The heritability of beta cell function parameters in a mixed meal test design

Aims/hypothesis: We estimated the heritability of individual differences in beta cell function after a mixed meal test designed to assess a wide range of classical and model-derived beta cell function parameters. Methods: A total of 183 healthy participants (77 men), recruited from the Netherlands Twin Register, took part in a 4 h protocol, which included a mixed meal test. Participants were Dutch twin pairs and their siblings, aged 20 to 49 years. All members within a family were of the same sex. Insulin sensitivity, insulinogenic index, insulin response and postprandial glycaemia were assessed, as well as model-derived parameters of beta cell function, in particular beta cell glucose sensitivity and insulin secretion rates. Genetic modelling provided the heritability of all traits. Multivariate genetic analyses were performed to test for overlap in the genetic factors influencing beta cell function, waist circumference and insulin sensitivity. Results: Significant heritabilities were found for insulinogenic index (63%), beta cell glucose sensitivity (50%), insulin secretion during the first 2 h postprandial (42-47%) and postprandial glycaemia (43-52%). Genetic factors influencing beta cell glucose sensitivity and insulin secretion during the first 30 postprandial min showed only negligible overlap with the genetic factors that influence waist circumference and insulin sensitivity. Conclusions/interpretation: The highest heritability for postprandial beta cell function was found for the insulinogenic index, but the most specific indices of heritability of beta cell function appeared to be beta cell glucose sensitivity and the insulin secretion rate during the first 30 min after a mixed meal. © The Author(s) 2011

High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses

Organisms in experimental research

Rachel A. Ankeny and Sabina Leonell

Cardiovascular risk factors in those born preterm - systematic review and meta-analysis

Emerging evidence demonstrates a link between preterm birth (PTB) and later life cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to compare conventional CVD risk factors between those born preterm and at term. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. The review protocol is registered in PROSPERO (CRD42018095005). CVD risk factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index, lipid profile, blood glucose, and fasting insulin among those born preterm (<37 weeks' gestation) were compared with those born at term (≥37 weeks' gestation). Subgroup analyses based on gender, age, gestational at birth (<32 weeks' gestation and <28 weeks' gestation), and PTB associated with small for gestational age or average for gestational age were also performed. Fifty-six studies provided data on 308,987 individuals. Being born preterm was associated with 3.26 mmHg (95% confidence interval [CI] 2.08 to 4.44) higher mean SBP and 1.32 mmHg (95% CI: 0.61 to 2.04) higher mean DBP compared to being born at term. Subgroup analyses demonstrated that SBP was higher among (a) preterm compared to term groups from early adolescence until adulthood; (b) females born preterm but not among males born preterm compared to term controls; and (c) those born at <32 weeks or <28 weeks compared to term. Our meta-analyses demonstrate higher SBP and DBP among those born preterm compared to term. The difference in SBP is evident from early adolescence until adulthood.Prabha H. Andraweera, Bradley Condon, Gemma Collett, Stefania Gentilcore, Stefania Gentilcore, Zohra S. Lass