Brendan Kinsley

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.

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.

Insulin therapy for the treatment of type 1 diabetes during pregnancy

Abstract 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.

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.

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

Background and Objectives: Metabolic syndrome (visceral obesity, dys- lipidaemia, hyperglycaemia, hypertension) is a substantial public health problem, espe- cially amongst individuals receiving antipsychotic medication. Methods: We studied routine screening practices for metabolic syndrome amongst psy- chiatry 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 crite- ria 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 defini- tion 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. Notwith- standing 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.

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.

Neonatal heart rate variability in type 1 diabetic pregnancy

Introduction In adult diabetic patients, abnormalities in heart rate variability can predict mortality post myocardial infarction. Fetuses of diabetic mothers are at increased risk of unexplained death in utero and it is possible that there may be an association with underlying alterations in fetal autonomic function. The objective of this study is to determine if neonatal autonomic function differs between normal and pregestational type 1 diabetic pregnancy. Methods Thirty-eight patients with pregestational type 1 diabetes mellitus and 26 healthy controls were prospectively recruited. All patients had neonatal heart rate variability assessed using Powerlab (AdiInstruments) and cord blood sampling for arterial and venous pH and glucose was performed. Results Significant differences were found between the two cohorts. In the diabetic cohort, there was increased overall power, increased low frequency (LF), decreased high frequency (HF) with an increased LF:HF ratio, (p values 0.016, 0.016 and 0.042, respectively) reflecting sympathetic over activity. These differences were independent of gestational age and birthweight centile. There were also significant associations between heart rate variability and fetal academia (p=0.01) and maternal and fetal glycaemic control (p<0.05 and p=0.019, respectively). Conclusion This study shows significant evidence of autonomic dysfunction in neonates of type 1 diabetic mothers. This may be related to the effect of prolonged fetal exposure to the hyperglycaemic milieu of diabetic pregnancy. Autonomic dysfunction may have a role in unexplained fetal death as it is influenced by acidosis and hyperglycaemia; features associated with fetal death in pregestational diabetic pregnancy.