Project ID CM-HD2024_61


Co Supervisor 1A Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Women & Children’s HealthWebsite

Co Supervisor 1B Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Twin Research & Genetic EpidemiologyWebsite

Untangling pathophysiological pathways to hyperglycaemia in pregnancy

Gestational diabetes (GDM) defined by new onset hyperglycaemia in pregnancy is associated with short and long-term maternal and offspring morbidity, affects ~14% of pregnancies worldwide and prevalence is increasing. The yes/no diagnosis at 24-28 weeks’ gestation suggests homogeneity, reinforcing the dogma of a single pathological entity. This is discordant with the observed clinical diversity, including variation in time of onset, hyperglycaemic patterns and treatment response. Better understanding of the biological pathways that distinguish GDM subgroups will facilitate a personalised approach to management.

This project, using data collected as part of the MRC-funded UNiCoRN Study (Understanding the causes of Hyperglycaemia in Pregnancy; MR/W003740/1) will explore pathophysiologically distinct subgroups leading to hyperglycaemia in a cohort comprising women of White and South Asian descent. Disease subtypes will be elucidated through integration of maternal and clinical data and targeted hormonal profiles captured at oral glucose tolerance tests in early and mid-pregnancy. A breadth of training spanning biostatistical analysis and precision medicine will be offered. This study will lay the foundation for targeted therapy for GDM leading to improved outcomes for mother and child.

Principal Objectives will include:
1. Identification of factors (clinical/biochemical) that distinguish between subtypes of GDM at 24-28 weeks’ gestation to facilitate targeted management.
2. Identification of factors (clinical/biochemical) in early pregnancy associated with GDM subtypes to facilitate earlier targeted intervention.
3. Exploration of distributions of GDM subtypes across White and South Asian groups.

Overarching objectives:
1. Years 1 and 2: specific PhD training in biostatistics, epidemiology and other targeted data courses. Training and involvement in UNiCoRN study procedures. Towards the middle of year 2 which should coincide with completion of recruitment, collation, cleaning, and understanding of the breadth of data prior to analyses.
2. Year 3: Hypothesis-driven specific analyses as detailed in principal objectives, preparation of manuscripts and thesis completion.

Representative Publications

Rational Testing: Screening and Diagnosis of Gestational Diabetes. White SL, Ayman G, Bakhai C, Hillier TA, Magee LA. BMJ, 2023. doi: Towards precision medicine in gestational diabetes: pathophysiology and glycemic patterns in pregnant women with obesity. White SL, Koulman A, Ozanne SE, Furse S, Poston L, Meek CL. J Clin Endocrinol Metab, 2023. Metabolic profiling of gestational diabetes in obese women during pregnancy. White SL, Pasupathy D, Sattar N, Nelson SM, Lawlor DA, Briley AL, Seed PT, Welsh P, Poston L; UPBEAT Consortium. Diabetologia, 2017
Cherny SS, Williams FMK, Livshits G. Genetic and environmental correlational structure among metabolic syndrome endophenotypes. Annals of Human Genetics. 2022;86(5):225-236. doi: /10.1111/ahg.12465 CHARGE Inflammation Working Group. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis, and inflammation: discovering causal pathways. Human Molecular Genetics. 2022. doi: org/10.1093/hmg/ddac061. Williams FMK, Elgaeva EE, Freidin MB, Zaytseva OO, Aulchenko YS, Tsepilov YA et al. Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study. European Spine Journal. 2022 Jul;31(7):1906-1915. doi: 10.1007/s00586-022-07263-2