Menopause Is Associated With Postprandial Metabolism, Metabolic Health and Lifestyle: The ZOE PREDICT Study

Abstract

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 (0-6h) 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 glucose_2hiauc and insulin_2hiauc were higher (42 and 4% respectively) and CGM measures (glycaemic variability and time in range) were unfavourable post- versus pre-menopause (p<0·05 for all). In age-matched subgroups (n =150), postprandial glucose responses remained higher post-menopause (peak_0-2h 4%). MHT was associated with favourable visceral fat, fasting (glucose and insulin) and postprandial (triglyceride_6hiauc ) measures. Mediation analysis showed that associations between menopause and metabolic health indicators (visceral fat, GlycA_360mins and glycemia (peak_0-2h )) 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 importance 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.

Funding Information: This work was supported by ZOE Ltd and TwinsUK which is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.

Declaration of Interests: TDS and JW are co-founders of ZOE Ltd (ZOE). TDS, FA, NS, PWF, LMD, JMO, AMV and SEB are consultants to ZOE. IL, KK, and RD are employed by ZOE. Other authors have no conflict of interest to declare. The study sponsors (ZOE) contributed as part of the Scientific Advisory Board in the study design and collection.

Ethics Approval Statement: Ethical approval for the study was obtained in the United Kingdom from the Research Ethics Committee and Integrated Research Application System (IRAS 236407), and in the United States from the institutional review board (Partners Healthcare IRB 2018P002078). The trial was registered on ClinicalTrials.gov (registration number: NCT03479866) as part of the registration for the PREDICT program of research, which also includes two other study protocol cohorts. The trial was run in accordance with the Declaration of Helsinki and Good Clinical Practice.

Keywords: Menopause, postprandial metabolic response