Combination immunotherapy has a greater risk of development of endocrinopathy compared to anti-PD-1 monotherapy. Regular biochemical profiling of patients, particularly within the first twelve weeks, results in early detection of endocrinopathy to minimise morbidity.

Background & Aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically-and genetically-activated cell proliferation, and HCC.

Aims To investigate whether long-term glycaemic variability (GV) is associated with vascular complication development in Type 2 diabetes Methods In a post-hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of HbA1c and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by Chi square and ANOVA. Prospective associations between baseline to two-year GV and subsequent vascular and mortality outcomes were analysed using landmark logistic and Cox proportional hazards regression. Results Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 (95% CI 1.01–1.03) p<0.01; HR 1.01 (95% CI 1.00–1.01) p<0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 (95% CI 1.00–1.04); HR 1.01 (95% CI 1.00–1.02), both p<0.05). HbA1c CV associated with increased stroke (HR 1.03 (95% CI 1.01–1.06) p<0.01). Glucose CV associated with increased coronary events (HR 1.01 (95% CI 1.00–1.02) p<0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 (95% CI 1.02–1.06); HR 1.01 (95% CI 1.01–1.02), both p<0.001) and non-cardiovascular mortality (HR 1.05 (95% CI (1.03–1.07); HR 1.02 (95% CI 1.01–1.03), both p<0.001). HbA1c CV associated with coronary mortality (HR 1.04 (95% CI 1.01–1.07) p<0.05). Conclusions Long-term GV was associated with increased risk of vascular outcomes in Type 2 diabetes.

Identification and subsequent treatment of GDM in twin pregnancy demonstrates a similar risk of adverse perinatal outcomes compared with non-GDM twin pregnancies.

No abstract

Diabetes Care 2017;40:e98-e100 | https://doi.org/10.2337/dc17-0626Fetal exposure to hyperglycemia is a major determinant of large-for-gestationalage (LGA; birth weight .90th centile for gender) neonates (1), yet targets for glycemic control beyond the first trimester in type 1 diabetes (T1D) pregnancy remain controversial. As HbA 1c represents a summary measure of glycemic control, it might not adequately reflect acute glucose fluctuations or glycemic variability (GV) that contributes to excess fetal growth. Moreover, neonates born to women who attain HbA 1c ,6% (42 mmol/mol) in the third trimester of pregnancy have an LGA prevalence of 25% (2), with associated adverse perinatal outcomes (3). In contrast to HbA 1c , continuous glucose monitoring (CGM) allows precise observation of GV. Several studies have demonstrated an association between higher GV and increased birth weight (1,4,5). The capability of GV compared with HbA 1c to identify women likely to have LGA neonates is, however, unclear. We evaluated the association between various measures of GV, HbA 1c , and LGA neonates in T1D pregnancy.Twenty-one pregnant women with T1D were recruited over a 2-year period, and measurements of HbA 1c and GV (EasyGV, University of Oxford, Oxford, U.K.) using CGM (Medtronic, Macquarie Park, New South Wales, Australia) were carried out at three time points: 14-18, 24-28, and 32-36 weeks' gestation. The study was approved by the local ethics committee (Northern Sydney Local Health District Human Research Ethics Committee), and all participants gave written informed consent.The mean 6 SD gestational age at delivery was 37.5 6 1.4 weeks, and birth weight was 3,454 6 576 g, with eight neonates born LGA. HbA 1c at each time point was 6.1 6 0.9%, 6.0 6 0.8%, and 6.2 6 1.0%, respectively. The LGA group had significantly higher mean glucose and GV indices than the non-LGA group at 24-28 weeks' gestation ( Fig. 1A-D) and higher HbA 1c at each time point (Fig. 1E).Linear regression demonstrated a significant association between birth weight centile and each of the glycemic measures at 24-28 weeks of gestation. Because the GV indices demonstrated significant colinearity, we included the J-index alone in subsequent analyses, as it was most strongly correlated with birth weight centile (r 5 0.853; P , 0.0001). Using univariate linear modeling, J-index at 24-28 weeks maintained a significant independent association with birth weight centile (r 2 5 0.229; P , 0.05), whereas HbA 1c did not (r 2 5 0.008; P 5 0.713). The combination of J-index and HbA 1c at this time point resulted in a greater association with birth weight centile (r 2 5 0.477; P , 0.01), with mean values of 31.7% and 5.95%, respectively. Furthermore, using cutoffs of HbA 1c .6% and J-index .30 identified all neonates that were born LGA (receiver operating characteristic curve analysis, data not shown).Despite attaining close to recommended HbA 1c target levels for T1D in pregnancy (HbA 1c #6%), our cohort of women demonstrated an ;40% incidence of LGA neonates, which conc...

The factors that mediate disease progression in both ARLD and NAFLD have been shown to involve a complex interplay between environmental risk factors (eg sustained high levels of alcohol consumption or a sedentary lifestyle and poor diet, features of the metabolic syndrome) and genetic risk factors. To date, this interplay and all the factors involved are incompletely understood.

ObjectiveTo determine if continuous subcutaneous insulin infusion (CSII) therapy is associated with lower glycated haemoglobin (HbA1c) variability (long-term glycaemic variability; GV) relative to multiple daily injection (MDI) treatment in adults with type 1 diabetes mellitus (T1DM).DesignRetrospective audit.Setting and participantsClinic records from 506 adults with T1DM from two tertiary Australian hospitals.Outcome measuresLong-term GV was assessed by HbA1c SD and coefficient of variation (CV) in adults on established MDI or CSII therapy, and in a subset changing from MDI to CSII.ResultsAdults (n=506, (164 CSII), 50% women, mean±SD age 38.0±15.3 years, 17.0±13.7 years diabetes, mean HbA1c 7.8%±1.2% (62±13 mmol/mol) on CSII, 8.0%±1.5% (64±16 mmol/mol) on MDI) were followed for 4.1±3.6 years. CSII use was associated with lower GV (HbA1c SD: CSII vs MDI 0.5%±0.41% (6±6 mmol/mol) vs 0.7%±0.7% (9±8 mmol/mol)) and CV: CSII vs MDI 6.7%±4.6% (10±10 mmol/mol) vs 9.3%±7.3% (14±13 mmol/mol), both p<0.001. Fifty-six adults (73% female, age 36±13 years, 16±13 years diabetes, HbA1c 7.8%±0.8% (62±9 mmol/mol)) transitioned from MDI to CSII. Mean HbA1c fell by 0.4%. GV from 1 year post-CSII commencement decreased significantly, HbA1c SD pre-CSII versus post-CSII 0.7%±0.5% (8±5 mmol/mol) vs 0.4%±0.4% (5±4 mmol/mol); p<0.001, and HbA1c CV 9.2%±5.5% (13±8 mmol/mol) vs 6.1%±3.9% (9±5 mmol/mol); p<0.001.ConclusionsIn clinical practice with T1DM adults relative to MDI, CSII therapy is associated with lower HbA1c GV.