A comparison of the safety and effectiveness of insulin aspart with other bolus insulins in women with pre-existing Type 1 diabetes during pregnancy: A post hoc analysis of a prospective cohort study.

AIMS: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. METHODS: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. RESULTS: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). CONCLUSIONS: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

Diabetes mellitus in pregnancy across Canada.

BACKGROUND: Contemporary estimates of diabetes mellitus (DM) rates in pregnancy are lacking in Canada. Accordingly, this study examined trends in the rates of type 1 (T1DM), type 2 (T2DM) and gestational (GDM) DM in Canada over a 15-year period, and selected adverse pregnancy outcomes. METHODS: This study used repeated cross-sectional data from the Canadian Institute of Health Information (CIHI) hospitalization discharge abstract database (DAD). Maternal delivery records were linked to their respective birth records from 2006 to 2019. The prevalence of T1DM, T2DM and GDM were calculated, including relative changes over time, assessed by a Cochrane-Armitage test. Also assessed were differences between provinces and territories in the prevalence of DM. RESULTS: Over the 15-year study period, comprising 4,320,778 hospital deliveries in Canada, there was a statistically significant increase in the prevalence of GDM and T1DM and T2DM. Compared to pregnancies without DM, all pregnancies with any form of DM had higher rates of hypertension and Caesarian delivery, and also adverse infant outcomes, including major congenital anomalies, preterm birth and large-for-gestational age birthweight. CONCLUSION: Among 4.3 million pregnancies in Canada, there has been a rise in the prevalence of DM. T2DM and GDM are expected to increase further as more overweight women conceive in Canada.

Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing.

AIMS/HYPOTHESIS: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management. METHODS: We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021. RESULTS: In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks. CONCLUSIONS/INTERPRETATION: Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.

Association of Vaspin levels and its SNP rs2236242 with Gestational Diabetes at a tertiary care setting : RESEARCH ARTICLE.

OBJECTIVE: To evaluate and correlate vaspin levels and genotype frequency in gestational diabetes mellitus. METHODS: The case-control study was conducted at Aga Khan University, Karachi, from November 2015 to December 2016, and comprised pregnant women in their second trimester with gestational diabetes mellitus. Healthy pregnant women with similar characteristics were enrolled as the control group. Tetra arms amplification system for vaspin gene was performed. SPSS 21 was used for data analysis. RESULTS: Of the 112 pregnant women, 67(60%) were normo-glycaemic and 45(40%) had gestational diabetes. Those with gestational diabetes had a higher body mass index (p=0.047) and fasting blood glucose levels (p<0.01). Serum vaspin concentrations were significantly lower in the healthy group compared to the diabetics (p=0.041). Genotype and allele frequencies followed Hardy Weinberg's Equilibrium but no significant differences were observed in genotype distribution between the groups (p>0.05).. CONCLUSIONS: Higher serum vaspin levels were seen in gestational diabetic females, but genotype and allele frequencies showed no association of vaspin with gestational diabetes mellitus.

Screening and diagnosis of gestational diabetes mellitus.

American Diabetes Association defines gestational diabetes mellitus (GDM) as diabetes which is diagnosed in the 2nd or 3rd trimester of pregnancy and is not clearly overt diabetes. GDM, if missed or not treated properly can result in maternal and foetal complications, short as well as long term. Screening for overt diabetes, especially for high risk women should be done at the earliest in pregnancy and for GDM, universally at 24-28 weeks of gestation. One step screening by IADPSG (75 gram OGTT), has been recently adopted by most of professional bodies to achieve uniformity. IADPSG criteria have resulted in increase in prevalence of GDM, and consequently increase pressure on health care services as well as on patients. This has resulted in discordance of view on universal adoption of the criteria. Many feel this criteria results in over diagnosis without clear benefits. This brief review will provide the answers to some of the important questions pertaining to screening for GDM.

Management of labour in pregnancy complicated by diabetes.

Diabetes mellitus complicates <5% of all pregnancies in Pakistan, but is a major cause of perinatal morbidity and mortality, as well as maternal morbidity. Appropriate glycaemic control is not only important throughout pregnancy but is equally important during the intra-partum period. Increased blood glucose levels 4-6 hours prior to delivery increase the chances of hypoglycaemia in neonates. It is essential to optimize blood glucose levels during the intra-partum period as avoiding maternal hyperglycaemia will prevent foetal hyperglycaemia, and hence reduce the chances of neonatal hypoglycaemia and foetal acidaemia. Infants who develop neonatal hypoglycaemia, have a 2-3.5 times higher risk of developing neuro-developmental impairment on follow-up at 18 months to 7 years of age.

Ambulatory glucose profile: Flash glucose monitoring.

Ambulatory glucose profile (AGP) is a novel way of assessing glycaemic levels on a 24 hour basis, through a minimally invasive method, known as flash glucose monitoring. This review describes the unique features of AGP, differentiates it from existing methods of glucose monitoring, and explains how it helps pursue the glycaemic pentad. The review suggests pragmatic usage of this technology, including pre-test, intra-test, and post-test counselling, and lists specific clinical scenarios where the investigation seems to be of immense benefit.

Skin Autofluorescence in Young Adult Offspring of Women with Type 1 Diabetes: A Cross-Sectional Case-Control Study.

INTRODUCTION: Offspring born to women with type 1 diabetes pregnancies have an elevated risk for early-onset obesity and type 2 diabetes compared with offspring born to women without diabetes. Skin autofluorescence (SAF) is a marker of accumulated advanced glycation end products (AGEs) and it has been shown to predict type 2 diabetes, cardiovascular disease, and mortality in the general population. The aim of this study was to evaluate whether maternal type 1 diabetes influences the SAF value in young adult offspring. METHODS: This cross-sectional case-control study included 78 offspring of women with type 1 diabetes (cases) and 85 control participants (controls). All study participants, aged 18-23 years, were invited to participate in a clinical assessment including laboratory tests and questionnaires. SAF was assessed using the AGE reader from the dominant forearm of each participant. RESULTS: The mean SAF value did not differ between the cases (1.61 [standard deviation (SD) 0.37]) arbitrary units [AU]) and the controls (1.64 [SD 0.41] AU) (p = 0.69). After adjusting for glycated hemoglobin A1c, body fat percentage, smoking, and season the mean SAF value did not differ between the cases and the controls (p = 0.49) but differed between men and women (p = 0.008), without any interaction observed (p = 0.78). CONCLUSION: SAF values did not differ between the young adult offspring of women with type 1 diabetes and offspring born to mothers without diabetes. Surprisingly, young adult women showed higher SAF values than men in both case and control groups.

Managing Diabetes in Pregnancy Before, During, and After COVID-19.

Background: Pregnant women with diabetes are identified as being more vulnerable to the severe effects of COVID-19 and advised to stringently follow social distancing measures. Here, we review the management of diabetes in pregnancy before and during the lockdown. Methods: Majority of antenatal diabetes and obstetric visits are provided remotely, with pregnant women attending hospital clinics only for essential ultrasound scans and labor and delivery. Online resources for supporting women planning pregnancy and for self-management of pregnant women with type 1 diabetes (T1D) using intermittent or continuous glucose monitoring are provided. Retinal screening procedures, intrapartum care, and the varying impact of lockdown on maternal glycemic control are considered. Alternative screening procedures for diagnosing hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) are discussed. Case histories describe the remote initiation of insulin pump therapy and automated insulin delivery in T1D pregnancy. Results: Initial feedback suggests that video consultations are well received and that the patient experiences for women requiring face-to-face visits are greatly improved. As the pandemic eases, formal evaluation of remote models of diabetes education and technology implementation, including women's views, will be important. Conclusions: Research and audit activities will resume and we will find new ways for supporting pregnant women with diabetes to choose their preferred glucose monitoring and insulin delivery.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study.

AIM: To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. METHODS: A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n=135), including a viewed-DVD subgroup (n=58), were compared with an historical cohort (pre-DVD, n=114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. RESULTS: Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8mmol/mol]; p=0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8mmol/mol], P<0.001; planned pregnancy (88% vs. 59%, P<0.001); taken folic acid preconception (81% vs. 43%, P=0.001); and had HbA1c recorded preconception (88% vs. 53%, P<0.001) than the pre-DVD cohort. CONCLUSIONS: Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Gestational diabetes mellitus: Where are we now?

Gestational diabetes mellitus (GDM) is defined as any carbohydrate intolerance first diagnosed during pregnancy. The prevalence of GDM is about 2-5% of normal pregnancies and depends of the prevalence of same population to type 2 diabetes mellitus. It is associated with adverse outcome for the mother, the fetus, neonate, child and adult offspring of the diabetic mother. Detection of GDM lies on screening, followed as necessary by diagnostic measures. Screening can either be selective, based upon risk stratification or universal. Timely testing enables the obstetrician to assess glucose tolerance in the presence of the insulin-resistant state of pregnancy and permits treatment to begin before excessive fetal growth has occurred. Once a diagnosis of GDM was made close perinatal surveillance is warranted. The goal of treatment is reducing fetal-maternal morbidity and mortality related with GDM. The exact glucose values needed are still not absolutely proved. The decision whether and when to induce delivery depends on gestational age, estimated fetal weight, maternal glycemic control and bishop score. Future research is needed regarding prevention of GDM, treatment goals and effectiveness of interventions, guidelines for pregnancy care and prevention of long term metabolic sequel for both the infant and the mother.