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.