Is the Development of Gestational Diabetes Associated With the ABO Blood Group/Rhesus Phenotype?

Aims: There are few published data on the putative association between the ABO blood group/rhesus (Rh) factor and the risk of developing gestational diabetes mellitus (GDM). Our aim was to explore the link between each one factor and GDM development. Methods: All women having given birth at Lille University Medical Center (Lille, France) between August 1st, 2017, and February 28th, 2018, were tested for GDM, using the method recommended in the French national guidelines. The risk of GDM was assessed for each ABO blood group, each Rh phenotype and combinations thereof, using logistic regression models. Results: 1194 women had at least one GDM risk factor. The percentage of GDM varied with the ABO group (p=0.013). Relative to group O women, group AB women were more likely to develop GDM (OR = 2.50, 95% CI [1.43 to 4.36], p=0.001). Compared with the Rh-positive O group, only the Rh-positive AB group had an elevated risk of developing GDM (OR = 3.02, 95% CI [1.69 to 5.39], p < 0.001). Conclusions: Our results showed that Rh-positive group AB women have a greater risk of GDM. With a view to preventing GDM, at-risk individuals could be identified by considering the ABO blood group phenotype either as a single risk factor or in combination with other risk factors.

Effects of COVID-19 pandemic lockdown on gestational diabetes mellitus: A retrospective study.

OBJECTIVE: The objective of our study was to evaluate the impact of the lockdown period on the glycemic balance in patients with GDM. METHODS: A retrospective study in one center (Lille, France) compared two periods: the COVID-19 lockdown of 18 March 2020 to 7 May 2020 versus the same period during 2019. Glucose targets were defined by a capillary fasting glucose target < 5.1mmol/L and/or a 2-hour postprandial capillary glucose < 6.6 mmol/L. GDM control was defined as: good (< 20% of the glycemic values were not within the target range), acceptable (20 to 40% of the glycemic values were not within the target range) or poor (> 40% of the glycemic values were not within the target range). RESULTS: Two hundred twenty-nine patients were included in 2019 and 222 in 2020. The same mean number of capillary blood sugar tests was performed by the two groups. Postprandial blood sugar was significantly less well controlled in 2020, with a lower rate of good control (61.6% vs 69.4%) and higher rates of acceptable (24.7% vs 21.8%) and poor control (13.7% and 8.7%) (p < 0.05). Use of insulin therapy was significantly higher in 2020 compared with 2019 (47.7% and 36.2%, respectively; p < 0.05). CONCLUSION: Diabetes control was lower during the COVID-19 pandemic lockdown, even if follow-up was not impacted. This may be explained by reduced physical activity, modified dietary habits and anxiety during this period.

[Screening for gestational diabetes: Still many unsolved issues]. / Le dépistage du diabète gestationnel : encore de nombreuses questions non résolues.

For many years, there is a debate on gestational diabetes screening, including what screening test and thresholds to use. The purpose of this literature review is to determine whether gestational diabetes screening in France meets the 10 definition criteria of the WHO. The DG is a public health problem, with a natural history partially known and detectable at an early stage. Currently, there is no data showing that there is a benefit to treat patient screens by the new criteria. The one-step approach-screening test can only detect fetal complications and not maternal complications. It seems to be acceptable for the population of pregnant women. The diagnostic test and treatment also seem to be acceptable to us. To this day, its reproducibility is uncertain. Screening leads to an increase in obstetric interventions. Several studies found that screening for gestational diabetes is cost-effective but in a different context of care than in France.

Outcome of twin pregnancies associated with glucose intolerance.

OBJECTIVES: There is little information about the impact of hyperglycaemia in twin pregnancies. The objective of our study was to evaluate the maternal, foetal and neonatal complications in patients with twin pregnancy and glucose intolerance defined by gestational diabetes mellitus and gestational mild hyperglycaemia. STUDY DESIGN: We performed a single-centre retrospective study. Screening for gestational diabetes was achieved by a two-step method. Patients were managed according to the French guidelines. After matching for age and body mass index, outcomes were compared in 177 patients with glucose intolerance and 509 controls. Macrosomia was defined as birth weight above the 90th percentile of gestational age adjusted for parity, foetal sex and maternal biometrics. RESULTS: Prevalence of glucose intolerance was 17.5% in our population. Complications of pregnancy and mode of delivery were similar between the two groups. Caesarean section was associated with age >35 years, vascular complications of pregnancy and non-cephalic presentation of the first twin. Rate of macrosomia was not different between the two groups. The only risk factor for macrosomia was a history of macrosomia in a previous pregnancy (odds ratio = 5.9, 95% confidence interval = 1.8-19.2). CONCLUSION: Twin pregnancies complicated by glucose intolerance were not associated with an increased risk of macrosomia or Caesarean section. Further studies should assess the value of screening gestational diabetes mellitus in twin pregnancies.

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes.

INTRODUCTION/OBJECTIVES: The role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic. The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls. METHODS: PRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n=8) at delivery and compared to controls (n=5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n=5) or nicotinamide (NCT) plus STZ (n=9) or vehicle (n=9). Placental whole-genome gene expression and PRL western blots were performed at birth. RESULTS: In human placentas, PRL (p<0.05) and BMP-1 (p<0.01) gene expressions were increased with a higher amount of cleaved PRL (p<0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT-STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p<0.01) and Bmp-1 (p<0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p<0.05) and NCT-STZ (p<0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women. CONCLUSIONS: Alterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.

[Impact of the new screening criteria on the gestational diabetes prevalence]. / Impact des nouveaux critères de dépistage sur la prévalence du diabète gestationnel.

BACKGROUND: To evaluate the impact of the new IADPSG thresholds on gestational diabetes mellitus (GDM) prevalence. METHODS: Universal screening for GDM was performed in 200 consecutive patients at 24 to 28 weeks with 75 g oral glucose tolerance test. RESULTS: The prevalence of GDM was 14.0%. We observed that among the 28 patients with GDM, 16 (57.1%) had only one abnormal value, 10 (35.7%) two abnormal values and only two (7.2%) had three abnormal values. For the 16 patients with one abnormal value, 13 of them (81.2%) have an abnormal fasting plasma glucose (FPG). Patients with GDM had an increased body mass index (29.6 kg/m(2) vs 25.1 kg/m(2), P<0.001) and more important rates of familial history of type II diabetes (46.4% vs 21.5%, P<0.005) and history of GDM in a previous pregnancy (21.4% vs 2.9%, P<0.002) compared to non-GDM patients. Birth weight was increased in offspring of mothers with GDM (3451.3g vs 3387.4 g, P<0.05). CONCLUSION: Our study found an increased rate of GDM with the new IADPSG criteria compared to previous published data. Higher rates of GDM represent a challenge for the organization of perinatal teams involved in GDM care.

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.

Prediction of macrosomia by serial sonographic measurements of fetal soft-tissues and the liver in women with pregestational diabetes.

OBJECTIVES: This study aimed to determine whether antenatal ultrasound measurements of fetal soft-tissues and liver can predict macrosomia in women with pregestational diabetes. METHODS: Fetal biometry, soft-tissue thickness (anterior abdominal wall [STAW], thigh [STT], upper arm [STA], scapular [STS]) and liver size were measured sonographically at 23, 28, 31 and 34 weeks of gestation. Large for gestational age (LGA) was defined as a birth weight greater than 90th percentile for gestational age on standard curves adjusted for maternal height and weight, parity and fetal gender. The area (±standard error) under receiver operating characteristic (AUROC) curves were also calculated. RESULTS: A total of 29 pregnant women with pregestational diabetes were included, and a total of 663 measurements taken. Fifteen neonates were LGA. There was no significant difference in fetal soft-tissue thickness at 23, 28 and 31 weeks between the LGA and non-LGA neonates. In contrast, at 34 weeks, fetal soft-tissues were significantly thicker in LGA neonates (P<0.05), but with no difference in liver surface area between the two groups. The specificity and sensitivity of 34-week ultrasonography to detect macrosomia was 78.6% and 66.7%, respectively, for abdominal circumference (AC), 71.4% and 93.3% for STT, 85.7% and 80.0% for STA, and 71.4% and 86.7% for STAW. No parameter was more powerful than the others. The best AUROC curves were found for AC (0.807), STT (0.821), STA (0.855) and STAW (0.821). CONCLUSION: Third-trimester sonographic measurements of fetal soft-tissue may help to detect macrosomia in pregnancies complicated by pregestational diabetes.

Placental expression of the obesity-associated gene FTO is reduced by fetal growth restriction but not by macrosomia in rats and humans.

Genetic variants in the FTO (fat mass- and obesity-associated) gene have the highest association of all obesity-associated genes. Its placental expression was shown to relate to birth weight, suggesting that it may participate in the control of fetal weight gain. To gain more insight into the implication of FTO in fetal growth, we measured its placental expression in samples including extremes of abnormal fetal growth, such as after intrauterine growth restriction (IUGR) or macrosomia in both rats and humans. In rats, fetal growth was modulated by maternal nutritional modifications. In humans, placental villi were collected from pathological pregnancies (i.e. with IUGR or fetal macrosomia). Placental FTO mRNA expression was reduced by IUGR but was not significantly affected by macrosomia in either rats or humans. Our data suggest that placental FTO may participate in interactions between the in utero environment and the control of fetal growth under IUGR conditions by modulating epigenetic processes.

Management of pregnancy in women with type 1 diabetes mellitus: guidelines of the French-Speaking Diabetes Society (Société francophone du diabète [SFD]).

AIM: The clinical guidelines reported by the French-Speaking Diabetes Society (Société francophone du diabète) include updated recommendations for preconceptual planning and care in the management of pregnancy in women with type 1 diabetes mellitus (T1DM). METHODS: The working group included diabetologists, as well as an obstetrician, a nurse and a dietician. A review of the literature was performed using PubMed and Cochrane databases. Guidelines published by foreign diabetes societies were also consulted. RESULTS: In women with T1DM, pregnancy increased the risks of hypoglycaemia, diabetic ketoacidosis, pregnancy-induced hypertension, infections and worsening of diabetic microvascular disease. Moreover, T1DM during pregnancy had an impact on the embryo and the fetus, and may have increased the risk of spontaneous miscarriages, malformations, premature births, and fetal and neonatal complications. However, intensive glycaemic control and preconceptual care have been shown to decrease the rate of fetal demise and malformations. Also, the use of insulin analogues during pregnancy is now regarded as safe. Tight glucose control and frequent follow-up are recommended throughout pregnancy in women with T1DM. Their obstetric management should take place in a maternity hospital with an appropriate perinatal environment and in close collaboration with diabetologists. CONCLUSION: Pregnancy planning and adequate management during pregnancy are mandatory for improving the outcomes of women with T1DM.

[Ketoacidosis complicated by fetal death revealing fulminant diabetes during the third trimester of pregnancy]. / Acidocétose compliquée d'une mort foetale révélant un diabète fulminant au troisième trimestre de grossesse.

We describe an acute onset of diabetes mellitus during third trimester of pregnancy revealed by ketoacidosis, complicated by fetal death, which could evoke fulminant type 1 diabetes, a novel subtype of type 1 diabetes first described in Japan and rarely described in Caucasian people. Diagnosis of diabetic ketoacidosis could be made on simple signs as abdominal pain, vomiting or ketone bodies on urinary multistix. Capillary glycaemic control is necessary to distinguish fast from ketoacidosis. The treatment of this severe imbalance must be initiated in emergency.

Placental BDNF/TrkB signaling system is modulated by fetal growth disturbances in rat and human.

The brain-derived neurotrophic factor (BDNF) has been shown to exert an important role during implantation, placental development, and fetal growth control in mice. Its expression is closely related to the nutritional status in several tissues such as in the nervous system. In a previous study, we demonstrated that maternal undernutrition (MU), during the perinatal life, modified both the BDNF and its functional receptor, the tyrosine kinase receptor B (TrkB) gene expression in the brain of growth-restricted rat offspring during sensitive developmental windows, suggesting that these early modifications may have long-lasting consequences. In the present study, we measured BDNF/TrkB mRNA and protein levels in rat placentas from mothers submitted to a 50% food restriction during gestation, and in human placentas from pregnancies with fetal growth restriction or fetal macrosomia. In the rat, two subtypes of placental TrkB receptors have been identified: the TrkB-FL and TrkB-T1 receptors. We found that MU induced intrauterine growth restriction (IUGR) of fetuses at term and decreased the placental BDNF mRNA and protein levels. Placentae from undernourished mothers exhibited an increased mRNA expression of TrkB-FL whereas both TrkB-FL and TrkB-T1 receptors proteins levels were not modified. In human IUGR placentas, both BDNF and TrkB receptor mRNA expressions were up-regulated. Finally, although neither BDNF nor TrkB mRNA levels were altered by fetal macrosomia alone, BDNF mRNA levels were decreased when macrosomia was associated with maternal type 1 diabetes. These results show that the placental BDNF/TrkB system is modulated in rats and humans during pregnancies with fetal growth perturbations and is affected by the maternal energetic status. These data suggest that this system may exert an important role for the feto-placental unit development and that it may also be implicated in the etiology of pathologies related to placental and fetal growth disturbances.

Treatment of diabetes mellitus using an external insulin pump: the state of the art.

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.

Treatment of diabetes mellitus using an external insulin pump in clinical practice.

Before the initiation of insulin pump therapy, patients must be aware of the different aspects of this form of intensive insulin therapy. Most healthcare professionals recommend a sequential approach to inform patients about CSII. Factors that need to be considered in choosing an insulin pump include its safety features, durability of the device, tolerability and comfort of the catheter, user-friendliness, technical features and appearance. The initial insulin requirements need to be individualized for the given patient, using different methods to determine the appropriate dosages for the basal rate and prandial boluses. Glycaemic targets and algorithms for insulin dose adaptation need to be learned by the patients to enable them to avoid and/or correct hypo- and hyperglycaemia/ketosis episodes. Patients are also advised on how to carry out frequent self-monitoring of blood glucose-and of ketone bodies, if necessary. Insulin pumps are now able to deliver a range of basal rates and boluses that increase the flexibility of CSII. One specific issue is the approach to meal-planning, based on carbohydrate-counting or the equivalent: this method of so-called 'flexible insulin therapy' can improve metabolic control (for instance, by diminishing postprandial excursions) as well as the quality of life of patients. Evaluation of the knowledge and practices of the patient can be made through a continuous educational programme carried out by experienced nurses and physicians at the start of therapy and during follow-up. In addition, it may be necessary to identify the reasons for lack of improvement in metabolic control after several months of therapy, which include pump malfunction, cannula problems, miscalculated insulin dosages and insufficient metabolic control in specific clinical situations with a high risk of metabolic deterioration (illness, exercise, concomitant drugs). Annual assessment of the patient using an itemized checklist is required to verify the continued efficacy and safety of insulin pump therapy, two main factors of success with CSII treatment.

Increasing incidence of abnormal glucose tolerance in women with prior abnormal glucose tolerance during pregnancy: DIAGEST 2 study.

AIMS: Mild blood glucose abnormalities during pregnancy may be linked to later glucose tolerance abnormalities or diabetes mellitus. Our aim was to determine the prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) 6.75 years after delivery in women with differential blood glucose status during pregnancy. METHODS: We compared long-term outcomes among control women (n = 221), women with abnormal glucose tolerance during pregnancy (AGT; n = 322) and women with gestational diabetes (GDM; n = 466) who participated in DIAGEST 1. Women were recruited from 15 public maternity units in France. Clinical parameters could be determined in 155 control, 220 AGT and 338 GDM subjects. Rates of DM, IGT, IFG and 'Any Abnormality' were compared between the groups (American Diabetes Association criteria). RESULTS: Adherence to follow-up was 70.7%. Rates of DM, IGT and IFG were respectively 0.9% DM, 2.1% IGT and 3.6% IFG in the control group; rates in the AGT group were 6.3%, 11.3% and 6.3%. In GDM women, the rates of DM, IGT and IFG were, respectively, 18.0%, 13.4% and 8.5%. Predictors for DM were previous GDM, medical history of hypertension, age at delivery > or = 33 years, family history of diabetes, fasting glucose during pregnancy > or = 5.5 mmol/l and the severity of hyperglycaemia during pregnancy defined by the number of abnormal blood glucose values fasting, 1, 2 and 3 h during the glucose tolerance test at diagnosis of GDM. CONCLUSION: This study has identified a high prevalence of glucose tolerance abnormalities after AGT during pregnancy. Compared with GDM women, women with AGT have an intermediate risk of later diabetes.

[Fifteen practical questions concerning gestational diabetes]. / Quinze questions pratiques concernant le diabète gestationnel.

With a review of the current literature, a clarification on screening and management of gestational diabetes is hereby set out, within the frame of a Clinical Expert Series. According to the ethnic group, the prevalence varies from 1 to 14%. The treatment is based on dietary advice, insulin. The ACHOIS study demonstrates that the treatment of gestational diabetes significantly decreases perinatal complications (4 to 1%). The place of the oral treatment (glyburide) remains to be defined. In most countries, diagnosis rests on oral glucose test tolerance: Sullivan 50 g glucose test (1 hour) and 100 g test of glucose if positive (3 hours); WHO 75 g test (2 hours). The screening can be systematic or only on risk factors (wide variations between studies). Screening of gestational diabetes is required because its management improves pregnancy outcomes. Despite this, there is no consensus on the strategy of screening and diagnosis.