Hyperglycemia In Early Pregnancy Research Articles

Intermediate hyperglycemia in early pregnancy: A South Asian perspective

"Intermediate hyperglycemia in early pregnancy (IHEP)" refers to mild hyperglycemia detected before 24 gestational weeks (GW), satisfying the criteria for the diagnosis of gestational diabetes mellitus. Many professional bodies recommend routine screening for "overt diabetes" in early pregnancy, which identifies a significant number of women with mild hyperglycemia of undetermined significance. A literature search revealed that one-third of GDM women in South Asian countries are diagnosed before the conventional screening period of 24 GW to 28 GW; hence, they belong in the IHEP category. Most hospitals in this region diagnose IHEP by oral glucose tolerance test (OGTT) using the same criteria used for GDM diagnosis after 24 GW. There is some evidence to suggest that South Asian women with IHEP are more prone to adverse pregnancy events than women with a diagnosis of GDM after 24 GW, but this observation needs to be proven by randomized control trials. Fasting plasma glucose is a reliable screening test for GDM that can obviate the need for OGTT for GDM diagnosis among 50% of South Asian pregnant women. HbA1c in the first trimester predicts GDM in later pregnancy, but it is not a reliable test for IHEP diagnosis. There is evidence to suggest that HbA1c in the first trimester is an independent risk factor for several adverse pregnancy events. Further research to identify the patho-genetic mechanisms behind the fetal and maternal effects of IHEP is strongly recommended.

Reducing Maternal Obesity and Diabetes Risks Prior to Conception with the National Diabetes Prevention Program.

Intrauterine exposure to maternal obesity and hyperglycemia greatly increases offspring health risks. Scalable lifestyle interventions to lower weight and glycemia prior to conception are needed, but have been understudied, especially in diverse and low-income women with disproportionately high risks of negative maternal-child outcomes. The objective of this report is to provide initial evidence of the National Diabetes Prevention Program's (NDPP) effects on maternal-child outcomes in diverse, low-income women and their offspring. The yearlong NDPP was delivered in a safety net healthcare system to 1,569 participants from 2013 to 2019. Using medical records, we evaluated outcomes for women < 40 years who became pregnant and delivered after attending the NDPP for ≥ 1 month (n = 32), as compared to a usual care group of women < 40 years (n = 26) who were initially eligible for the NDPP but were excluded due to pregnancy at enrollment. Most women in either group were Latinx, had Medicaid or were uninsured, and had obesity at baseline. The mean difference in BMI change from baseline to conception was - 1.8 ± 0.6kg/m2 (p = 0.002) for NDPP versus usual care. Fewer NDPP participants had obesity at conception (56.7% vs. 88.0%, p = 0.011) and hyperglycemia in early pregnancy (4.0% vs. 25.0%; p = 0.020) than usual care. No other differences were statistically significant, yet nearly all outcomes favored the NDPP. Covariate-adjusted results were consistent, except the difference in frequency of obesity at conception was no longer significant (p = 0.132). Results provide preliminary evidence that the NDPP may support a reduction in peri-conceptional obesity/diabetes risks among diverse and low-income women.

Gestational Diabetes- An Endocrinologist’s Perspective

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy today. As per the American Diabetes Association (ADA) 2022, the latest definition of GDM is diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. Blood sugar more than normal and less than diabetes in the first trimester is defined as hyperglycemia in early pregnancy. GDM has been associated with adverse pregnancy effects and outcomes such as preeclampsia, macrosomia, large for gestational age (LGA), shoulder dystocia, stillbirth, as well as neonatal complications. Dietary counseling and physical activity are the primary treatment for GDM. If sugar is not controlled through diet and exercise, metformin and or insulin are other treatment options.

Frequency of preeclampsia spectrum disorders by diabetes subgroup

We aim to determine the frequency of preeclampsia (PE) spectrum disorders among subjects with diabetes by subtype: Type 1 diabetes mellitus (T1DM); Type 2 DM (T2DM); gestational diabetes diet controlled (A1GDM); medication controlled GDM (A2GDM); and hyperglycemia in early pregnancy. We hypothesized a higher rate of PE with severe features among those with T1DM and T2DM.

Early-Pregnancy Intermediate Hyperglycemia and Adverse Pregnancy Outcomes Among Women Without Gestational Diabetes

ContextUniversal early-pregnancy screening for overt diabetes reveals intermediate hyperglycemia (fasting plasma glucose [FPG] [5.1-6.9 mM]).ObjectiveWe evaluated the association between early-pregnancy intermediate hyperglycemia and adverse pregnancy outcomes among women without gestational diabetes.MethodsThis retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, from 2013 to 2017. All singleton pregnancies with FPG less than or equal to 6.9 mM in early pregnancy and receiving a 75-g oral glucose tolerance test (OGTT) were included. Women with prepregnancy diabetes were excluded. Individuals with normal OGTT were analyzed. Pregnancy outcomes for FPG less than 5.1 mM and intermediate hyperglycemia were evaluated. The primary outcomes were large for gestational age (LGA) and primary cesarean delivery. Multivariate logistic regressions were conducted. Statistical significance was defined as P less than .05.ResultsIn total, 24 479 deliveries were included, of which 23 450 (95.8%) had normal OGTTs later in pregnancy (NGT). There were 807 (3.4%) women who had an FPG of 5.1 to 6.9 mM in early pregnancy. Compared to the NGT group with an FPG of less than 5.1 mM in early pregnancy (N = 20692), the intermediate hyperglycemia NGT group (N = 693) had a higher age and body mass index (BMI), and significantly higher rates of LGA, primary cesarean delivery, preterm birth, preeclampsia, and neonatal distress. The rates of primary cesarean delivery (adjusted odds ratio [AOR] 1.24; 95% CI, 1.05-1.45), preterm birth (AOR 1.75; 95% CI, 1.29-2.36), and neonatal distress (AOR 3.29; 95% CI, 1.57-6.89) remained statistically significantly higher after adjustments for maternal age, BMI, and other potential confounding factors.ConclusionWomen with intermediate hyperglycemia in early pregnancy are at an increased risk for adverse maternal-fetal outcomes, even with normal future OGTTs.

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

AimsTo determine impact of mild fasting hyperglycemia in early pregnancy [fasting plasma glucose (FPG) (5.1-5.5mmol/l)] on pregnancy outcomes.MethodsWe measured FPG at 11.9 ±1.8 weeks in 2006 women from a prospective cohort study. Women with FPG ≥5.6mmol/l (19) received treatment and were excluded from further analyses. 1838 women with FPG <5.6mmol/l received a 75g oral glucose tolerance test (OGTT) between 24-28 weeks of pregnancy.ResultsOf all participants, 78 (4.2%) had FPG 5.1-5.5mmol/l in early pregnancy, of which 49 had a normal OGTT later in pregnancy [high fasting normal glucose tolerance (NGT) group]. Compared to 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 BMI, higher insulin resistance with more impaired insulin secretion and higher FPG and 30 min glucose levels on the OGTT. The admission rate to neonatal intensive care unit (NICU) was significantly higher in the high fasting NGT group compared to the low fasting NGT group [20.4% (10) vs. 9.3% (143), p=0.009], with no difference in duration (7.0±8.6 vs. 8.4±14.3 days, p= 0.849) or indication for NICU admission between both groups. The admission rate to NICU remained significantly higher [OR 2.47 (95% CI 1.18-5.19), p=0.017] after adjustment for age, BMI and glucose levels at the OGTT.ConclusionsWhen 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.

Diagnostic accuracy of random plasma glucose and random blood capillary glucose in detecting international association of diabetes and pregnancy study groups- defined hyperglycemia in early pregnancy.

Maternal hyperglycemia first diagnosed in pregnancy, previously referred to as gestational diabetes mellitus is associated with health consequences for both the mother and her fetus/baby, not only in the short term but also in the long term. Early screening helps to identify women with overt diabetes or those with early onset GDM. The aim of this study was to determine the diagnostic performance of two screening tests (Random plasma glucose, Random capillary glucose) in relation to 75g Oral glucose tolerance test (OGTT) done before 24 weeks gestation. This prospective longitudinal cohort study was carried out between 1st February, 2017 and 31st July, 2017, at two teaching hospitals in Nigeria. Two hundred and eighty one (281) pregnant women who met the inclusion criteria were selected and screened with both random plasma glucose (RPG) and random capillary glucose (RCG) before 24 weeks of pregnancy. They were then made to undergo 75g OGTT a week later. The diagnostic performance of the screening tests were determined. A total of 270 women had 75g OG. Random plasma glucose and Random capillary glucose performed poorly compared to 75g-OGTT in detecting hyperglycemia in early pregnancy.

Progress in Development of Interventions to Prevent Birth Defects in Diabetic Pregnancies

Diabetic embryopathy is a diabetic complication, in which maternal hyperglycemia in early pregnancy causes birth defects in newborn infants. Under maternal diabetic conditions, hyperglycemia disturbs intracellular molecular activities and organelles functions. These include protein misfolding in the endoplasmic reticulum (ER), overproduction of reactive oxygen species (ROS) in mitochondria, and high levels of nitric oxide (NO). The resultant ER, oxidative, and nitrosative stresses activate apoptotic machinery to cause cell death in the embryo, ultimately resulting in developmental malformations. Based on the basic research data, efforts have been made to develop interventional strategies to alleviate the stress conditions and to reduce embryonic malformations. One of the challenges in birth defect prevention is to identify effective and safe agents to be used in pregnancy. One approach is to search and characterize naturally occurring phytochemicals, including flavonoids, curcuminoids and stilbenoids, for use in prevention of diabetic embryopathy.

Treating hyperglycemia in early pregnancy: a randomized controlled trial

Treating women with gestational diabetes mellitus in the third trimester improves perinatal outcomes. It is unknown whether treating women with mild glucose intolerance earlier in pregnancy would be beneficial in the reduction of maternal and neonatal morbidities. In women with hyperglycemia (hemoglobin A1c ≥5.7% and/or fasting glucose ≥92 mg/dL) in early pregnancy, we sought to determine whether immediate treatment improved maternal and neonatal outcomes. This unblinded randomized controlled trial enrolled women with hyperglycemia at ≤15+0 weeks gestation between 2013 and 2015. Participants were assigned randomly to early pregnancy or third-trimester treatment of hyperglycemia that included nutrition counseling, glucose monitoring, and medications as needed. Participants underwent a blinded 2-hour glucose tolerance test at 24-28 weeks gestation. Exclusion criteria were pregestational diabetes mellitus and multiple gestations. The primary outcome was the proportion of infants with neonatal umbilical cord C-peptide >1.77 nmoL (90th percentile). Secondary outcomes were neonatal fat mass, infant World Health Organization weight-for-length percentile at birth, maternal gestational weight gain, and diagnosis of gestational diabetes mellitus on glucose tolerance test. Mann-Whitney-Wilcoxon test and Fisher's exact test were used, as appropriate. A total of 202 women were assigned randomly; 45 women dropped out before delivery, which left cases 157 for analysis (82 with early pregnancy and 75 with third-trimester treatment). The trial was terminated early because of low enrollment. Baseline characteristics were similar between groups. There was no difference in C-peptide >90th percentile between groups (1 [1.5%] vs 4 [6.7%]; P=.19) in the early pregnancy and third-trimester groups, respectively). There was also no difference in fat mass (0.37±0.16 vs 0.36±0.17 kg; P=.91), weight-for-length percentile at birth (25% vs 25%; P=.46), or macrosomia (1.5 vs 5.0%; P=.84). Maternal gestational weight gain was 22.6±12.9 lb and 23.9±11.2 lb in the early pregnancy and third-trimester groups, respectively (P=.88). Gestational diabetes mellitus was diagnosed in 19.0% of the cohort and did not differ between groups (14.2% vs 25.8%; P=.17). In this population of women with hyperglycemia, treatment in early pregnancy did not appear to improve maternal or neonatal outcomes significantly. Given comparable results in both groups, caution should be used in the initiation of an intensive diabetes mellitus treatment protocol for women with the diagnosis of hyperglycemia in early gestation.

Controversies and Advances in Gestational Diabetes-An Update in the Era of Continuous Glucose Monitoring.

Diabetes in pregnancy, both preexisting type 1 or type 2 and gestational diabetes, is a highly prevalent condition, which has a great impact on maternal and fetal health, with short and long-term implications. Gestational Diabetes Mellitus (GDM) is a condition triggered by metabolic adaptation, which occurs during the second half of pregnancy. There is still a lot of controversy about GDM, from classification and diagnosis to treatment. Recently, there have been some advances in the field as well as recommendations from international societies, such as how to distinguish previous diabetes, even if first recognized during pregnancy, and newer diagnostic criteria, based on pregnancy outcomes, instead of maternal risk of future diabetes. These new recommendations will lead to a higher prevalence of GDM, and important issues are yet to be resolved, such as the cost-utility of this increase in diagnoses as well as the determinants for poor outcomes. The aim of this review is to discuss the advances in diagnosis and classification of GDM, as well as their implications in the field, the issue of hyperglycemia in early pregnancy and the role of hemoglobin A1c (HbA1c) during pregnancy. We have looked into the determinants of the poor outcomes predicted by the diagnosis by way of oral glucose tolerance tests, highlighting the relevance of continuous glucose monitoring tools, as well as other possible pathogenetic factors related to poor pregnancy outcomes.

Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with this statin when used during early pregnancy in humans and animals.

Congenital Pituitary Gland Abnormalities—A Possible Association With Maternal Hyperglycemia: Two Case Reports

Congenital hypopituitarism (CH) occurs in 1 in 100 000 live births.1 Genetic factors, hypoperfusion, and environmental changes in utero may play causative roles.2 Maternal diabetes mellitus (DM) in relation to other congenital central nervous system abnormalities such as neural tube defects (NTDs) and hydrocephalus have been described, but an association between hyperglycemia in utero and pituitary formation has, to our knowledge, not been reported.3 We present 2 infants with CH, both born to mothers with hyperglycemia in early pregnancy. Both infants' pituitary glands are structurally identical; each has a hypoplastic anterior pituitary, an ectopic posterior pituitary located at the base of the third ventricle, and an absent pituitary stalk.

Troponin T and Pro–B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

OBJECTIVECardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function.RESEARCH DESIGN AND METHODSThis was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester.RESULTSFetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05).CONCLUSIONSBiochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

Risk of Minor and Major Fetal Malformations in Diabetics with High Haemoglobin A1c Values in Early Pregnancy

The incidence of congenital malformations is about three times higher in infants of insulin-dependent diabetic mothers than in the general population. The exact cause of this increase is not known, but experimental and clinical data show an association between congenital malformations and maternal hyperglycemia in early pregnancy, the critical period with regard to fetal malformations. The present authors report an association between the severity of maternal hyperglycemia in early pregnancy, as measured by blood hemoglobin A1c values, and the occurrence of fetal malformations in mothers with insulin-dependent diabetes. Between April 1978 and December 1982, the maternal hemoglobin A1c values had been determined at least once before the end of the 15th week of gestation in 139 insulin-dependent diabetic patients who gave birth after 24 weeks of gestation. In addition, a fetal malformation was observed in each of three cases of induced abortion in which early hemoglobin A1c determinations had been carried out. Pregnancies were classified as 1) not complicated by malformation, 2) complicated by minor malformation, and 3) complicated by major malformation. A malformation was classified as major if it was fatal or likely to cause serious handicap to the child. Other malformations were classified as minor. A total of 125 pregnancies were not complicated by fetal malformation. A malformed fetus or infant was observed in each of 17 pregnancies. In six cases, the anomalies were classified as minor, and in 11 cases they were classified as major. The mean initial hemoglobin A1c value was significantly higher in the group with minor malformations (9.3 per cent, with an SD of 1.9 per cent) and in the group with major malformations (9.6 per cent; SD, 1.8 per cent) than in the group without malformations (8.0 per cent; SD, 1.4 per cent) (P < 0.05 and P < 0.001, respectively). The difference in hemoglobin A1c values between the groups with minor and major malformations was not significant. In all of the 17 pregnancies complicated by malformation, the mean initial hemoglobin A1c value was 9.5 per cent (SD, 1.8 per cent), which was significantly higher (P < 0.001) than in the group without malformation. There was a significant positive relationship (x2 = 11.9; P = 0.001) between the maternal hemoglobin A1c value in early pregnancy and the occurrence of malformation. An initial hemoglobin A1c value of 10.0 per cent or more was associated with malformations in six of 17 pregnancies (35.3 per cent). Two of these were minor (11.8 per cent) and four were major (23.5 per cent) malformations. An intermediate hemoglobin Alc value (8.0–9.9 per cent) was associated with malformations in eight of 62 pregnancies (12.9 per cent). Relatively low initial hemoglobin A1c values, i.e., below 8.0 per cent, were associated with malformations in only three of 63 pregnancies (4.8 per cent).