Differences in newborn screening results among women with gestational diabetes mellitus

Multiple studies undertaken on cord blood demonstrate analyte perturbations in infants exposed to gestational diabetes mellitus (GDM). Cord blood as a sample is influenced by maternal and placental metabolism. Newborn screening (NBS), performed after the first 24 hours of life reflects ea rly neonatal metabolism. We compared NBS analytes between women wi th and wi thout GDM with different management approaches in the Treatment of Booking of Gestational Diabetes (TOBOGM) pilot randomised controlled trial. Pregnant women with GDM risk factors were randomised to early or deferred GDM treatment following an oral glucose tolerance test (<20 weeks gestation). Women without GDM served as “decoys”. From the decoy group 11 developed GDM (screened at 26-28 weeks), were analysed separately; their results were compared with the other groups. De-identified controls were chosen from NBS results from the same analytic run matched for sex, birthweight and gestational age. Results were available for 73/78 women participating in the pilot and 358 de-identified controls. Tyrosine levels (μmol/l; whole blood)were higher in the late GDM group vs early, deferred treatment, and decoy groups (medians:106.28; IQR: 96.73-151.11) (76.33; 64.64-97.90) (75.68; 66.59-110.88)(73.74; 58.32-90.36) (p=0.009) and remained elevated when compared to normal, age-matched controls (106.28; 96.73-151.11) (87.26; 68.55-111.26) (p value=0.01) Immunoreactive trypsinogen (μgm/l; whole blood)was highest in the early treatment group when compared with group-specific controls (22.30; 13.90–29.90 vs 14.00, 10.60–21.10) (p=0.02). These results provide evidence of biochemical perturbations detectable on NBS of in-utero exposure to hyperglycemia and treatment and provide data for hypothesis building

Effectiveness of integrated diabetes care interventions involving diabetes specialists working in primary and community care settings : systematic review and meta-analysis

Introduction: Evidence that integrated diabetes care interventions can substantially improve clinical outcomes is mixed. However, previous systematic reviews have not focussed on clinical effectiveness where the endocrinologist was actively involved in guiding diabetes management. Methods: We searched EMBASE, COCHRANE, MEDLINE, SCOPUS, CINAHL, Google Scholar databases and grey literature published in English language up to 25 January 2021. Reviewed articles included Randomised Controlled Trials (RCTs) and pre-post studies testing the effectiveness on clinical outcomes after ≥6 months intervention in non-pregnant adults (age ≥ 18 years) with type 1 or type 2 diabetes mellitus. Two reviewers independently extracted data and completed a risk of bias assessment. Appropriate meta-analyses for each outcome from RCTs and pre-post studies were performed. Heterogeneity was assessed using the I2 statistic and Cochran’s Q and publication bias assessed using Doi plots. Studies were not pooled to estimate the cost-effectiveness as the cost outcomes were not comparable across trials/studies. Results: We reviewed 4 RCTs and 12 pre-post studies. The integrated care model of diabetes specialists working with primary care health professionals had a positive impact on HbA1c in both RCTs and pre-post studies and on systolic blood pressure, diastolic blood pressure, total cholesterol and weight in pre-post studies. In the RCTs, interventions reduced HbA1c (–0.10% [–0.15 to –0.05]) (–1.1 mmol/mol [–1.6 to –0.5]), versus control. Pre-post studies demonstrated improvements in HbA1c (–0.77% [–1.12 to –0.42]) (–8.4 mmol/mol [–12.2 to –4.6]), systolic blood pressure (–3.30 mmHg [–5.16 to –1.44]), diastolic blood pressure (–3.61 mmHg [–4.82 to –2.39]), total cholesterol (–0.33 mmol/L [–0.52 to –0.14]) and weight (–2.53 kg [–3.86 to –1.19]). In a pre-post study with no control group only 4% patients experienced hypoglycaemia after one year of intervention compared to baseline. Conclusions: Integrated interventions with an active endocrinologist involvement can result in modest improvements in HbA1c, blood pressure and weight management. Although the improvements per clinical outcome are modest, there is possible net improvements at a holistic level

The ADIPS pilot national diabetes in pregnancy benchmarking programme

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy

Screening and treatment for early-onset gestational diabetes mellitus : a systematic review and meta-analysis

Purpose of Review: We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) Recent Findings: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24–28 weeks’ gestation. Summary: A high proportion (15–70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM

A perspective on the accuracy of blood glucose meters during pregnancy

Blood glucose monitoring is fundamental for hyperglycemia management during pregnancy, but are the devices up to the job? Studies assessing the accuracy of 10 commercially available glucose meters during pregnancy showed that although >98–99% of the meter values were in the acceptable zones of the error grid for the majority of the meters, the meter performance varied, with the majority showing positive bias and a few showing minimal negative bias. The mean difference between meter and laboratory plasma values varied between −0.33 and 0.73 mmol/L. Three meters showed deviations from laboratory results with a change in maternal hematocrit levels. No meters had a total analytical error 24 h), and a lower incidence of neonatal hypoglycemia. The flash glucose monitoring system shows good accuracy in pregnant women but has not been marketed widely in the U.S. We suggest that meters cannot be assumed to be sufficiently accurate during pregnancy and that manufacturers should ensure a total error <5%, with bias and imprecision <2% during pregnancy. Large studies are needed to evaluate the usefulness of CGMS among pregnant women with type 2 diabetes and gestational diabetes mellitus

Pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy in an urban New Zealand population and their association with postnatal HbA1c uptake

Background: Adverse pregnancy outcomes are more common in women with hyperglycaemia. Many women have suboptimal uptake of HbA1c testing postdelivery. Aims: To compare pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy, and their association with postnatal HbA1c uptake after the introduction of email reminders. Materials and Methods: A retrospective and prospective single-centre study was conducted in South Auckland in 2639 women with early gestational diabetes mellitus (GDM) (diagnosed < 20 weeks), late GDM (diagnosed ≥ 20 weeks), overt diabetes in pregnancy, or known type 2 diabetes (T2DM) during pregnancy. Automated email reminders were sent to general practitioners to increase postnatal HbA1c screening. Results: HbA1c during pregnancy increased across the late GDM (n = 1425), early GDM (n = 148), overt diabetes (n = 573) and T2DM (n = 493) groups (P < 0.001). Stillbirth was least common in the late GDM group (0, 0.7, 0.5, and 1.9%, respectively, P < 0.001), as were caesarean delivery (32.7, 45.1, 39.4, and 53.5%, respectively P < 0.001), large for gestational age (LGA) (14.7, 18.2, 22.3, and 30.5%, respectively, P < 0.001), small for gestational age (8.8, 16.7, 11.0, and 11.1%, respectively, P = 0.02), and preeclampsia/eclampsia (7.7, 9.2, 13.0, and 14.8%, respectively, P < 0.001). LGA and preeclampsia/eclampsia were more common among Pacific and Māori women than European women (LGA, 30.1, 22.7, 10.3%, respectively, P < 0.001; preeclampsia/eclampsia, 13.5, 14.0, and 8.1%, respectively, P < 0.001). Postpartum HbA1c screening increased among women with GDM/overt diabetes after the introduction of the reminder emails (39.6% vs 34.0%, P = 0.03). Conclusions: Women with late GDM are least likely to experience adverse outcomes. Email reminders to improve postpartum HbA1c screening warrant further investigation

Newborn screening samples for diabetes research : an underused resource

Inborn errors of metabolism and diabetes share common derangements in analytes of metabolic networks that are tested for in newborn screening, usually performed 48–72 h after birth. There is limited research examining the metabolic imprint of diabetes on newborn screening results. This paper aims to demonstrate the links between diabetes, biochemical genetics and newborn screening in investigating disease pathophysiology in diabetes, provide possible reasons for the lack of research in diabetes in newborn screening and offer recommendations on potential research areas. We performed a systematic search of the available literature from 1 April 1998 to 31 December 2018 involving newborn screening and diabetes using OVID, MEDLINE, Cochrane and the PROSPERO register, utilizing a modified extraction tool adapted from Cochrane. Eight studies were included after screening 1312 records. Five studies reanalyzed dried blood spots (DBS) on filter paper cards, and three studies utilized pre-existing results. The results of these studies and how they relate to cord blood studies, the use of cord blood versus newborn screening dried blood spots as a sample and considerations on newborn screening and diabetes research is further discussed. The timing of sampling of newborn screening allows insight into neonatal physiology in a catabolic state with minimal maternal and placental influence. This, combined with the wide coverage of newborn screening worldwide, may aid in our understanding of the origins of diabetes

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes

Aims: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. Methods: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012–2014). In women with a BMI ≥29 kg/m2, insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. Results: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50–7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20–4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. Conclusions: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both