Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial.

BACKGROUND: People with type 1 diabetes can continuously monitor their glucose levels on demand (intermittently scanned continuous glucose monitoring [isCGM]), or in real time (real-time continuous glucose monitoring [rtCGM]). However, it is unclear whether switching from isCGM to rtCGM with alert functionality offers additional benefits. Therefore, we did a trial comparing rtCGM and isCGM in adults with type 1 diabetes (ALERTT1). METHODS: We did a prospective, double-arm, parallel-group, multicentre, randomised controlled trial in six hospitals in Belgium. Adults with type 1 diabetes who previously used isCGM were randomly assigned (1:1) to rtCGM (intervention) or isCGM (control). Randomisation was done centrally using minimisation dependent on study centre, age, gender, glycated haemoglobin (HbA1c), time in range (sensor glucose 3·9-10·0 mmol/L), insulin administration method, and hypoglycaemia awareness. Participants, investigators, and study teams were not masked to group allocation. Primary endpoint was mean between-group difference in time in range after 6 months assessed in the intention-to-treat sample. This trial is registered with ClinicalTrials.gov, NCT03772600. FINDINGS: Between Jan 29 and Jul 30, 2019, 269 participants were recruited, of whom 254 were randomly assigned to rtCGM (n=127) or isCGM (n=127); 124 and 122 participants completed the study, respectively. After 6 months, time in range was higher with rtCGM than with isCGM (59·6% vs 51·9%; mean difference 6·85 percentage points [95% CI 4·36-9·34]; p<0·0001). After 6 months HbA1c was lower (7·1% vs 7·4%; p<0·0001), as was time <3·0 mmol/L (0·47% vs 0·84%; p=0·0070), and Hypoglycaemia Fear Survey version II worry subscale score (15·4 vs 18·0; p=0·0071). Fewer participants on rtCGM experienced severe hypoglycaemia (n=3 vs n=13; p=0·0082). Skin reaction was more frequently observed with isCGM and bleeding after sensor insertion was more frequently reported by rtCGM users. INTERPRETATION: In an unselected adult type 1 diabetes population, switching from isCGM to rtCGM significantly improved time in range after 6 months of treatment, implying that clinicians should consider rtCGM instead of isCGM to improve the health and quality of life of people with type 1 diabetes. FUNDING: Dexcom.

Lipohypertrophy Monitoring Study (LIMO): Effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: Confirmation of an unpleasant truth.

AIMS: To investigate whether single use of 4 mm needles combined with education about injection technique and lipohypertrophy affects HbA1c, hypoglycaemia and glucose variability. METHODS: Insulin-injecting people with diabetes recruited from nine Belgian diabetes centres were prospectively followed for 6 months. They were provided 4 mm pen needles and education concerning injection technique using an online platform (BD and Me™) based on the international Forum for Injection Technique & Therapy Recommendations focused on avoidance of lipohypertrophy zones and reduction of needle reuse. RESULTS: A total of 171 people with diabetes were included of which 146 completed the study. At baseline, lipohypertrophy was present in 63.0% of those who completed the study, with 51.4% injecting in zones of lipohypertrophy, 37.0% incorrectly rotating and 95.9% reusing needles. After the intervention, 7.5% still injected in a lipohypertrophy zone, 4.1% rotated incorrectly and needle reuse decreased to 21.2%. The number of participants with severe hypoglycaemias (from 15.8% to 4.1%, p < 0.001), unexplained hypoglycaemias (from 46.6% to 16.4%, p < 0.001) and high glucose variability (from 64.4% to 29.5%, p < 0.001) was significantly reduced. HbA1c and total daily insulin dose remained stable. CONCLUSION: The combination of 4 mm pen needles and online education on injection techniques significantly reduced the number of people with severe hypoglycaemic episodes, unexplained hypoglycaemia and high glucose variability but did not improve HbA1c control nor lower insulin needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04659330.

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.

The Belgian Diabetes in Pregnancy Study (BEDIP-N), a multi-centric prospective cohort study on screening for diabetes in pregnancy and gestational diabetes: methodology and design.

BACKGROUND: The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommends universal screening with a 75 g oral glucose tolerance test (OGTT) using stricter criteria for gestational diabetes (GDM). This may lead to important increases in the prevalence of GDM and associated costs, whereas the gain in health is unclear. The goal of 'The Belgian Diabetes in Pregnancy Study' (BEDIP-N) is to evaluate the best screening strategy for pregestational diabetes in early pregnancy and GDM in an ethnically diverse western European population. The IADPSG screening strategy will be followed, but in addition risk questionnaires and a 50 g glucose challenge test (GCT) will be performed, in order to define the most practical and most cost effective screening strategy in this population. METHODS: BEDIP-N is a prospective observational cohort study in 6 centers in Belgium. The aim is to enroll 2563 pregnant women in the first trimester with a singleton pregnancy, aged 18-45 years, without known diabetes and without history of bariatric surgery. Women are universally screened for overt diabetes and GDM in the first trimester with a fasting plasma glucose and for GDM between 24-28 weeks using the 50 g GCT and independently of the result of the GCT, all women will receive a 75 g OGTT using the IADPSG criteria. Diabetes and GDM will be treated according to a standardized routine care protocol. Women with GDM, will be reevaluated three months postpartum with a 75 g OGTT. At each visit blood samples are collected, anthropometric measurements are obtained and self-administered questionnaires are completed. Recruitment began in April 2014. DISCUSSION: This is the first large, prospective cohort study rigorously assessing the prevalence of diabetes in early pregnancy and comparing the impact of different screening strategies with the IADPSG criteria on the detection of GDM later in pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02036619. Registered 14-1-2014.

Impact of breastfeeding on risk of glucose intolerance in early postpartum after gestational diabetes.

Aims: To determine the impact of breastfeeding on the risk of postpartum glucose intolerance in women with gestational diabetes. Methods: Sub-analysis of two multi-centric prospective cohort studies (BEDIP-N and MELINDA) in 1008 women with gestational diabetes. Data were collected during pregnancy and at a mean of 12 weeks postpartum. Multivariate logistic regression was used to estimate the effect of breastfeeding on glucose intolerance, with adjustment for ethnicity, education, income, professional activity and BMI. Results: Of all participants, 56.3% (567) breastfed exclusively, 10.1% (102) gave mixed milk feeding and 33.6% (339) did not breastfeed. Mean breastfeeding duration was 3.8 ± 2.4 and 3.7 ± 2.1 months in the breastfeeding and mixed milk feeding groups (p=0.496). The rate of glucose intolerance was lower in both the breastfeeding [22.3% (126)] and mixed milk feeding [25.5% (26)] groups compared to the no breastfeeding group [29.5% (100)], with an adjusted OR of 0.7 (95% CI 0.5-1.0) for glucose intolerance in the breastfeeding group compared to no breastfeeding group and an adjusted OR of 0.7 (95% CI 0.4-1.2) for the mixed milk feeding group compared to the no breastfeeding group. Postpartum, breastfeeding women had a lower BMI, less often postpartum weight retention, lower fasting triglycerides, less insulin resistance and a higher insulin secretion-sensitivity index-2 than the mixed milk feeding and no breastfeeding group. The mixed milk feeding group was more often from an non-White background, had a lower blood pressure and lower fasting triglycerides compared to the no breastfeeding group. Conclusions: Breastfeeding (exclusive and mixed milk feeding) is associated with less glucose intolerance and a better metabolic profile in early postpartum in women with gestational diabetes.

Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial.

BACKGROUND: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous glucose monitoring (rtCGM) with alert functionality offers additional benefits to adults with type 1 diabetes. The extension of the randomised ALERTT1 trial assessed the effect of switching from isCGM to rtCGM up to 24 months. METHODS: In this 6-month, double-arm, parallel-group, non-masked, randomised, controlled trial, done across six hospitals in Belgium, 254 adults aged 18 years or older with type 1 diabetes previously using isCGM were randomly assigned (1:1) to rtCGM with alerts (intervention; n=127) or isCGM without alerts (control; n=127). Upon completion of the 6-month trial, the control group switched to rtCGM (is-rtCGM group), and the intervention group continued rtCGM (rt-rtCGM group). The extension focused on within-group changes in time in range (TIR; 3·9-10·0 mmol/L; primary outcome), HbA1c, time in clinically significant hypoglycaemia (<3·0 mmol/L), and Hypoglycaemia Fear Survey worry (HFS-worry) score (all prespecified key secondary outcomes). Mean within-group change versus the start of rtCGM is reported, with a positive value referring to a lower value at start of rtCGM. This trial is registered at ClinicalTrials.gov (NCT03772600). FINDINGS: 119 participants were assigned to the is-rtCGM group of whom 112 (94%) completed the 24-month trial, and 123 participants were assigned to the rt-rtCGM group of whom 117 (95%) completed the 24-month trial. TIR increased from 51·8% (95% CI 49·1-54·5) at start of rtCGM (month 6) to 63·5% (60·7-66·3) at month 12 in the is-rtCGM group, and remained stable up to month 24 (change 11·7 percentage points [pp] [9·4-14·0; p<0·0001). In the rt-rtCGM group, TIR increased from 52·5% (95% CI 49·8-55·1) at start of rtCGM (month 0) to 63·0% (60·3-65·8) at month 12, also remaining stable up to month 24 (change 10·5 pp [8·2-12·8]; p<0·0001). HbA1c decreased from 7·4% (57 mmol/mol; month 6) to 6·9% (52 mmol/mol) at month 24 (change -0·54 pp [95% CI -0·64 to -0·44]; -5 mmol/mol [95% CI -6 to -4]; p<0·0001) in the is-rtCGM group, and from 7·4% (57 mmol/mol; month 0) to 7·0% (53 mmol/mol) at month 24 (change -0·43 pp [95% CI -0·53 to -0·33]; -4 mmol/mol [95% CI -5 to -3]; p<0·0001) in the rt-rtCGM group. The change in HFS-worry score was -2·67 (month 24 vs month 6; p=0·0008) in the is-rtCGM group and -5·17 points (month 24 vs month 0; p<0·0001) in the rt-rtCGM group. Time in clinically significant hypoglycaemia was unchanged in both groups after month 12. Severe hypoglycaemia decreased from 31·0 to 3·3 per 100 patient-years after switching to rtCGM. INTERPRETATION: Glycaemic control and hypoglycaemia worry improved significantly up to 24 months after switching from isCGM without alerts to rtCGM with alerts, supporting the use of rtCGM in the care of adults with type 1 diabetes. FUNDING: Dexcom.

The Belgian Diabetes in Pregnancy Follow-Up Study (BEDIP-FUS): A Multi-Centric Prospective Cohort Study on the Long-Term Metabolic Risk across Different Degrees of Gestational Glucose Intolerance: Methodology and Design.

The Belgian Diabetes in Pregnancy follow-up study (BEDIP-FUS) aims to investigate the impact of body mass index (BMI), adiposity and different degrees of glucose intolerance on the metabolic profile and future risk for type 2 diabetes (T2D) in women and offspring five years after delivery in the BEDIP study. The BEDIP study was a prospective cohort study to evaluate different screening strategies for gestational diabetes (GDM) based on the 2013 WHO criteria. The aim of the BEDIP-FUS is to recruit 375 women-offspring pairs, stratified according to three different subgroups based on the antenatal result of the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during the BEDIP pregnancy. The follow-up visit consists of a 75 g OGTT, anthropometric measurements and questionnaires for the mothers, and a fasting blood sample with anthropometric measurements for the child. Primary outcome for the mother is glucose intolerance defined by the American Diabetes Association criteria and for the offspring the BMI z-score. Recruitment began in January 2021. The BEDIP-FUS study will help to better individualize follow-up in women with different degrees of hyperglycemia in pregnancy and their offspring.

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.

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.

The Impact of Baseline User Characteristics on the Benefits of Real-Time Versus Intermittently Scanned Continuous Glucose Monitoring in Adults With Type 1 Diabetes: Moderator Analyses of the ALERTT1 Trial.

BACKGROUND: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others. METHODS: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with P < .10 in the univariable analysis were combined into a single model. RESULTS: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c (P = .0059), indicating less worries with rtCGM in people with baseline HbA1c <6.5% or ≥8%. Given P < .10 for dependency of delta TIR on insulin therapy type (favoring multiple daily injections), baseline HbA1c, and baseline TIR, these variables were combined into a multivariable analysis; interactions were not statistically significant. CONCLUSIONS: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D.

Relationship Between Time in Range, Glycemic Variability, HbA1c, and Complications in Adults With Type 1 Diabetes Mellitus.

PURPOSE: Real-time continuous glucose monitoring (RT-CGM) provides information on glycemic variability (GV), time in range (TIR), and guidance to avoid hypoglycemia, thereby complimenting HbA1c for diabetes management. We investigated whether GV and TIR were independently associated with chronic and acute diabetes complications. METHODS: Between September 2014 and January 2017, 515 subjects with type 1 diabetes using sensor-augmented pump therapy were followed for 24 months. The link between baseline HbA1c and CGM-derived glucometrics (TIR [70-180 mg/dL], coefficient of variation [CV], and SD) obtained from the first 2 weeks of RT-CGM use and the presence of complications was investigated. Complications were defined as: composite microvascular complications (presence of neuropathy, retinopathy, or nephropathy), macrovascular complications, and hospitalization for hypoglycemia and/or ketoacidosis. RESULTS: Individuals with microvascular complications were older (P < 0.001), had a longer diabetes duration (P < 0.001), a higher HbA1c (7.8 ± 0.9 vs 7.5 ± 0.9%, P < 0.001), and spent less time in range (60.4 ± 12.2 vs 63.9 ± 13.8%, P = 0.022) compared with those without microvascular complication. Diabetes duration (odds ratio [OR] = 1.12 [1.09-1.15], P < 0.001) and TIR (OR = 0.97 [0.95-0.99], P = 0.005) were independent risk factors for composite microvascular complications, whereas SD and CV were not. Age (OR = 1.08 [1.03-1.14], P = 0.003) and HbA1c (OR = 1.80 [1.02-3.14], P = 0.044) were risk factors for macrovascular complications. TIR (OR = 0.97 [0.95-0.99], P = 0.021) was the only independent risk factor for hospitalizations for hypoglycemia or ketoacidosis. CONCLUSIONS: Lower TIR was associated with the presence of composite microvascular complications and with hospitalization for hypoglycemia or ketoacidosis. TIR, SD, and CV were not associated with macrovascular complications.

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.

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.

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.

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.

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.

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.

Screening and follow-up of pregestational diabetes and gestational diabetes mellitus: A survey of primary care physicians in Belgium.

AIMS: Consensus regarding the best screening and follow-up strategy for gestational diabetes mellitus (GDM) is lacking, resulting in heterogeneity in clinical practice. We aimed to evaluate screening and follow-up practices for pregestational type 2 diabetes (T2DM) and GDM in primary care in Belgium. METHODS: We performed an online survey among primary care physicians (PCPs) in the northern part of Belgium, Flanders. RESULTS: Responses were obtained from 379 PCPs. Approximately two thirds of participants estimated the prevalence of pregestational T2DM and GDM in Flanders at 5% and <10%, respectively. The risk of developing T2DM within 10 years after a history of GDM was estimated at <30% by nearly half of all participants. The majority of interviewed PCPs screen for pre-existing T2DM and GDM. For T2DM, fasting glycaemia was used by 92.2% whereas for GDM, 75.2% used the 50g glucose challenge test (GCT). Fasting glycaemia was the preferred test for postpartum follow-up. CONCLUSIONS: While overall guideline adherence appears favourable, the prevalence of GDM is underestimated. Increased awareness on the long-term risk for women with a history of GDM is needed. The overall preference for the two-step strategy with GCT indicates that the 2019 Flemish guidelines on GDM screening are attainable in primary care.

Sustained Impact of Real-time Continuous Glucose Monitoring in Adults With Type 1 Diabetes on Insulin Pump Therapy: Results After the 24-Month RESCUE Study.

OBJECTIVE: In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH). RESEARCH DESIGN AND METHODS: This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA1c, with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up. RESULTS: After 24 months, HbA1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P < 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P < 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA1c <7% (<53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P < 0.0001). CONCLUSIONS: Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH.