Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial.

OBJECTIVE: This study investigated if inositol in a combination of myo-inositol and D-chiro-inositol would prevent gestational diabetes mellitus (GDM) in women with a family history of diabetes. RESEARCH DESIGN AND METHODS: This was a randomized controlled trial that examined whether inositol from the first antenatal visit prevents GDM. The trial was carried out in a single-center tertiary referral center. Women with a family history of diabetes were enrolled at the first antenatal visit. They were randomized to the intervention group, which received a combination of 1,100 mg myo-inositol, 27.6 mg D-chiro-inositol, and 400 µg folic acid, or to the control group, which received 400 µg folic acid only. All women had an oral glucose tolerance test between 24 and 28 weeks' gestation. The primary end point was the incidence of GDM. Statistical analysis was carried out using SPSS Statistical Package version 20. RESULTS: Two hundred forty women, 120 in each arm, were recruited between January 2014 and July 2015. There were no differences in characteristics between the groups. The incidence of GDM was 23.3% (n = 28) in the intervention group compared with 18.3% (n = 22) in the control group (P = 0.34). The mean fasting plasma glucose at the glucose tolerance test was 81 mg/dL in both groups. CONCLUSIONS: Commencing an inositol combination in early pregnancy did not prevent GDM in women with a family history of diabetes. Further studies are required to examine whether inositol supplements at varying doses may prevent GDM.

Postpartum dyslipidaemia in women diagnosed with gestational diabetes mellitus.

BACKGROUND: Diabetes mellitus is a known risk factor for cardiovascular disease which should prompt screening for other cardiovascular risk factors, including dyslipidaemia. Women diagnosed with gestational diabetes mellitus (GDM) are not routinely screened for cardiovascular risk factors. AIMS: The objective of this study was to determine the prevalence of dyslipidaemia postpartum in women with GDM. METHODS: The study was performed in a large university hospital. Women with GDM had a fasting lipid profile performed 6 weeks postnatally. Clinical details were obtained from the medical records. Lipid results in our cohort were compared with healthy women of the same age. RESULTS: The overall prevalence of postpartum dyslipidaemia was 52 % (n = 51). Total cholesterol was raised in 44 % (n = 43), low-density lipoprotein was raised in 33 % (n = 32) and triglycerides were raised in 16 % (n = 16). Of the 51 women with dyslipidaemia, 73 % (n = 37) had more than one abnormality in their lipid profile. Four of the five women with an abnormal postpartum GTT had an abnormal lipid profile. Compared with healthy women of the same age, women with GDM had higher total cholesterol (p = 0.04), higher LDL (p = 0.003), higher triglycerides (p < 0.001) and lower HDL (p < 0.04). CONCLUSIONS: Women with GDM should be screened for dyslipidaemia postpartum and protective cardiovascular interventions offered where appropriate.

Heart rate variability in neonates of type 1 diabetic pregnancy.

BACKGROUND: Cardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. AIMS: Our aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. STUDY DESIGN AND SUBJECTS: This was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). OUTCOME MEASURES: Heart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. RESULTS: Neonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (p<0.05). This altered HRV was significantly related to fetal acidaemia, cord blood glucose values and maternal glycaemic control during pregnancy (p<0.05). CONCLUSION: Neonates of pregestational diabetic pregnancy have altered HRV which is related to maternal hyperglycaemia, fetal acidaemia and fetal glycaemia. Exposure of the developing heart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life.

The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young.

OBJECTIVE: Women with maturity-onset diabetes of the young (MODY) are often first identified and diagnosed with diabetes during pregnancy. Genetics and hyperglycemia play an important role in determining fetal size in MODY pregnancies. The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations. STUDY DESIGN: A retrospective chart review of 37 women with a GCK/HNF-1α mutation was conducted. Data on variables such as birthweight, mode of delivery, and the treatment of hyperglycemia were available on 89 pregnancies. RESULTS: The birthweight in unaffected GCK offspring was significantly higher than in the affected GCK offspring (4.8 [4.1-5.2] kg vs 3.2 [3.1-3.7] kg; P = .01). Seven-point home blood glucose monitoring over a 7-day period in each trimester demonstrated higher fasting and postprandial glycemic excursions in the first trimester of GCK pregnancies when compared to HNF-1α pregnancies (fasting 104 [90-115] mg/dL vs 84 [77-88] mg/dL; P = .01 and postprandial 154 [135-196] mg/dL vs 111 [100-131] mg/dL; P = .04) despite insulin treatment. There was a higher percentage of miscarriages in the GCK group when compared to the HNF-1α MODY group (33.3% vs 14%; P = .07), which was similar to the background population. Insulin initiated at an early gestation appeared to lower the incidence of macrosomia in GCK unaffected offspring. CONCLUSION: Hyperglycemia in HNF-1α pregnancies is easily managed with current insulin protocols; in contrast, glycemic excursions are difficult to manage in GCK pregnancies. There was an increased percentage of miscarriages in GCK pregnancies highlighting the importance of a diagnosis of GCK-MODY in women prior to conception and the necessity for preconception care.

Fasting plasma glucose as initial screening for diabetes and prediabetes in irish adults: The Diabetes Mellitus and Vascular health initiative (DMVhi).

OBJECTIVE: Type 2 diabetes has a long pre clinical asymptomatic phase. Early detection may delay or arrest disease progression. The Diabetes Mellitus and Vascular health initiative (DMVhi) was initiated as a prospective longitudinal cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes, diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75 years. RESEARCH DESIGN AND METHODS: Members of the largest Irish private health insurance provider aged 45 to 75 years were invited to participate in the study. EXCLUSION CRITERIA: already diagnosed with diabetes or taking oral hypoglycaemic agents. Participants completed a detailed medical questionnaire, had weight, height, waist and hip circumference and blood pressure measured. Fasting blood samples were taken for fasting plasma glucose (FPG). Those with FPG in the impaired fasting glucose (IFG) range had a 75gm oral glucose tolerance test performed. RESULTS: 122,531 subjects were invited to participate. 29,144 (24%) completed the study. The prevalence of undiagnosed diabetes was 1.8%, of impaired fasting glucose (IFG) was 7.1% and of impaired glucose tolerance (IGT) was 2.9%. Dysglycaemia increased among those aged 45-54, 55-64 and 65-75 years in both males (10.6%, 18.5%, 21.7% respectively) and females (4.3%, 8.6%, 10.9% respectively). Undiagnosed T2D, IFG and IGT were all associated with gender, age, blood pressure, BMI, abdominal obesity, family history of diabetes and triglyceride levels. Using FPG as initial screening may underestimate the prevalence of T2D in the study population. CONCLUSIONS: This study is the largest screening study for diabetes and prediabetes in the Irish population. Follow up of this cohort will provide data on progression to diabetes and on cardiovascular outcomes.

The role of preanalytical glycolysis in the diagnosis of gestational diabetes mellitus in obese women.

OBJECTIVE: The objective of this prospective observational study was to determine whether the preanalytical management of maternal plasma glucose samples had a significant effect on glucose measurements in obese pregnant women. STUDY DESIGN: Based on the accurate calculation of body mass index in the first trimester, obese women were recruited at their convenience. In 1 cohort, fasting glucose level was measured in early pregnancy; in the other cohort, an oral glucose tolerance test was performed at 24-28 weeks' gestation. Paired samples were taken from all women in both cohorts. The first sample was transferred to the laboratory in iced water for immediate analysis (fast-tracked analysis). The second sample was not placed on ice and transferred according to established hospital practices (hospital-tracked analysis). RESULTS: Of the 24 women who had a fasting glucose test in early pregnancy, the result was abnormal (≥5.1 mmol/L) in 7 women (29%) with hospital-tracked analysis compared with 16 women (67%) with fast-tracked analysis (P < .01). The mean phlebotomy-analysis interval was 119 minutes for the hospital-tracked samples compared with 23 minutes for the fast-tracked samples (P < .001). Of the 24 women who had a glucose tolerance test, the fasting glucose level was abnormal in 4 women (17%) after hospital-tracked analysis compared with 13 women (54%) after fast-tracked analysis (P < .01). The hospital-tracked phlebotomy-analysis interval for the fasting sample of the 24-28 week oral glucose tolerance test cohort was 166 minutes compared with 25 minutes for the fast-tracked samples (P < .001). CONCLUSION: Unless maternal fasting glucose samples are transported on ice and analyzed immediately in the laboratory, gestational diabetes mellitus will be underdiagnosed in obese women.

Hypertension presenting early in pregnancy.

Paraganglioma in pregnancy is an exceedingly rare and potentially life-threatening diagnosis. It is important that the clinicians consider secondary causes when women present with hypertension in early pregnancy.

Insulin therapy for the treatment of type 1 diabetes during pregnancy.

Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient.

Serial fetal abdominal circumference measurements in predicting normal birth weight in gestational diabetes mellitus.

OBJECTIVES: To construct a clinical management matrix using serial fetal abdominal circumference measurements (ACMs) that will predict normal birth weight in pregnancies complicated by gestational diabetes (GDM) and reduce unnecessary ultrasound examination in women with GDM. STUDY DESIGN: Retrospective cohort study of 144 women with GDM in a specialist obstetric-diabetes clinic. Women with GDM who delivered singleton infants were identified from a clinical register. Regression analysis was used to identify associations between serial ACMs, maternal parameters and normal birth weight (birth weight between the 10th and 90th percentiles). Predictive clinical models were designed with the aim of identifying normal birth weight infants with the lowest number of fetal ultrasound scans. RESULTS: Compared to mothers of large-for-gestational-age (LGA) infants, mothers of normal weight infants had lower fasting glucose measurements at diagnosis (5.9 mmol/l±1.0 vs. 6.6 mmol/l±0.7, p<0.05), lower maternal weight at delivery (90 kg±17 vs. 96 kg±17, p<0.05), and a lower rate of prior LGA infants (31% vs. 60%, p<0.05). Maternal weight and a history of prior LGA delivery were identified as useful predictors of fetal birth weight in predictive models. Serial ACMs below the 50th, 75th and 90th percentiles could predict normal birth weight with 100%, 97% and 96% positive predictive value respectively when used in these risk factor based models. Two measurements sufficed in low-risk pregnancies. CONCLUSION: Serial ACMs can predict normal birth weight in GDM.

Screening for metabolic syndrome in long-termp sychiatric illness: Audit of patients receiving depot antipsychotic medication at a psychiatry clinic

Background and Objectives: Metabolic syndrome (visceral obesity, dyslipidaemia, hyperglycaemia, hypertension) is a substantial public health problem, especially amongst individuals receiving antipsychotic medication. Methods: We studied routine screening practices for metabolic syndrome amongst psychiatry outpatients receiving injected depot anti-psychotic medication at a clinic in Dublin, Ireland. Results: Our initial audit (n = 64) demonstrated variable levels of documentation of criteria for metabolic syndrome in outpatient files; e.g. weight was recorded in 1.6% of files, serum high density lipoprotein in 12.5%. As our intervention, we introduced a screening check-list comprising risk factors and criteria for metabolic syndrome, based on the definition of the International Diabetes Federation. Re-audit (n = 54) demonstrated significantly improved levels of documentation; e.g. weight was recorded in 61.1% of files. Notwithstanding these improvements, only 11 (20.4%) of 54 patient files examined in the re-audit, contained sufficient information to determine whether or not the patient fulfilled criteria for metabolic syndrome; of these, 3 patients (27.3%) fulfilled criteria for metabolic syndrome. There was, however, significant additional morbidity in relation to individual criteria (waist circumference, serum triglyceride level, systolic blood pressure and serum fasting glucose).Conclusions: We recommend enhanced attention be paid to metabolic morbidity in this patient group(AU)

Caesarean section and macrosomia increase transient tachypnoea of the newborn in type 1 diabetes pregnancies.

We determined whether transient tachypnoea of the newborn (TTN) is more common in macrosomic versus normal weight infants and in those delivered by caesarean section versus vaginally, in a retrospective cohort analysis of 212 type 1 diabetes pregnancies. Caesarean section and macrosomia were both associated with higher TTN rates.

Teenage pregnancy in type 1 diabetes mellitus.

Younger maternal age at delivery has been linked to adverse reproductive outcomes. Pregnancy complicated by type 1 diabetes mellitus (T1DM) is also associated with adverse pregnancy outcomes. Optimising diabetic glycaemic control prior to pregnancy is known to reduce the rate of congenital abnormalities and improve pregnancy outcomes. Teenage pregnancies are not usually planned and little data exist on teenage pregnancy complicated by T1DM. We sought to identify the glycemic control achieved in teenage pregnancy with T1DM and to clarify if there is an associated increase in adverse pregnancy outcomes compared to those seen in older women with T1DM. We compared outcomes in 18 teenagers (TG) with 582 older women with T1DM (CON) from 1995-2007. TG booked to the combined diabetes-obstetrical service at a median gestational age of 11 weeks (range 6-22) compared to 7 weeks in CON (range 4-40, p < 0.02). Glycaemic was worse in TG compared to CON at 13, 26 and 35 weeks gestation, despite higher insulin doses. First trimester miscarriage rate did not differ between groups. Major congenital anomaly rate was 6.2% (1/16) compared to 3.2% in CON. This preliminary study has demonstrated that pregnant teenage women with T1DM book later to specialised care and have worse glycaemic control in pregnancy compared to older women with T1DM. This group also appear to be more insulin resistant than older women in early pregnancy. Our data would suggest that teenagers with type 1 diabetes mellitus may constitute a high-risk group for adverse pregnancy outcomes.

Effect of pregestational diabetes mellitus on fetal cardiac function and structure.

OBJECTIVE: Fetuses of diabetic pregnancy experience cardiomyopathy, the intracardiac cause of which is understood poorly. The aim of this study was to assess the interrelation between cardiac functional and structural changes in fetuses of mothers with pregestational diabetes mellitus. STUDY DESIGN: Twenty-six mothers with pregestational diabetes mellitus were recruited prospectively to have a fetal echocardiogram at 13, 20, and 36 weeks of gestation to assess cardiac function and structure. For comparison, 30 healthy control subjects were recruited at each gestational age. RESULTS: In the first trimester, there was evidence of poorer fetal cardiac diastolic function among the diabetic cohort (lower left early/atrial ratio, longer isovolumetric relaxation time and higher left myocardial performance index; P < .05). In the third trimester, the fetal interventricular septum and the right ventricular free wall were thicker in the diabetic cohort (P < .05). CONCLUSION: In fetuses of pregestational diabetic pregnancy, sonographic evidence of altered cardiac function is evident before ultrasound evidence of cardiac structural changes. This suggests that altered cardiac function may precede cardiac structural changes in fetuses of pregestational diabetic pregnancy.

Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women.

OBJECTIVE: To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects (n = 322) who were pregnant or planning pregnancy were randomized to IAsp or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C < or =8% at confirmation of pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C <6.5%. Outcomes assessed included risk of major maternal hypoglycemia, A1C, plasma glucose profiles, and maternal safety outcomes. RESULTS: Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI, respectively (relative risk 0.720 [95% CI 0.36-1.46]). Risk of major/major nocturnal hypoglycemia was 52% (RR 0.48 [0.20-1.143]; P = NS) lower with IAsp compared with HI. A1C was comparable with human insulin in second (IAsp-HI -0.04 [-0.18 to 0.11]) and third (-0.08 [-0.23 to 0.06]) trimesters. A total of 80% of subjects achieved an A1C < or =6.5%. At the end of first and third trimesters, average postprandial plasma glucose increments were significantly lower with IAsp than HI (P = 0.003 and P = 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P = 0.044 and P = 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments. CONCLUSIONS: IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia.

Achieving better outcomes in pregnancies complicated by type 1 and type 2 diabetes mellitus.

BACKGROUND: Pregnancy in type 1 and type 2 diabetes mellitus (DM) is associated with an increased rate of adverse outcomes for both mother and fetus. OBJECTIVE: This article reviews the data available on achieving better outcomes in pregnancies complicated by DM. METHODS: Background materials for this article were gathered based on a PubMed search of English-language articles (up to and including August 2007) using the search terms diabetes mellitus, pregnancy, glycemic control, mortality, and morbidity. This review article was based on a presentation given at a satellite symposium entitled "Realising the Value of Modern Insulins: Reaching Further with Rapid-Acting Insulin Analogues" that was convened during the XIXth World Diabetes Congress, December 3, 2006, in Cape Town, South Africa. RESULTS: There is clear evidence that optimized metabolic control, from preconception through pregnancy, can reduce the risk of maternal and fetal complications in women with DM. The risk of fetal congenital abnormalities in pregnant women with DM is intricately related to the level of glycemic control in early pregnancy; thus, strict metabolic targets as close to normal glycosylated hemoglobin (HbA1c) (ie, 4.0%-6.0%) as possible are recommended. However, these HbA1c and postprandial plasma glucose targets are challenging for the physician and the patient. The rapid-acting insulin analogues, insulin aspart and insulin lispro, may be useful because they can reduce postprandial hyperglycemia without increasing the risk for hypoglycemia and even provide a small improvement in HbA1c compared with regular human insulin. In a recent, prospective, randomized controlled study of pregnant women with type 1 DM (N=322), maternal hypoglycemia, metabolic control, and tolerability, including perinatal outcomes, were compared between those randomized to mealtime insulin aspart or human insulin. The results from this study suggest that insulin aspart is at least as effective and well tolerated as human insulin in basal-bolus therapy with neutral protamine Hagedorn insulin. Overall, 80% of study participants in both groups achieved HbA1c levels