Menopause is associated with postprandial metabolism, metabolic health and lifestyle: The ZOE PREDICT study

Background The menopause transition is associated with unfavourable alterations in health. However, postprandial metabolic changes and their mediating factors are poorly understood.Methods The PREDICT 1 UK cohort (n=1002; pre-n=366, peri-n=55, and post-menopausal females n=206) assessed phenotypic characteristics, anthropometric, diet and gut microbiome data, and fasting and postprandial (0-6 h) cardiometabolic blood measurements, including continuous glucose monitoring (CGM) data. Differences between menopausal groups were assessed in the cohort and in an age-matched subgroup, adjusting for age, BMI, menopausal hormone therapy (MHT) use, and smoking status.Findings Post-menopausal females had higher fasting blood measures (glucose, HbA1c and inflammation (GlycA), 6%, 5% and 4% respectively), sugar intakes (12%) and poorer sleep (12%) compared with pre-menopausal females (p<0.05 for all). Postprandial metabolic responses for glucose2hiauc and insulin2hiauc were higher (42% and 4% respectively) and CGM measures (glycaemic variability and time in range) were unfavourable post-versus pre -meno-pause (p<0.05 for all). In age-matched subgroups (n=150), postprandial glucose responses remained higher post -menopause (peak0-2h 4%). MHT was associated with favourable visceral fat, fasting (glucose and insulin) and post-prandial (triglyceride6hiauc) measures. Mediation analysis showed that associations between menopause and meta-bolic health indicators (visceral fat, GlycA360mins and glycaemia (peak0-2h)) were in part mediated by diet and gut bacterial species.Interpretation Findings from this large scale, in-depth nutrition metabolic study of menopause, support the impor-tance of monitoring risk factors for type-2 diabetes and cardiovascular disease in mid-life to older women to reduce morbidity and mortality associated with oestrogen decline.