Could serum levels of irisin be used in gestational diabetes predicting?

ObjectiveGestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy leading to acute and chronic complications in both mother and newborn. The pathogenesis of GDM has not been fully understood, However, since the disease shares risk factors with type 2 diabetes mellitus (T2DM), a relationship between these two disease states is plausible. The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate the relationship between irisin levels and gestational diabetes mellitus and the possible benefits of the metabolic profile.Materials and methodsWe performed a cross-sectional analysis of circulating levels of irisin in 100 pregnant women similar for age and body mass index and the groups included 50 gestational diabetic patients and 50 healthy pregnant volunteers. Serum irisin levels were measured by ELISA kit.ResultsMean age and body mass index levels were similar in both groups. Median HbA1c, fasting blood glucose, Glucose 1 h, Glucose 2 h and fasting insülin levels were higher in with gestational diabetic patients compared to the control group. In gestational diabetic group, the median irisin level was lower than in the control group.ConclusionSerum irisin levels were lower in gestational diabetic patients. Further investigations are needed to explore the underlying biological effects of irisin on pregnant women.     

Pregnancy outcomes in women aged 35 years or older with gestational diabetes – a registry-based study in Finland

Objective: To compare pregnancy outcomes of women ≥35 years to women <35 years with and without gestational diabetes.

Methods: The data include 230?003 women <35 years and 53?321 women ≥35 years and their newborns from 2004 to 2008. In multivariate modeling, the main outcome measures were preterm delivery (<28, 28–31 and 32–36 weeks' gestation), Apgar scores <7 at 5?min, small for gestational age (SGA), fetal death, asphyxia, preeclampsia, admission to neonatal intensive care unit (NICU), shoulder dystocia and large for gestational age (LGA).

Results: In comparison to women <35 with normal glucose tolerance, preeclampsia (OR 1.57, CI 1.30–1.88), admission to the NICU (OR 3.30, CI 2.94–3.69) and shoulder dystocia (OR 2.12, CI 1.05–4.30) were highest in insulin-treated women ≥35 years. In women ≥35, diet- and insulin-treated gestational diabetes mellitus (GDM) increased the rates of preeclampsia, shoulder dystocia and admission to NICU (OR 3.07 CI 2.73–3.45). The effect of advanced maternal age was observed in very preterm delivery (<28 weeks), fetal death, preeclampsia and NICU. The increase in preeclampsia was statistically significant.

Conclusions: GDM at advanced age is a high risk state and, more specifically, the risk caused by age and GDM appear to be increasing in preeclampsia.     

Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes – is recommended weight gain too liberal?

This is a retrospective cohort study of women with GDM treated with glucose-lowering agents that were followed and gave birth between 2005 and 2015 in the Assaf Harofeh medical center, Israel. Classification and regression tree method identified four groups according to adverse outcomes, consisted of 74 women with pre-gestational BMI below 25, 98 women with BMI 25–31, 90 women 31–39 and 18 women above 39. Respectively, median GWG was 12?kg (8–16), 11?kg (8–15), 7.5?kg (3.75–11) and 5?kg (–1.5 to 11.5) (p?<?.001). The risk for composite adverse outcomes was higher in the groups of BMI 25–31 (73.5%) and 31–39 (83.3%) in comparison to BMI <25 (51.4%) and 39?<?(55.6%), p?<?.001. In women with pre-gestational BMI of <25, GWG of more than the median resulted in odds ratio of 2.75 (1.07–7.08, p?=?.036) for adverse pregnancy outcomes compared with participants who gained less than the median. Maternal obesity is related to adverse pregnancy outcomes. Women with GDM with normal pre-gestational BMI who gained weight according to IOM recommendations still experienced adverse outcomes.     

Screening of gestational diabetes mellitus: a new consensus?

The choice of thresholds to diagnose gestational diabetes mellitus (GDM) is a topic of ongoing controversy. In 2008, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study showed continuous graded relationships between increasing maternal plasma glucose and increasing frequency of adverse perinatal outcomes. Macrosomia (birth weight>90th percentile for gestational age), primary cesarean delivery, clinical neonatal hypoglycemia and hyperinsulinemia (cord serum C peptide>90th percentile) were all related to each of the 3 glucose values (fasting plasma glucose and at 1 and 2 hours after the 75 g oral glucose test). The associations were continuous with no obvious thresholds at which risks increased. The International Association of Diabetes and Pregnancy Study Group (IADPSG) recently issued recommendations that the diagnosis of GDM be made when any of the following thresholds are met or exceeded: fasting plasma glucose: 0,92 g/L; 1 hour: 1,80 g/L; or 2 hours: 1,53 g/L after the 75 g oral glucose test. These criteria were chosen to identify pregnancy with increased risk of adverse perinatal outcomes. By the new criteria, the total incidence of gestational diabetes in the HAPO population was 17, 8%. Fasting plasma glucose (FPG) in early pregnancy appears as an important predictive factor. Higher first trimester FPG (lower than those diagnostic of diabetes) are associated with increased risks of later diagnosis of gestational diabetes and adverse pregnancy outcomes. Whether this new consensus will be adopted by public health bodies and professionals remains to be seen.     

Can we predict the need for pharmacological treatment according to demographic and clinical characteristics in gestational diabetes?

Objective: To determine the ability to predict the need for pharmacological treatment in gestational diabetes mellitus (GDM).

Method: A retrospective cohort study. Data were collected from medical records of 1324 GDM patients including demographic data, family history of diabetes, obstetrical history, laboratory results, treatment modality and level of glycemic control. Patients who were identified as pre-gestational diabetes were excluded.

Results: Overall, 143 (10.8%) GDM patients required pharmacological therapy. Of women who had GDM in their previous pregnancy; only 11.65% achieved desired glycemic control solely by diet treatment. Moreover, 62.5% of patients requiring pharmacological therapy in their previous pregnancy achieved desired level of glycemic control only by diet. Of patients who achieved desired level of glycemic control on diet until the second antenatal visit, 95% continued to maintain desired level glycemic control throughout pregnancy. Pre-pregnancy BMI?>30, fasting plasma glucose >95?mg/dL and maternal age above 30 were associated with increase need for pharmacological treatment. One abnormal value in the OGTT and GCT result >2?mg/dL did not predict the need for pharmacological therapy. Primigravida and family history of GDM were not found to be predictors for treatment modality.

Conclusion: Using clinical and demographical data can predict the need for pharmacological treatment for GDM.     

Concurrence of gestational diabetes and pre-gravid obesity (“diabesity”) in twin gestations

Objective: To assess the effect of the concurrence of gestational diabetes mellitus (GDM) and pre-gravid obesity in twin gestations (“diabesity”).

Methods: We compared perinatal outcomes of twin gestation in mothers with GDM and pre-gravid obesity (1.7%), mothers with GDM but with normal BMI (6.2%), and obese mothers without GDM (7.0%).

Results: Twin pregnancies with “diabesity” were associated with significantly higher incidence of stillbirth (OR = 6.4; 95%CI = 1.4, 33.4) and existing chronic hypertension (OR = 4.2; 95%CI = 1.2, 14.8) than in GDM pregnancies without obesity, and with births at 33–36 weeks as compared with the other groups. Otherwise, the comparisons showed remarkable similar results in terms of gestational age, birth weight, preeclampsia, cesarean section rate, and fetal-neonatal outcomes.

Conclusion: It appears that diabesity has a relatively minor effect in twins. If this will be confirmed by other studies, it would be important to elucidate how twins ameliorate the adverse outcomes of diabesity.     

Association between pregnancy-associated plasma protein-A and gestational diabetes requiring insulin treatment at 11–14 weeks of gestation

Objective: To evaluate whether gestational diabetes mellitus (GDM) requiring insulin treatment (White’s classification A2) is associated with an alteration of pregnancy-associated plasma protein-A (PAPP-A) serum levels at first-trimester screening between 11 and 14 weeks of gestation. Methods: We collected data (2007–2010) of all women who developed GDM requiring insulin treatment and completed first-trimester combined screening program including the determination of serum PAPP-A and free β-human chorionic gonadotropin (β-hCG). A total of 288 women were included in this study. Each of the 72 women who developed GDM was matched with three unaffected controls. Results: Women with GDM were significantly older (34.2 ± 5.9 vs. 32.3 ± 5.5 years, P = 0.007) and delivered significantly earlier (38.40 ± 2.25 vs. 39.1 ± 2.2 gestational weeks, P = 0.01). Multiple regression analysis revealed, that PAPP-A and β-hCG were independently associated with each other (P = 0.04) but there was no association between GDM/no GDM and the first-trimester serum markers (P = 0.77). Conclusion: Our data suggest that women who are developing GDM needing insulin treatment do not have altered PAPP-A levels at 11–14 weeks.     

Is vaginal progesterone treatment associated with the development of gestational diabetes? A retrospective case–control study

Purpose

To determine the incidence of gestational diabetes mellitus (GDM) in pregnant women who received vaginal progesterone due to short cervical length or to prevent recurrent preterm birth.

Methods

In this retrospective study, we included 190 women with singleton pregnancies at risk for preterm birth who received vaginal natural progesterone (200 mg daily between gestational weeks 16?+?0 and 36?+?0) for a minimum of 4 weeks and delivered?>?28 weeks. The control group consisted of 242 age- and body mass index (BMI)-matched patients without progesterone administration. Data were acquired from a database containing prospectively collected information. Patients with pre-existing diabetes, and conception after in vitro fertilisation procedure were excluded.

Results

The incidence of GDM did not differ significantly between the progesterone-treated and the control group (14.7% vs. 16.9%, respectively; p?=?0.597). In a binary regression model, patients with higher pre-pregnancy BMI (OR 1.1; p?=?0.006), and those with a family history of diabetes had a higher risk for GDM development (OR 1.8; p?=?0.040), whereas vaginal progesterone treatment had no significant influence (p?=?0.580).

Conclusion

The use of vaginal progesterone for the prevention of recurrent preterm delivery and in women with a short cervix does not seem to be associated with an increased risk of GDM.

     

Isolated polyhydramnios in the third trimester: is a gestational diabetes evaluation of value?*

We evaluated implications of testing for gestational diabetes mellitus (GDM) in pregnancies complicated by third trimester isolated polyhydramnios with previous negative diabetes screening test. In this retrospective cohort study of 104 pregnant women with polyhydramnios between 2005 and 2013, all had normal first trimester fasting glucose and normal glucose challenge test (GCT?p?=?0.38) or fasting glucose values (82 vs. 86?mg/dL, p?=?0.29) between women in the polyhydramnios group with and without late GDM diagnosis. Moreover, no significant difference was found in relation to the mode of delivery or birth weight between the studied groups (3437?±?611 vs. 3331?±?515?g, p?=?0.63). Diagnosis of third trimester polyhydramnios was not associated with increased risk for GDM or neonatal complications.     

Is there a standard biological screening of gestational diabetes mellitus?

Universal screening for gestational diabetes mellitus (GDM) is contentious. There is insufficient evidence that universal screening for GDM substantially reduces perinatal complications such as cesarean section and Erb's palsy.However, risk assessment for GDM should be undertaken at the first prenatal visit and selective screening should be performed in high-risk women: diabetes mellitus in first-degree relatives, member of an ethnic group with a high prevalence of diabetes mellitus, body mass index > or 25 kg/m2, personal history of hyperglycemia or GDM, previous poor obstetric outcome. During the first trimester, a fasting glycemia over 1.05 g/l is associated with perinatal complications and should be treated. If fasting glycemia is below this level or unknown, or if glucosuria occurs, they should be re-tested between 24 and 28 weeks of gestation using a 75-g oral glucose load. The actual proposed glucose threshold values for GDM are, respectively, 1.05 and 1.55-1.60 g/l for fasting and 2 h.     

Do clinical prediction models improve concordance of treatment decisions in reproductive medicine?

OBJECTIVE: To assess whether the use of clinical prediction models improves concordance between gynaecologists with respect to treatment decisions in reproductive medicine. DESIGN: We constructed 16 vignettes of subfertile couples by varying fertility history, postcoital test, sperm motility, follicle-stimulating hormone level and Chlamydia antibody titre. SETTING: Thirty-five gynaecologists estimated three probabilities, i.e. the 1-year probability of spontaneous pregnancy, the pregnancy chance after intrauterine insemination (IUI) and the pregnancy chance after in vitro fertilisation (IVF). Subsequently they proposed therapeutic regimens for these 16 fictional couples, i.e. expectant management, IUI or IVF. Three months later, the participant gynaecologists again had to propose therapeutic regimes for the same 16 fictional cases but this time accompanied by pregnancy chances obtained from prediction models: predictions on spontaneous pregnancy, IUI and IVF. POPULATION: Thirty-five gynaecologists working in academic and nonacademic hospitals in the Netherlands. METHODS: Setting section. Main outcome measures The concordance between gynaecologists of probability estimates, expressed as interclass correlation coefficient (ICC) and the concordance between gynaecologists of treatment decisions, analysed by calculating Cohen's kappa (kappa). RESULTS: The gynaecologists differed widely in estimating pregnancy chances (ICC: 0.34). Furthermore, there was a huge variation in the proposed therapeutic regimens (kappa: 0.21). The treatment decisions made by gynaecologists were consistent with the ranking of their probability estimates. When prediction models were used, the concordance (kappa) for treatment decisions increased from 0.21 to 0.38. The number of gynaecologists counselling for expectant management increased from 39 to 51%, whereas counselling for IVF dropped from 23 to 14%. CONCLUSION: Gynaecologists differed widely in their estimation of prognosis in 16 fictional cases of subfertile couples. Their therapeutic regimens showed likewise huge variation. After confrontation with prediction models in the same 16 fictional cases, the proposed therapeutic regimens showed only slightly better concordance. Therefore a simple introduction of validated prediction models is insufficient to introduce concordant management between doctors.     

Serum fructosamine and fructosamine – albumin ratio as screening tests for gestational diabetes mellitus

To evaluate the role of fructosamine/albumin ratio as an alternative screening parameter for gestational diabetes mellitus (GDM), serum fructosamine, albumin, protein, fructosamine/albumin ratio, and oral glucose tolerance were measured in 56 non-pregnant control healthy subjects, and in 96 pregnant women who screened positive after a 50 g glucose challenge-test. Oral glucose tolerance test (OGTT) identified 12 of 96 pregnant women as having GDM. Fructosamine concentration of 1.98±0.32 mmol/L (mean±SD) and fructosamine/albumin ratio of 47±10 μmol/g (mean±SD) has been obtained in nonpregnant control subjects. During the second trimester a lower fructosamine level (1.84±0.29 mmol/L, p<0.05) and a higher fructosamine/albumin ratio (62±15 μmol/g, p<0.001) occurs in pregnant women, when compared to non-pregnant healthy control subjects, most likely due to the low serum albumin concentration (30±6 g/L). The serum fructosamine levels and fructosmine/albumin ratio were only slightly higher in the pregnant women with GDM than in normal pregnant women (2.05±0.47 mmol/L versus 1.84±0.29 mmol/L, 67±16 μmol/g versus 62±15 μmol/g, respectively) but the differences were not statistically significant. The fructosamine and fructosamine/albumin ratio values for normal and GDM groups overlapped considerably. Sensitivity, specificity, positive predictive and negative predictive values for fructosamine were 41.7%, 85.7%, 29.4% and 91%, and for fructosamine/albumin ratio 25%, 79.8%, 15% and 88% respectively. This suggests that both fructosamine and fructosamine/albumin ratio have low sensitivity as predictors of GDM and can therefore not be used as screening tests. Received: 29 June 1998 / Accepted: 20 August 1998     

Refusal of treatment in obstetrics – A maternal–fetal conflict

Objective.?Clinical studies about the necessity of standard obstetric interventions raise questions, making refusal by pregnant women of treatment a legitimate choice. The present study was aimed at characterising patients refusing medical treatment during pregnancy and delivery, and to examine whether refusal of treatment in obstetrics is associated with adverse perinatal outcome.

Methods.?A population-based study, comparing patients who refused (1898) and did not refuse (164,064) medical intervention during pregnancy and delivery, was conducted. Deliveries occurred between the years 1988 and 2002 in a tertiary medical centre.

Results.?Patients refusing medical intervention tended to be older (30.5 ± 5.0 vs. 28.4 ± 5.9, p < 0.001) and of higher parity (above parity 5: 52.5% vs. 32.4%; parity 1: 10.2% vs. 20.0%; p < 0.001) than the controls. Parturients refusing medical treatment experienced significantly higher rates of adverse perinatal outcome including low Apgar scores (less than 7, in 1 and 5 min: 12.4% vs. 4.4%, p < 0.001 and 1.9% vs. 0.6%, p < 0.001, respectively). Moreover, higher rates of perinatal mortality in general and intra-partum death, in particular, were documented among women refusing medical treatment (3.3% vs. 1.5%, p < 0.001; 0.8% vs. 0.1%, p < 0.001). When using a multiple logistic regression model of risk factors for perinatal mortality, refuse of treatment was an independent risk factor for perinatal mortality (OR = 1.5; 95% CI = 1.1–2.0; p = 0.010).

Conclusion.?Patients refusing a medically indicated intervention have higher rates of pregnancy- and labour- related complications. Refusal of treatment is an independent risk factor for perinatal mortality.     

Does the presence of polycystic ovary syndrome increase the risk of obstetrical complications in women with gestational diabetes?

Objective.?To determine whether women with both polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) have an increased risk of obstetric complications compared with women with GDM alone.

Methods.?A retrospective cohort study of maternal/fetal outcomes in women with GDM and PCOS was compared with women with GDM alone. Outcomes were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Logistic regression models allowed for the calculation of odds ratios and 95% confidence intervals (CIs) for each outcome, adjusted for confounding.

Results.?One hundred seventy one women were included in the study. Significantly more women with both GDM and PCOS had pregnancy-induced hypertension/preeclampsia (15.9% vs. 3.9%, p?=?0.019, OR?=?4.62, 95% CI?=?1.38–15.41). Multiple logistic regression revealed that this increase persisted after controlling for body mass index (p?=?0.028, OR?=?4.43, 95% CI?=?1.17–16.72) and parity (p?=?0.050, OR?=?3.45, 95% CI?=?1.00–11.92). Women with GDM and PCOS tended to have more preterm deliveries (25.0% vs. 11.8%, p?=?0.063). More infants of women with GDM and PCOS required phototherapy treatment for hyperbilirubinemia (25.0% vs. 7.9%, p?=?0.0066, OR?=?3.90, 95% CI?=?1.52–9.98). Logistic regression revealed that this association persisted after controlling for preterm delivery (OR?=?3.18, 95% CI?=?1.14–8.82, p?=?0.026).

Conclusions.?Mothers with both disorders should be monitored more carefully and counseled regarding their increased risk of both maternal and fetal complications.     

Thiol/disulfide homeostasis in predicting adverse perinatal outcomes at 24–28 weeks of pregnancy in gestational diabetes

Objective: The main aim of this study was to investigate thiol/disulfide homeostasis at 24–28 weeks of pregnancy and to evaluate whether it is predictive for adverse perinatal outcomes or not in gestational diabetes mellitus (GDM).

Methods: A total of 110 pregnant women at 24–28 weeks of pregnancy (74 GDM patients and 36 age- and BMI-matched healthy pregnant women) were enrolled in this prospective case–control study. Thiol/disulfide homeostasis was evaluated with a novel spectrophotometric method to determine if there is an association with adverse perinatal outcomes in GDM, by using logistic regression analysis.

Results: GDM patients, with decreased native thiol levels at 24–28 weeks (OR: 4.890, 95% CI: 1.355–5.764, p?=?0.015) and with higher pre-pregnancy BMI (OR: 1.280, 95% CI: 1.072–1.528, p?=?0.006), were found to be at increased risk of adverse perinatal outcomes in GDM. There were no statistically significant differences in thiol/disulfide homeostasis between diet- and insulin-treated GDM subgroups. Additionally, 1-h and 2-h glucose levels on 100?g OGTT were found to be predictive for the insulin need in achieving good glycemic control in GDM (OR: 1.022, 95% CI: 1.005–1.038, p?=?0.010 and OR: 1.019, 95% CI: 1.004–1.035, p?=?0.015).

Conclusions: GDM patients, with decreased native thiol levels at 24–28 weeks of pregnancy and with higher pre-pregnancy BMI, have an increased risk of possible adverse perinatal outcomes. Also, increased 1-h and 2-h glucose levels on 100?g OGTT can predict the need for insulin treatment for GDM.