mtDNA involvement should be considered in patients with epilepsy and who have a maternal history of epilepsy, sensorineural hearing impairment or diabetes mellitus.

Arterial stiffness in fertile women with metabolic syndrome.

INTRODUCTION: Although metabolic syndrome (MetS) is evidently associated with the risk of cardiovascular disease (CVD), recently its use has been questioned. We studied the utility of MetS diagnosis when estimating individual CVD risk. METHODS: We compared 27 fertile women with MetS and 27 counterparts without the syndrome, matched pairwise according to well-known risk factors of CVD. Pulse wave velocity (PWV) and central blood pressure (cBP) were determined noninvasively via a SphygmoCor device. Arterial compliance was measured noninvasively with an HDI/PulseWaveTMCR-2000 arterial tonometer. RESULTS: PWV (7.1 ± 2.5 versus 6.5 ± 1.1 m/s, p = .037), and both systolic (120.9 ± 12.2 versus 111.5 ± 16.0 mmHg, p = .031) and diastolic cBP (81.3 ± 8.5 versus 74.1 ± 11.2 mmHg, p = .035) were higher in the MetS group. Systemic arterial compliance values were lower in both large (15.1 ± 8.0 versus 16.1 ± 4.4 mL/mmHg × 10, p = .034) and small arteries (7.1 ± 2.5 versus 9.3 ± 3.2 mL/mmHg ×100, p = .010) in women with MetS. CONCLUSIONS: Fertile women with MetS had increased arterial stiffness, as measured by three different methods. Our results highlight the utility of MetS when revealing increased individual CVD risks in fertile-aged women. Key messages Women with MetS have increased arterial stiffness when measured by different methods. MetS is a useful clinical tool to assess increased cardiovascular risk, particularly among fertile-aged women.

The risk of metabolic syndrome after gestational diabetes mellitus - a hospital-based cohort study.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at an increased risk of developing metabolic syndrome (MetS) after delivery. Recently, the prevalence of both GDM and MetS has increased worldwide, in parallel with obesity. We investigated whether the presentation of MetS and its clinical features among women with previous GDM differs from that among those with normal glucose tolerance during pregnancy, and whether excess body weight affects the results. METHODS: This hospital-based study of two cohorts was performed in Kanta-Häme Central Hospital, Finland. 120 women with a history of GDM and 120 women with a history of normal glucose metabolism during pregnancy, all aged between 25 and 46 were enrolled. They all underwent physical examination and had baseline blood samples taken. All 240 women were also included in subgroup analyses to study the effect of excess body weight on the results. RESULTS: Although the groups did not differ in body mass index (BMI; p = 0.069), the risk of developing MetS after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 19 vs. 8 cases (p  =  0.039). Fasting glucose (p < 0.001) and triglyceride levels (p < 0.001) were significantly higher in women affected. In subgroup analysis, cardiovascular risk factors were more common in participants with high BMI than in those with previous gestational diabetes. CONCLUSIONS: The risk of MetS was 2.4-fold higher after GDM than after normal pregnancy. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM. Multivariate analysis supported the main findings. Weight control is important in preventing MetS after delivery.