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The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an Australia-wide observational pregnancy-birth cohort of children at genetic risk on account of a first-degree relative with type 1 diabetes (1). 1511 participants were recruited from all Australian States and Territories from 2013-2019 with 1473 live-born infants in follow-up. The standard protocol involves 3-monthly face-to-face visits from pregnancy until the child is 2 years of age, then 6-monthly visits. Study staff across nine centres in five States collect biospecimens (blood, urine, stool, swabs) and administer lifestyle and dietary questionnaires. Approximately 10% of the cohort are engaged in a Regional Participant Program (2) that requires self-collection of sample types except for venepuncture performed at local pathology services.

With no current randomized trials, we explored the impact of tight compared with standard treatment targets on pregnancy outcomes in gestational diabetes mellitus (GDM).This cohort study of singleton births ≥ 28 weeks' gestation was conducted at two major Australian maternity services (2009-2013). Standardized maternal, neonatal and birth outcomes were examined using routine healthcare data and compared for women with GDM at Service One (n = 2885) and Service Two (n = 1887). Services applied different treatment targets: Service One (standard targets, reference group) fasting5.5 mmol/l, 2-h postprandial7.0 mmol/l; Service Two (tight targets) fasting5.0 mmol/l, 2-h postprandial6.7 mmol/l. Multivariable regression with propensity score adjustment was used to examine associations between targets and outcomes.GDM prevalence and insulin use were 7.9% and 31% at Service One, and 5.7% and 46% at Service Two. There were no differences in primary outcomes: birthweight90th centile [adjusted odds ratio (OR) 1.06, 95% confidence interval (CI) 0.87-1.30] and10th centile (OR 0.84, 95% CI 0.70-1.01), or secondary outcomes gestational hypertension, pre-eclampsia, shoulder dystocia or a perinatal composite. Service Two with tight targets had increased induction of labour (OR 3.63, 95% CI 3.17-4.16), elective Caesarean section (OR 1.75, 95% CI 1.37-2.23) and Apgar scores7 at 5 min (OR 1.54, 95% CI 1.05-2.25), decreased hypoglycaemia (OR 0.76, 95% CI 0.61-0.94]), jaundice (OR 0.47, 95% CI 0.35-0.63) and respiratory distress (OR 0.68, 95% CI 0.47-0.98).Tight GDM treatment targets were associated with greater insulin use and no difference in primary birthweight outcomes. The service with tight targets had higher obstetric intervention, lower rates of reported hypoglycaemia, jaundice, respiratory distress and lower Apgar scores. High-quality interventional data are required before tight treatment targets can be implemented.

Scope: In experimental studies, moderate to high concentrations of sCD14 (serum cluster of differentiation 14 protein) prevent lipopolysaccharide (LPS)-induced systemic inflammation, while low concentrations may promote inflammation. Given that metabolic endotoxemia is thought to initiate high-fat diet-induced insulin resistance, we explored the association between sCD14 concentrations and insulin sensitivity in humans. Methods and results: Healthy non-obese (n = 12, BMI 26 ± 5y), obese (n = 11, BMI 33.45 ± 3.2) and morbidly obese participants (n = 38, BMI 45 ± 7) underwent measurement of body composition (dual energy X-ray absorptiometry) and a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity (M value). Circulating sCD14 concentrations were measured by ELISA. Non-obese participants had lower circulating sCD14 concentrations compared to obese (p = 0.03). Circulating sCD14 concentrations were positively associated with percent body fat, waist circumference and white blood cell count and negatively associated with insulin sensitivity. In contrast, circulating sCD14 were positively associated with insulin sensitivity in morbidly obese participants. In regression analysis, insulin sensitivity (r = 0.52, p = 0.004) and fasting triglycerides (r = 0.49, p = 0.005) contributed independently to circulating sCD14 variance after controlling for age, sex and BMI in these morbidly obese subjects. Conclusion: These findings suggest that circulating sCD14 concentrations, through its compensatory (in non-obese subjects) or buffering role (in morbidly obese subjects), could exert an important role in modulating insulin sensitivity.

Diabet. Med. 28, 54–60 (2011) Abstract Aims To comprehensively characterize large artery biomechanical properties and examine their relationship to cardiac function in patients with Type 2 diabetes mellitus (DM). Methods Fifty-five individuals with Type 2 DM were compared with 66 age- and sex-matched healthy control subjects. Arterial biomechanical properties were assessed by systemic arterial compliance (SAC; two-element Windkessel model), carotid–femoral pulse wave velocity (PWVc-f), femoral–dorsalis pedis pulse wave velocity (PWVf-d) and carotid augmentation index. Cardiac structure and function were assessed by echocardiography. Results Individuals with Type 2 DM had lower SAC and higher PWVc-f when compared with the healthy population. The PWVc-f was significantly lower than the PWVf-d in control individuals, but this difference was not evident in individuals with Type 2 DM due to higher PWVc-f. Augmentation index was similar in both groups, but the time to the first systolic inflection (time to reflection) was shorter in the individuals with Type 2 DM. The individuals with Type 2 DM had a greater prevalence of diastolic abnormalities when compared with the control group. Arterial stiffness indices, including SAC and pulse pressure, correlated with left ventricular filling pressure (defined as peak velocity during early diastolic filling divided by the velocity of movement of the mitral valve annulus in early diastole; r= −0.33 and 0.36 respectively. Conclusions Patients with Type 2 DM on standard medication showed preferential stiffening of the large central arteries. However, carotid augmentation index was not different between the two groups and is therefore not a reliable indicator of large artery stiffening in this patient group. Diastolic dysfunction, present in a significant proportion of this population with Type 2 DM, was closely associated with arterial stiffening, suggesting a common aetiology.