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AIMS: Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations. METHODS: Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion. RESULTS: Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised β' 0.393 (0.289-0.498), p = 1.3 × 10-12; n = 306), but not with glucose concentrations (p = 0.3). The association with insulin was still evident when adjusting for BMI (β' 0.271 (0.180-0.362), p = 1.1 × 10-8; n = 297). Likewise, at 120 min the OGTT GLP-1 concentrations were associated with plasma insulin concentrations (β' 0.216 (0.100-0.331), p = 2.7 × 10-4; n = 306) even after adjusting for BMI (β' 0.178 (0.061-0.294), p = 2.9 × 10-3; n = 296), but not with glucose (p = 0.9). GIP concentrations were not associated with insulin or glucose concentrations at either time point (all p > 0.2). In pregnancy plasma GLP-1, but not GIP, concentrations appear to be predictive of circulating insulin concentrations, independently of associations with BMIs. CONCLUSIONS: These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology.

Aims Precision medicine has revolutionized our understanding of type 1 diabetes and neonatal diabetes but has yet to improve insight into gestational diabetes mellitus (GDM), the most common obstetric complication and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1 hour, 2 hours) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles. Methods 867 pregnant women with obesity (body mass index ≥ 30 kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks’ gestation (75 g oral glucose tolerance test OGTT; World Health Organization criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analyzed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterized by homeostatic model assessment 2b and 2s, respectively. Results In women who developed GDM (n = 241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycemia had comparable insulin secretion and sensitivity to euglycemic women, potentially indicative of a novel mechanistic pathway. Conclusions Patterns of glycemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycemia reflects a different mechanistic pathway for targeted management.

The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA1c) measures in first (n = 221), second (n = 197), and third (n = 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR)

Objective: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of beta-cell regeneration in type 1 diabetes pregnancy. Research Design & Methods: C-peptide was measured on maternal serum samples from 127 participants (12, 24, 34 weeks) and cord blood during the continuous glucose monitoring in type 1 diabetes pregnancy trial (CONCEPTT). C-peptide was measured using a highly sensitive direct and solid-phase competitive electrochemiluminescent immunoassay. Results: Three discrete patterns of maternal C-peptide trajectory were identified: Pattern 1 undetectable throughout pregnancy, n=74 (58%, maternal C-peptide Conclusion: First maternal C-peptide appearance at 34 weeks was associated with mid-trimester hyperglycemia, elevated cord blood C-peptide and high rates of neonatal complications. This suggests transfer of C-peptide from fetal to maternal serum and is inconsistent with pregnancy-related beta-cell regeneration.

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres (ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. Trial registration: This trial is registered with ClinicalTrials.gov. number NCT01788527. Trial registered 11/2/2013.

Objective: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. Methods: 157 women from the CGM in pregnant women with type 1 diabetes trial (CONCEPTT) were included in this pre-specified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5 anhydroglucitol, fructosamine and glycated albumin) were compared at approximately 12, 24 and 34 weeks gestation using logistic regression and ROC curves to predict pregnancy complications (pre-eclampsia, preterm delivery, large-for-gestational-age, neonatal hypoglycemia, admission to neonatal intensive care unit). Results: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks gestation. More outcomes were associated with CGM metrics during the 1st trimester and with laboratory markers (area under ROC generally 140 mg/dl; >7.8 mmol/l) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. Conclusions: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared to widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

Wernicke’s encephalopathy is caused by thiamine deficiency and has a range of presenting features, including gait disturbance, altered cognitive state, nystagmus and other eye movement disorders. In the past, Wernicke’s encephalopathy was described almost exclusively in the alcohol-dependent population. However, in current times, Wernicke’s encephalopathy is also well recognized in many other patient groups, including patients following bariatric surgery, gastrointestinal surgery, cancer and pancreatitis. Early recognition of Wernicke’s encephalopathy is vital, as prompt treatment can restore cognitive or ocular function and can prevent permanent disability. Unfortunately, Wernicke’s encephalopathy is often undiagnosed – presumably because it is relatively uncommon and has a variable clinical presentation. Clinical biochemists have a unique role in advising clinicians about potential nutritional or metabolic causes of unexplained neurological symptoms and to prompt consideration of thiamine deficiency as a potential cause in high-risk patient groups. The aim of this review is to summarize the clinical features, diagnosis and treatment of Wernicke’s encephalopathy and to highlight some non-traditional causes, such as after bariatric surgery.

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