Normal glucose tolerant women with low glycemia during the oral glucose tolerance test have a higher risk to deliver a low birth weight infant.

Background: Data are limited on pregnancy outcomes of normal glucose tolerant (NGT) women with a low glycemic value measured during the 75g oral glucose tolerance test (OGTT). Our aim was to evaluate maternal characteristics and pregnancy outcomes of NGT women with low glycemia measured at fasting, 1-hour or 2-hour OGTT. Methods: The Belgian Diabetes in Pregnancy-N study was a multicentric prospective cohort study with 1841 pregnant women receiving an OGTT to screen for gestational diabetes (GDM). We compared the characteristics and pregnancy outcomes in NGT women according to different groups [(<3.9mmol/L), (3.9-4.2mmol/L), (4.25-4.4mmol/L) and (>4.4mmol/L)] of lowest glycemia measured during the OGTT. Pregnancy outcomes were adjusted for confounding factors such as body mass index (BMI) and gestational weight gain. Results: Of all NGT women, 10.7% (172) had low glycemia (<3.9 mmol/L) during the OGTT. Women in the lowest glycemic group (<3.9mmol/L) during the OGTT had compared to women in highest glycemic group (>4.4mmol/L, 29.9%, n=482), a better metabolic profile with a lower BMI, less insulin resistance and better beta-cell function. However, women in the lowest glycemic group had more often inadequate gestational weight gain [51.1% (67) vs. 29.5% (123); p<0.001]. Compared to the highest glycemia group, women in the lowest group had more often a birth weight <2.5Kg [adjusted OR 3.41, 95% CI (1.17-9.92); p=0.025]. Conclusion: Women with a glycemic value <3.9 mmol/L during the OGTT have a higher risk for a neonate with birth weight < 2.5Kg, which remained significant after adjustment for BMI and gestational weight gain.

Low Gestational Weight Gain in Women With Gestational Diabetes Is Safe With Better Metabolic Profile Postpartum.

CONTEXT: More data are needed on the potential benefits and risks of gestational weight gain (GWG) less than recommended and excessive GWG in women with gestational diabetes (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy. OBJECTIVE: This work aimed to evaluate association of gestational weight gain (GWG) as low, within, or above (excessive) according to Institute of Medicine (IOM) guidelines, with pregnancy outcomes in women with gestational diabetes (GDM) and normal glucose tolerance (NGT). METHODS: This prospective cohort study included 7 Belgian hospitals and 1843 women receiving universal GDM screening with a 75-g oral glucose tolerance test. Pregnancy outcomes and postpartum characteristics were the main outcome measures. RESULTS: Women with GDM and low GWG (n = 97, 52.4%) had similar rates of small-for-gestational age infants and preterm delivery, were less often overweight or obese postpartum (35.7% [30] vs 56.5% [26]; P < .022) and less often had postpartum weight retention (PPWR) (48.8% [41] vs 87.9% [40]; P < .001) compared to GWG within range (n = 58, 31.3%). GDM with excessive GWG (n = 30, 16.2%) more often had neonatal hypoglycemia (30.8% (8) vs 5.9% [3], aOR 7.15; 95% CI, 1.52-33.63; P = .013) compared to GWG within range. NGT with excessive GWG (28.3% [383]) more often had instrumental delivery (15.9% [61] vs 11.9% [64], aOR 1.53; 95% CI, 1.03-2.27; P = .035) and more large-for-gestational age infants (19.3% [74] vs 10.4% [56], aOR 1.67; 95% CI, 1.13-2.47; P = .012) compared to GWG within range. CONCLUSION: GWG below IOM guidelines occurred frequently in GDM women, without increased risk for adverse pregnancy outcomes and with better metabolic profile postpartum. Excessive GWG was associated with increased risk for neonatal hypoglycemia and worse metabolic profile postpartum in women with GDM, and with higher rates of LGA and instrumental delivery in NGT women.

Higher Thyroid fT3-to-fT4 Ratio Is Associated with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

Aim: To determine the association between thyroid function and the risk of developing gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Methods: This case−control study was a sub-analysis of the BEDIP-N study, in which 199 GDM women were matched for age and body mass index with 398 controls. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and thyroid peroxidase (TPO) antibodies were measured at 6−14 weeks and 26−28 weeks during pregnancy. TSH and fT4 were also measured in early postpartum in GDM women. Results: The fT3-to-fT4 ratio at 26−28 weeks was positively associated with GDM risk with an adjusted odds ratio (aOR for smoking, education, parity, ethnicity, gestational weight gain, and (family) history of diabetes or GDM) of 2.12 (95% CI 1.07; 4.23), comparing the highest with the lowest tertile. Higher fT3 levels and a higher fT3-to-fT4 ratio were associated with a less favorable metabolic profile with higher BMI and more insulin resistance during pregnancy and postpartum. Women in the upper fT3 tertile and the upper fT3-to-fT4 ratio had a higher rate of preeclampsia [4.6% (10) vs. 1.0% (2), p = 0.040, and 4.4% (9) vs. 0.5% (1), p = 0.020], gestational hypertension [8.3% (18) vs. 3.1% (6), p = 0.034 and 8.9% (18) vs. 2.0% (4), p = 0.003], and caesarean sections [29.4% (63) vs. 16.1% (31), p = 0.002 and 32.2% (65) vs. 12.7% (25), p < 0.001]. Conclusion: A higher fT3-to-fT4 ratio late into pregnancy was associated with GDM, adverse pregnancy outcomes, and an adverse metabolic profile in early postpartum.

Type 1 diabetes-related autoimmune antibodies in women with gestational diabetes mellitus and the long-term risk for glucose intolerance.

Aims: To characterize women with gestational diabetes mellitus (GDM) positive for type 1 diabetes-related autoimmune antibodies (T1D-related autoantibodies) in pregnancy and to evaluate their risk for long-term glucose intolerance. Methods: In a multi-centric prospective cohort study with 1843 women receiving universal screening for GDM with a 75 g oral glucose tolerance test (OGTT), autoantibodies were measured in women with GDM: insulin autoantibodies (IAA), islet cell antibodies (ICA), insulinoma-associated protein-2 antibodies (IA-2A) and glutamic acid decarboxylase antibodies (GADA). Long-term follow-up ( ± 4.6 years after delivery) with a 75 g OGTT and re-measurement of autoantibodies was done in women with a history of GDM and autoantibody positivity in pregnancy. Results: Of all women with GDM (231), 80.5% (186) received autoantibody measurement at a mean of 26.2 weeks in pregnancy, of which 8.1% (15) had one positive antibody (seven with IAA, two with ICA, four with IA-2A and two with GADA). Characteristics in pregnancy were similar but compared to women without autoantibodies, women with autoantibodies had more often gestational hypertension [33.3% (5) vs. 1.7% (3), p<0.001] and more often neonatal hypoglycemia [40.0% (6) vs. 12.5% (19), p=0.012]. Among 14 of the 15 autoantibody positive women with an early postpartum OGTT, two had impaired fasting glucose (IFG). Of the 12 women with long-term follow-up data, four tested again positive for T1D-related autoantibodies (three positive for IA-2A and one positive for ICA and IAA). Five women were glucose intolerant at the long-term follow-up of which two had IA-2A (one had IFG and one had T1D) and three without autoantibodies. There were no significant differences in long-term characteristics between women with and without autoantibodies postpartum. Conclusions: Systematic screening for T1D-related autoantibodies in GDM does not seem warranted since the low positivity rate for autoantibodies in pregnancy and postpartum. At 4.6 years postpartum, five out of 12 women were glucose intolerant but only two still had autoantibodies. In women with clinically significant increased autoantibody levels during pregnancy, postpartum autoantibody re-measurement seems useful since the high risk for further increase of autoantibody levels.

TPO antibody status prior to first radioactive iodine therapy as a predictive parameter for hypothyroidism in Graves' disease.

Objective: We investigated whether a positive thyroid peroxidase antibody (TPO Ab) status before radioactive iodine (RAI) therapy in patients with Graves' hyperthyroidism is a predictive factor for developing hypothyroidism post RAI. Methods: We performed a retrospective study of patients with Graves' hyperthyroidism with known TPO Ab status, receiving the first administration of RAI. Patients from four thyroid outpatient centres in Belgium receiving their first RAI therapy between the years 2011 and 2019 were studied. Clinical, laboratory, imaging, and treatment data were recorded from medical charts. Hypothyroidism and cure (defined as combined hypo- and euthyroidism) were evaluated in period 1 (≥2 and ≤9 months, closest to 6 months post RAI) and period 2 (>9 months and ≤24 months post RAI, closest to 12 months post RAI). Results: A total of 152 patients were included of which 105 (69%) were TPO Ab-positive. Compared to TPO Ab-negative patients, TPO Ab-positive patients were younger, had a larger thyroid gland, and had more previous episodes of hyperthyroidism. In period 1, 89% of the TPO Ab-positive group developed hypothyroidism and 72% in the TPO Ab-negative group (P = 0.007). In period 2, the observation was similar: 88% vs 72% (P = 0.019). In the multivariate logistic regression analysis, a positive TPO Ab status was associated with hypothyroidism in period 2 (adjusted OR: 4.78; 95% CI: 1.27-20.18; P = 0.024). In period 1, the aOR was 4.16 (95% CI: 1.0-18.83; P = 0.052). Conclusion: A positive TPO Ab status in patients with Graves' hyperthyroidism receiving the first administration of RAI is associated with a higher risk of early hypothyroidism.

Neoplasia in Turner syndrome: a retrospective cohort study in a tertiary referral centre in Belgium.

OBJECTIVES: Patients with Turner syndrome (TS), the most common sex chromosome abnormality in women, can suffer from a variety of well-researched reproductive, cardiovascular, metabolic, and autoimmune comorbidities. Few studies investigate the neoplasia risk. We assessed the general neoplasia risk in TS women, and more specifically, the gonadoblastoma/dysgerminoma risk in the subgroup with Y chromosome mosaicism, and evaluated potential risk factors for neoplasia development, such as karyotype, metabolic and autoimmune comorbidity, and treatment with growth hormone and/or estrogen replacement. DESIGN: 10-year retrospective cohort study in a tertiary referral centre in Belgium. RESULTS: 105 TS women were included (median age 29; range 2-69). Six malignant tumours were detected in 5 (4.8%) patients (SIR = 0.6, 95% CI 0.2-1.0). In addition, 2 benign meningiomas were observed, resulting in 3 (2.9%) tumours of the central nervous system (CNS; SIR = 19.9, 95% CI 4.0-35.8). No breast cancer was noted. Benign neoplasms occurred in 22 women (21.0%), with skin lesions being the most frequent. All patients with Y chromosome mosaicism (n = 9; 8.6%) underwent prophylactic gonadectomy, but gonadoblastoma/dysgerminoma was not detected. A weak association was found between any tumour type and autoimmune comorbidity (r = 0.24; p = 0.02). CONCLUSION: The overall malignancy risk was not increased, but a different pattern of occurrence is apparent, with an increased risk of CNS and skin tumours and a decreased breast cancer risk. Gonadoblastoma/dysgerminoma was not reported. There is a need for centralised multidisciplinary care and prospective research to unravel and predict the neoplasia risk.

Fasting plasma glucose level to guide the need for an OGTT to screen for gestational diabetes mellitus.

AIMS: To determine the fasting plasma glucose (FPG) level at which an oral glucose tolerance test (OGTT) could be avoided to screen for gestational diabetes (GDM) and to evaluate the characteristics of women across this FPG threshold. METHODS: A multi-centric prospective cohort study with 1843 women receiving universal screening for GDM with a 75 g OGTT. RESULTS: In the total population, GDM prevalence was 12.5% (231). A FPG < 78 mg/dL was the cut-off with best trade-off to limit the number of missed GDM cases [44 (19.0%)] with a negative predictive value of 97.3% (95% CI 96.5-98.0) for GDM, while avoiding 52.2% OGTTs. Compared to GDM with FPG ≥ 78 mg/dL [187 (81.0%)], GDM women with FPG < 78 mg/dL had a significantly lower BMI (27.1 ± 4.5 vs. 29.6 ± 5.2 kg/m2, p = 0.003), less insulin resistance [Matsuda: 0.4 (0.4-0.7) vs. 0.3 (0.2-0.5), p < 0.001] and better ß-cell function [ISSI-2: 0.13 (0.08-0.25) vs. 0.09 (0.04-0.15), p = 0.004]. Compared to NGT women (1612) with FPG ≥ 78 mg/dL [846 (52.5%)], NGT with FPG < 78 mg/dL [766 (47.5%)] had a significantly lower BMI (26.0 ± 3.9 vs. 27.8 ± 4.7 kg/m2, p < 0.001), less insulin resistance [Matsuda: 0.7 (0.5-0.9) vs. 0.5 (0.4-0.7), p < 0.001], better ß-cell function [ISSI-2: 0.17 (0.10-0.30) vs. 0.12 (0.07-0.21), p < 0.001], and less often large-for-gestational age infants [9.2 (70) vs. 16.2% (136), p < 0.001]. CONCLUSIONS: FPG < 78 mg/dL can be used to limit the number of OGTTs when screening for GDM. Women with FPG < 78 mg/dL had a better metabolic profile and in NGT women also less fetal overgrowth.

Liraglutide for Weight Management in the Real World: Significant Weight Loss Even if the Maximal Daily Dose Is Not Achieved.

INTRODUCTION: Obesity is a global health challenge, and pharmacologic options are emerging. Once daily subcutaneous administration of 3 mg liraglutide, a glucagon like peptide-1 analogue, has been shown to induce weight loss in clinical trials, but real-world effectiveness data are scarce. METHODS: It is a single-centre retrospective cohort study of patients who were prescribed liraglutide on top of lifestyle adaptations after multidisciplinary evaluation. In Belgium, liraglutide is only indicated for weight management if the BMI is >30 kg/m2 or ≥27 kg/m2 with comorbidities such as dysglycaemia, dyslipidaemia, hypertension, or obstructive sleep apnoea. No indication is covered by the compulsory health care insurance. Liraglutide was started at 0.6 mg/day and uptitrated weekly until 3 mg/day or the maximum tolerated dose. Treatment status and body weight were evaluated at the 4-month routine visit. RESULTS: Between June 2016 and January 2020, liraglutide was prescribed to 115 patients (77% female), with a median age of 47 (IQR 37.7-54.0) years, a median body weight of 98.4 (IQR 90.0-112.2) kg, a BMI of 34.8 (IQR 32.2-37.4) kg/m2, and an HbA1c level of 5.6%. Five (4%) patients did not actually initiate treatment, 9 (8%) stopped treatment, and 8 (7%) were lost to follow-up. At the 4-month visit, the median body weight had decreased significantly by 9.2% to 90.8 (IQR 82.0-103.5) kg (p < 0.001). Patients using 3.0 mg/day (n = 60) had lost 8.0 (IQR 5.8-10.4) kg. The weight loss was similar (p = 0.9622) in patients that used a lower daily dose because of intolerance: 7.4 (IQR 6.2-9.6) kg for 1.2 mg (n = 3), 7.8 (IQR 4.1-7.8) kg for 1.8 mg (n = 16), and 9.0 (IQR 4.8-10.7) kg for 2.4 mg/day (n = 14). Weight loss was minimal if liraglutide treatment was not started or stopped prematurely (median 3.0 [IQR 0.3-4.8] kg, p < 0.001, vs. on treatment). Further analysis showed an additional weight reduction of 1.8 kg in the patients that had started metformin <3 months before the start of liraglutide (p < 0.001). The main reasons for liraglutide discontinuation were gastrointestinal complaints (n = 5/9) and drug cost (n = 2/9). CONCLUSION: In this selected group of patients, the majority complied with liraglutide treatment over the initial 4-month period and achieved a significant weight loss, irrespective of the maximally tolerated maintenance dose. Addition of metformin induced a small but significant additional weight loss.

Preference of Women for Gestational Diabetes Screening Method According to Tolerance of Tests and Population Characteristics.

Aims: To determine the preferred method of screening for gestational diabetes mellitus (GDM). Methods: 1804 women from a prospective study (NCT02036619) received a glucose challenge test (GCT) and 75g oral glucose tolerance test (OGTT) between 24-28 weeks. Tolerance of screening tests and preference for screening strategy (two-step screening strategy with GCT compared to one-step screening strategy with OGTT) were evaluated by a self-designed questionnaire at the time of the GCT and OGTT. Results: Compared to women who preferred one-step screening [26.2% (472)], women who preferred two-step screening [46.3% (834)] were less often from a minor ethnic background [6.0% (50) vs. 10.7% (50), p=0.003], had less often a previous history of GDM [7.3% (29) vs. 13.8% (32), p=0.008], were less often overweight or obese [respectively 23.1% (50) vs. 24.8% (116), p<0.001 and 7.9% (66) vs. 18.2% (85), p<0.001], were less insulin resistant in early pregnancy (HOMA-IR 8.9 (6.4-12.3) vs. 9.9 (7.2-14.2), p<0.001], and pregnancy outcomes were similar except for fewer labor inductions and emergency cesarean sections [respectively 26.6% (198) vs. 32.5% (137), p=0.031 and 8.2% (68) vs. 13.0% (61), p=0.005]. Women who preferred two-step screening had more often complaints of the OGTT compared to women who preferred one-step screening [50.4% (420) vs. 40.3% (190), p<0.001]. Conclusions: A two-step GDM screening involving a GCT and subsequent OGTT is the preferred GDM screening strategy. Women with a more adverse metabolic profile preferred one-step screening with OGTT while women preferring two-step screening had a better metabolic profile and more discomfort of the OGTT. The preference for the GDM screening method is in line with the recommended Flemish modified two-step screening method, in which women at higher risk for GDM are recommended a one-step screening strategy with an OGTT, while women without these risk factors, are offered a two-step screening strategy with GCT. Clinical Trial Registration: NCT02036619 https://clinicaltrials.gov/ct2/show/NCT02036619.

Diabetes Knowledge and Metabolic Control in Type 1 Diabetes Starting With Continuous Glucose Monitoring: FUTURE-PEAK.

PURPOSE: To investigate whether diabetes knowledge and health literacy impact glycemic control after 1 year of intermittently scanned continuous glucose monitoring (isCGM) in people with type 1 diabetes  ≥ 16 years. METHODS: In this prospective real-world cohort study, we assessed diabetes knowledge using a new 10-item questionnaire [Patient Education and Knowledge (PEAK)] and health literacy using the validated 6-item Newest-Vital Sign-D (NVS-D) questionnaire. Primary endpoint was association between PEAK score and change in hemoglobin A1c (HbA1c). Secondary endpoints were link between NVS-D score and change in HbA1c and that between time spent in/above/below range and PEAK/NVS-D scores. RESULTS: 851 subjects were consecutively recruited between July 2016 and July 2018. Median PEAK score was 8 (range: 0-10), and median NVS-D score was 6 (range 0-6). HbA1c evolved from 7.9% (7.8%-8.0%), 63 (62-64) mmol/mol, at start to 7.7% (7.6%-7.7%), 61 (60-61) mmol/mol (P < 0.001), at 6 months and to 7.8% (7.7%-7.9%), 62 (61-63) mmol/mol, at 12 months (P < 0.001). HbA1c only improved in subgroups with higher scores [PEAK subgroups with score 7-8 (P = 0.005) and 9-10 (P < 0.001) and NVS-D score 4-6 (P < 0.001)]. At 12 months, time spent below 70 mg/dL was reduced by 15% (P < 0.001), and time spent below 54 mg/dL was reduced by 14% (P < 0.001), irrespective of PEAK/NVS-D score. Multiple linear regression analysis demonstrated an association of PEAK score, scan frequency, and baseline HbA1c with evolutions in time in range and time in hyperglycemia. CONCLUSIONS: isCGM reduced time in hypoglycemia, and HbA1c evolved favorably. Our findings suggest that diabetes and health literacy affect glucometrics, emphasizing the importance of education.

Antenatal Depression and Risk of Gestational Diabetes, Adverse Pregnancy Outcomes, and Postpartum Quality of Life.

AIMS: To determine the impact of depressive symptoms on pregnancy outcomes and postpartum quality of life in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). METHODS: 1843 women from a prospective cohort study received universal GDM screening with an oral glucose tolerance test (OGTT). The Center for Epidemiologic Studies-Depression questionnaire was completed before GDM diagnosis was communicated and in GDM women in early postpartum. All participants completed the 36-Item Short Form Health Survey (SF-36) health survey postpartum. RESULTS: Women who developed GDM (231; 12.5%) had significantly more often depressive symptoms than NGT (1612; 87.5%) women [21.3% (48) vs 15.1% (239), odds ratio (OR) 1.52, 95% confidence interval (CI) (1.08-2.16), P = 0.017]. Compared to GDM women without depressive symptoms, depressed GDM women attended less often the postpartum OGTT [68.7% (33) vs 87.6% (155), P = 0.002], remained more often depressed [37.1% (13) vs 12.4% (19), P < 0.001], and had lower SF-36 scores postpartum. There were no significant differences in pregnancy outcomes between both groups. Rates of labor inductions were significantly higher in the NGT group with depressive symptoms compared to the nondepressed NGT group [31.7% (75) vs 24.7% (330), adjusted OR (aOR) 1.40, 95% CI (1.01-1.93), P = 0.041]. NGT women with depressive symptoms had lower SF-36 scores (P < 0.001) postpartum compared to nondepressed NGT women. CONCLUSIONS: Women with antenatal symptoms of depression develop more often GDM. GDM women with depressive symptoms remain more often depressed postpartum with lower quality of life. NGT women with depressive symptoms have higher rates of labor inductions and lower quality of life postpartum compared to nondepressed NGT women.

Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women.

AIMS: To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m2) normal glucose-tolerant women (NGT). METHODS: Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study. RESULTS: Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only. CONCLUSION: Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

Women with Mild Fasting Hyperglycemia in Early Pregnancy Have More Neonatal Intensive Care Admissions.

AIMS: To determine impact of mild fasting hyperglycemia in early pregnancy (fasting plasma glucose [FPG] 5.1-5.5 mmol/L) on pregnancy outcomes. METHODS: We measured FPG at 11.9 ± 1.8 weeks in 2006 women from a prospective cohort study. Women with FPG ≥5.6 mmol/L (19) received treatment and were excluded from further analyses. A total of 1838 women with FPG <5.6 mmol/L received a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. RESULTS: Of all participants, 78 (4.2%) had FPG 5.1 to 5.5 mmol/L in early pregnancy, of which 49 had a normal OGTT later in pregnancy (high fasting normal glucose tolerance [NGT] group). Compared with the NGT group with FPG <5.1 mmol/L in early pregnancy (low fasting NGT group, n = 1560), the high fasting NGT group had a higher body mass index (BMI), higher insulin resistance with more impaired insulin secretion and higher FPG and 30 minute glucose levels on the OGTT. The admission rate to neonatal intensive care unit (NICU) was significantly higher in the high fasting NGT group than in the low fasting NGT group (20.4% [10] vs 9.3% [143], P = .009), with no difference in duration (7.0 ± 8.6 vs 8.4 ± 14.3 days, P = .849) or indication for NICU admission between both groups. The admission rate to NICU remained significantly higher (odds ratio 2.47; 95% confidence interval 1.18-5.19, P = .017) after adjustment for age, BMI, and glucose levels at the OGTT. CONCLUSIONS: When provision of an OGTT is limited such as in the Covid-19 pandemic, using FPG in early pregnancy could be an easy alternative to determine who is at increased risk for adverse pregnancy outcomes.

Estimating the risk of gestational diabetes mellitus based on the 2013 WHO criteria: a prediction model based on clinical and biochemical variables in early pregnancy.

AIMS: We aimed to develop a prediction model based on clinical and biochemical variables for gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. METHODS: A total of 1843 women from a Belgian multi-centric prospective cohort study underwent universal screening for GDM. Using multivariable logistic regression analysis, a model to predict GDM was developed based on variables from early pregnancy. The performance of the model was assessed by receiver-operating characteristic (AUC) analysis. To account for over-optimism, an eightfold cross-validation was performed. The accuracy was compared with two validated models (van Leeuwen and Teede). RESULTS: A history with a first degree relative with diabetes, a history of smoking before pregnancy, a history of GDM, Asian origin, age, height and BMI were independent predictors for GDM with an AUC of 0.72 [95% confidence interval (CI) 0.69-0.76)]; after cross-validation, the AUC was 0.68 (95% CI 0.64-0.72). Adding biochemical variables, a history of a first degree relative with diabetes, a history of GDM, non-Caucasian origin, age, height, weight, fasting plasma glucose, triglycerides and HbA1c were independent predictors for GDM, with an AUC of the model of 0.76 (95% CI 0.72-0.79); after cross-validation, the AUC was 0.72 (95% CI 0.66-0.78), compared to an AUC of 0.67 (95% CI 0.63-0.71) using the van Leeuwen model and an AUC of 0.66 (95% CI 0.62-0.70) using the Teede model. CONCLUSIONS: A model based on easy to use variables in early pregnancy has a moderate accuracy to predict GDM based on the 2013 WHO criteria.

Characteristics and pregnancy outcomes across gestational diabetes mellitus subtypes based on insulin resistance.

AIMS/HYPOTHESIS: This study aimed to determine the characteristics and pregnancy outcomes across different subtypes of gestational diabetes mellitus (GDM) based on insulin resistance. METHODS: GDM subtypes were defined in 1813 pregnant women from a multicentre prospective cohort study, stratified according to insulin resistance, based on Matsuda index below the 50th percentile of women with normal glucose tolerance (NGT), during a 75 g OGTT at 24-28 weeks' gestation. GDM was diagnosed in 12.4% (n = 228) of all participants based on the 2013 WHO criteria. RESULTS: Compared with women with NGT (1113 [61.4%] of the total cohort) and insulin-sensitive women with GDM (39 [17.1%] women with GDM), women with GDM and high insulin resistance (189 [82.9%] women with GDM) had a significantly higher BMI, systolic BP, fasting plasma glucose (FPG), fasting total cholesterol, LDL-cholesterol and triacylglycerol levels in early pregnancy. Compared with women with NGT, insulin-sensitive women with GDM had a significantly lower BMI but similar BP, FPG and fasting lipid levels in early pregnancy. Compared with women with NGT, women with GDM and high insulin resistance had higher rates of preterm delivery (8.5% vs 4.7%, p = 0.030), labour induction (42.7% vs 28.1%, p < 0.001), Caesarean section (total Caesarean sections: 28.7% vs 19.4%, p = 0.004; emergency Caesarean sections: 16.0% vs 9.7%, p = 0.010), neonatal hypoglycaemia (15.4% vs 3.5%, p < 0.001) and neonatal intensive care unit admissions (16.0% vs 8.9%, p = 0.003). In multivariable logistic regression analyses using different models to adjust for demographics, BMI, FPG, HbA1c, lipid levels and gestational weight gain in early pregnancy, preterm delivery (OR 2.41 [95% CI 1.08, 5.38]) and neonatal hypoglycaemia (OR 4.86 [95% CI 2.04, 11.53]) remained significantly higher in women with GDM and high insulin resistance compared with women with NGT. Insulin-sensitive women with GDM had similar pregnancy outcomes as women with NGT. The need for insulin treatment during pregnancy and the rate of glucose intolerance in the early postpartum period were not significantly different among the GDM subtypes. CONCLUSIONS/INTERPRETATION: GDM with high insulin resistance represents a more adverse metabolic profile with a greater risk of adverse pregnancy outcomes.

Risk factor screening for gestational diabetes mellitus based on the 2013 WHO criteria

Objective: Since many European countries use risk factor screening for gestational diabetes mellitus (GDM), we aimed to determine the performance of selective screening for GDM based on the 2013 WHO criteria. Design and Methods: Overall, 1811 women received universal screening with a 75 g oral glucose tolerance test (OGTT) with GDM in 12.5% (n = 231) women based on the 2013 WHO criteria. We retrospectively applied different European selective screening guidelines to this cohort and evaluated the performance of different clinical risk factors to screen for GDM. Results: By retrospectively applying the English, Irish, French and Dutch guidelines for selective screening, respectively 28.5% (n = 526), 49.7% (n = 916), 48.5% (n = 894) and 50.7% (n = 935) had at least one risk factor, with GDM prevalence of respectively 6.5% (n = 120), 7.9% (n = 146), 8.0% (n = 147) and 8.4% (n = 154). Using maternal age ≥30 and/or BMI ≥25 for screening, positive rate was 69.9% (n = 1288), GDM prevalence 10.2% (n = 188), sensitivity 81.4% (CI: 75.8­86.2%) and specificity 31.8% (CI: 29.5­34.1%). Adding other clinical risk factors did not improve detection. GDM women without risk factors had more neonatal hypoglycemia (14.4 vs 4.0%, P = 0.001) and labor inductions (39.7 vs 25.9%, P = 0.020) than normal-glucose tolerant women, and less cesarean sections than GDM women with risk factors (13.8 vs 31.0%, P = 0.010). Conclusions: By applying selective screening by European guidelines, about 50% of women would need an OGTT with the lowest number of missed cases (33%) by the Dutch guidelines. Screening with age ≥30 years and/or BMI ≥25, reduced the number of missed cases to 18.6% but 70% would need an OGTT.

Prediction of Glucose Intolerance in Early Postpartum in Women with Gestational Diabetes Mellitus Based on the 2013 WHO Criteria.

Predictors for glucose intolerance postpartum were evaluated in women with gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. 1841 women were tested for GDM in a prospective cohort study. A postpartum 75g oral glucose tolerance test (OGTT) was performed in women with GDM at 14 ± 4.1 weeks. Of all 231 mothers with GDM, 83.1% (192) had a postpartum OGTT of which 18.2% (35) had glucose intolerance. Women with glucose intolerance were more often of Asian origin [15.1% vs. 3.7%, OR 4.64 (1.26⁻17.12)], had more often a recurrent history of GDM [41.7% vs. 26.7%, OR 3.68 (1.37⁻9.87)], higher fasting glycaemia (FPG) [5.1 (4.5⁻5.3) vs. 4.6 (4.3⁻5.1) mmol/L, OR 1.05 (1.01⁻1.09)], higher HbA1c [33 (31⁻36) vs. 32 (30⁻33) mmol/mol, OR 4.89 (1.61⁻14.82)], and higher triglycerides [2.2 (1.9⁻2.8) vs. 2.0 (1.6⁻2.5) mmol/L, OR 1.00 (1.00⁻1.01)]. Sensitivity of glucose challenge test (GCT) ≥7.2 mmol/l for glucose intolerance postpartum was 80% (63.1%⁻91.6%). The area under the curve to predict glucose intolerance was 0.76 (0.65⁻0.87) for FPG, 0.54 (0.43⁻0.65) for HbA1c and 0.75 (0.64⁻0.86) for both combined. In conclusion, nearly one-fifth of women with GDM have glucose intolerance postpartum. A GCT ≥7.2 mmol/L identifies a high risk population for glucose intolerance postpartum.

A Modified Two-Step Screening Strategy for Gestational Diabetes Mellitus Based on the 2013 WHO Criteria by Combining the Glucose Challenge Test and Clinical Risk Factors.

This study determines if a modified two-step screening strategy with a glucose challenge test (GCT) ≥ 7.2 mmol/L and clinical risk factors improves the diagnostic accuracy for gestational diabetes mellitus (GDM), based on 2013 WHO criteria, while limiting the number of oral glucose tolerance tests (OGTT). This was a prospective multicentric cohort study with 1811 participants receiving both GCT and 75 g OGTT in pregnancy. Participants and health care providers were blinded for GCT. Characteristics were analyzed across four glucose tolerance groups: abnormal (≥7.2 mmol/L), GCT GDM (n = 165), normal GCT GDM (n = 63), abnormal GCT normal glucose tolerant (NGT) (n = 472); normal GCT NGT (n = 1113). Compared to normal GCT NGT women, normal GCT GDM women had increased rates of obesity (23.8% vs. 10.5%, p < 0.001), ethnic minority background (19.3% vs. 8.2%, p < 0.001) and a history of GDM (13.8% vs. 4.6%, p = 0.03). By combined screening of GCT ≥ 7.2 mmol/L with these risk factors, sensitivity increased to respectively, 74.1⁻78.1% using one risk factor, and to 82.9% using any of these risk factors with a specificity of 57.5%. By using a modified two-step screening strategy, the number of women needing both a GCT and OGTT would be reduced to 25.5%, and 52.6% of all OGTTs could be avoided, compared to a universal one-step approach.