The Prognosis of Glutamic Acid Decarboxylase Antibodies in Women With Hyperglycemia in Pregnancy.

CONTEXT: We recently reported that the presence of glutamic acid decarboxylase antibodies (GADA) was not associated with large-for-gestational-age infants in women with hyperglycemia in pregnancy (HIP). OBJECTIVE: We explored the association between the presence of GADA and other HIP-related adverse pregnancy outcomes. METHODS: This observational prospective study, conducted at a university hospital in a suburb of Paris, France, included 1182 consecutive women with HIP measured for GADA at HIP care initiation between 2012 and 2017. Post hoc analyses for outcomes included gestational weight gain, insulin therapy, cesarean delivery, hypertensive disorders, small-for-gestational-age infant, prematurity, and neonatal hypoglycemia. RESULTS: Of the 1182 women studied, 87 (7.4%) had positive (≥ 1 IU/mL) GADA. Although socioeconomic, clinical, and biological characteristics were similar across women in the positive and negative GADA groups, higher fasting plasma glucose values during early HIP screening were observed in the former (5.5 ± 1.5 vs 5.2 ± 0.7 mmol/L respectively, P < .001). At HIP care initiation, fructosamine levels were higher in women with positive GADA (208 ± 23 vs 200 ± 18 µmol/L; P < .05). In the homeostatic model assessment, insulin resistance (HOMA-IR) and beta secretion (HOMA-B) rates were similar in both groups. Gestational weight gain and the rates of all adverse outcomes were similar in both groups except for cesarean delivery (18.4 and 27.3% for positive and negative GADA, respectively; adjusted odds ratio 0.49 [95% CI, 0.26-0.92], P = .026). CONCLUSION: Universal measurement of GADA in women with HIP highlighted that 7.4% had positive GADA. No association was observed between GADA and HIP-related adverse pregnancy outcomes, except a lower risk of cesarean delivery.

Glycemic status during pregnancy according to fasting and post-load glucose values: The association with adverse pregnancy outcomes. An observational study.

AIM: Prognosis of treated hyperglycemia in pregnancy (HIP) may differ according to whether diagnosis following an oral glucose tolerance test (OGTT) is based on high fasting and/or high post-load glucose values. METHODS: From a multiethnic prospective study, we included 8,339 women screened for HIP after 22 weeks of gestation. We evaluated the risk of large-for-gestational-age (LGA) infant (primary endpoint) and other adverse pregnancy outcomes according to HIP status in four groups defined as follows: no HIP (n = 6,832, reference); isolated fasting HIP (n = 465), isolated post-load HIP (n = 646), and fasting and post-load HIP (n = 396). RESULTS: After adjusting for age, body mass index, ethnicity, smoking during pregnancy and parity, compared with no HIP, the adjusted odds ratios [95% confidence interval] for LGA infant were higher in the isolated fasting HIP (1.47 [1.11-1.96]) and fasting and post-load HIP (1.65 [1.23-2.21]) groups, but not in the isolated post-load HIP (1.13 [0.86-1.48]) group. The adjusted odds ratios for preterm delivery and neonatal intensive care unit were higher in the post-load HIP group (1.44 [1.03-2.03] and 1.28 [1.04-1.57], respectively), the fasting and post-load HIP group (1.81 [1.23-2.68] and 1.42 [1.10-1.81], respectively) but not in the isolated fasting HIP group (1.34 [0.90-2.00] and 1.20 [0.94-1.52], respectively). CONCLUSION: Despite glucose-lowering care and adjustment for confounders, compared with no HIP, fasting HIP was associated with a higher rate of LGA infant, whereas post-load HIP was associated with higher preterm delivery and neonatal intensive care unit admission rates.

Is there a residual risk of large-for-gestational-age infant related to gestational diabetes mellitus when it is treated?

OBJECTIVE: The hyperglycaemia and adverse pregnancy outcomes (HAPO) study, where hyperglycaemia was untreated, showed a continuous association between large-for-gestational-age (LGA) infant and seven increasing categories of fasting plasma glucose (PG), 1-hour and 2-hour PG values after a 75 g oral glucose tolerance test at 24-32 gestational weeks. We evaluated whether the excess risk persisted in the 6th and 7th glucose categories - corresponding to women treated for gestational diabetes mellitus (GDM). PATIENTS AND METHODS: We included 7,190 women meeting the HAPO criteria, of whom 655 (9.2%) were treated for GDM (dietary education in all; insulin therapy in 150 (20.3%)). We evaluated the adjusted odds ratio (aOR) for each glucose category (reference 1st category) for LGA infant. RESULTS: The aOR for LGA linearly increased from the 1st to 5th categories of fasting, 1-hour and 2-hour PG. Specifically, the aORs for the 5th category were 2.20 (95% confidence interval 1.41-3.44), 2.25 (1.11-4.59), and 2.51 (1.63-3.85), respectively. The aORs for the 6th category were globally stable at 2.52 (1.46-4.36), 2.87 (1.48-5.54), and 2.47 (1.46-4.16), respectively. The same was true for the 7th category: 1.41 (0.56-3.55), 2.84 (1.03-7.86), and 3.53 (1.77-7.06), respectively. CONCLUSION: We confirmed the association between increasing PG category and LGA infant in women without GDM. We did not observe a residual risk of LGA infant in women treated for GDM in our hospital, irrespective of elevated fasting, 1-hour, or 2-hour PG diagnosis. The risk of LGA infant was globally similar to that in women with high normal glucose values.

Metabolic characteristics and adverse pregnancy outcomes for women with hyperglycaemia in pregnancy as a function of insulin resistance.

AIM: Recent studies have shown that women with hyperglycaemia in pregnancy and insulin resistance have a greater risk of adverse pregnancy outcomes than women with normoglycaemic pregnancies. This study aimed to determine adverse pregnancy outcomes of women with hyperglycaemia in pregnancy only as a function of insulin resistance. METHODS: From a prospective cohort study, we included 1,423 women with hyperglycaemia in pregnancy whose insulin resistance was evaluated using homoeostatic model assessment for insulin resistance (HOMA-IR) when care was first provided for this condition. We compared the adverse pregnancy outcomes for different tertiles of HOMA-IR (intertertile range 1.9 and 3.3). RESULTS: Increasing HOMA-IR tertiles were positively associated with the rate of insulin therapy (tertile 1, 2 and 3: 32.7, 47.0 and 58.7%, P < 0.0001), caesarean section (23.7, 26.0 and 32.2%, respectively, P < 0.01), gestational hypertension (1.3, 2.8 and 5.4% respectively, P < 0.01), preeclampsia (1.5, 2.8 and 4.5% respectively, P < 0.05), large-for-gestational-age infant (13.3, 10.4 and 17.6% respectively, P < 0.05), and neonatal hypoglycaemia (0.8, 1.5 and 3.2% respectively, P < 0.05). Women in the 3rd HOMA-IR tertile were more likely to have insulin therapy (odds ratio 2.09 (95% interval confidence 1.61-2.71)), hypertensive disorders (2.26 (1.42-3.36)), and large-for-gestational-age infant (1.42 (1.01-1.99)) than those in the 1st and 2nd tertiles combined in multivariable logistic regression analyses adjusted for gestational age at HOMA-IR measurement, glycaemic status, age, body mass index, family history of diabetes, parity and ethnicity. CONCLUSION: Despite suitable care and increased rates of insulin therapy during pregnancy, higher insulin resistance in women with hyperglycaemia in pregnancy was associated with a greater risk of adverse pregnancy outcomes.

Prognosis Associated with Sub-Types of Hyperglycaemia in Pregnancy.

We aimed to compare pregnancy outcomes in 4665 women according to the following types of hyperglycaemia in pregnancy sub-types: (i) normoglycaemia, (ii) gestational diabetes mellitus (GDM), (iii) diabetes in pregnancy (DIP), (iv) early-diagnosed (i.e., <22 weeks of gestation) GDM (eGDM), and (v) early-diagnosed DIP (eDIP). The prevalence of normoglycaemia, eGDM, eDIP, GDM, and DIP was 76.4%, 10.8%, 0.6%, 11.7%, and 0.6%, respectively. With regard to pregnancy outcomes, gestational weight gain (11.5 ± 5.5, 9.0 ± 5.4, 8.3 ± 4.7, 10.4 ± 5.3, and 10.1 ± 5.0 kg, p < 0.0001) and insulin requirement (none, 46.0%, 88.5%, 25.5%, and 51.7%; p < 0.001) differed according to the glycaemic sub-types. eGDM and eDIP were associated with higher rates of infant malformation. After adjustment for confounders, with normoglycaemia as the reference, only GDM was associated with large-for-gestational-age infant (odds ratio 1.34 (95% interval confidence 1.01-1.78) and only DIP was associated with hypertensive disorders (OR 3.48 (1.26-9.57)). To conclude, early-diagnosed hyperglycaemia was associated with an increased risk of malformation, suggesting that it was sometimes present at conception. Women with GDM, but not those with eGDM, had an increased risk of having a large-for-gestational-age infant, possibly because those with eGDM were treated early and therefore had less gestational weight gain. Women with DIP might benefit from specific surveillance for hypertensive disorders.

Limiting the Use of Oral Glucose Tolerance Tests to Screen for Hyperglycemia in Pregnancy during Pandemics.

We aimed to evaluate each proposal of Australian-New Zealand Societies to limit the number of oral glucose tolerance tests (OGTTs) to diagnose hyperglycemia in pregnancy (HIP) during the coronavirus disease 2019 (COVID-19) pandemic. At our university hospital (2012-2016), we retrospectively applied in 4245 women who had OGTT between 22 and 30 weeks of gestation (reference standard: WHO criteria) the proposals in which OGTT is performed only in high-risk women; in all (Option 1) or high-risk (Option 1-Sel) women with fasting plasma glucose (FPG) 4.7-5.0 mmol/L; in all (Option 2) or high-risk (Option 2-Sel) women without history of HIP and with FPG 4.7-5.0 mmol/L. We also tested FPG measurement alone in all high-risk women. Measuring FPG alone had a sensitivity of 49% (95% confidence interval 45-54) applying universal screening. Option 2 appeared to have the best balance considering the needed OGTT (17.3%), sensitivity (72% (67-76)) and rates of a composite outcome (true negative cases: 10.6%, false positive cases: 24.4%; true positive cases: 19.5%; false negative cases: 10.2%). Consideration of a history of HIP and measuring first FPG can avoid more than 80% of OGTTs and identify women with the highest risk of adverse HIP-related events.

Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies.

Polycystic ovary syndrome (PCOS) is marked in 30 to 40% by insulin resistance and hyperandrogenism. Myo-inositol (MI) increases insulin sensitivity, decreases hyperandrogenism and improves the menstrual cycle. Its effect during assisted reproductive technologies (ART) has been studied by many authors. We conducted a review of the literature on the impact of MI administration in PCOS women in assisted reproductive technologies. Myo-inositol is effective in normalizing ovarian function, improving oocyte and embryo quality in PCOS, however further evaluations by large multicentre randomized controlled trials are needed to assess the clinical pregnancy and live birth rates in ART.

COVID-19 pandemic: Can fasting plasma glucose and HbA1c replace the oral glucose tolerance test to screen for hyperglycaemia in pregnancy?

AIMS: To evaluate proposals considering HbA1c and fasting plasma glucose (FPG) measurement as a substitute for oral glucose tolerance test (OGTT) to diagnose hyperglycaemia in pregnancy (HIP) during COVID-19 pandemic. METHODS: Of the 7,334 women who underwent the OGTT between 22 and 30 weeks gestation, 966 had HIP (WHO diagnostic criteria, reference standard). The 467 women who had an available HbA1c were used for analysis. French-speaking Society of Diabetes (SFD) proposal to diagnose HIP during COVID-19 pandemic was retrospectively applied: HbA1c ≥5.7% (39 mmol/mol) and/or FPG level ≥5.1 mmol/l. SFD proposal sensitivity for HIP diagnosis and the occurrence of HIP-related events (preeclampsia, large for gestational age infant, shoulder dystocia or neonatal hypoglycaemia) in women with false negative (FN) and true positive (TP) HIP-diagnoses were evaluated. RESULTS: The sensitivity was 57% [95% confidence interval 52-62]. FN women had globally lower plasma glucose levels during OGTT, lower HbA1c and body mass index than those TP. The percentage of HIP-related events was similar in FN (who were cared) and TP cases, respectively 19.5 and 16.9% (p = 0.48). We observed similar results when women at high risk for HIP only were considered. CONCLUSION: The SFD proposal has a poor sensitivity to detect HIP. Furthermore, it fails to have any advantages in predicting adverse outcomes.