An Exploration of the Use of the Postload-Fasting Gap as a Tool to Predict the Risk of Developing Diabetes

Abstract

Diabetes and vascular complications pose a significant burden on public health, yet current diagnostic frameworks rely mainly on static glycaemic thresholds, such as fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG), and glycated haemoglobin (HbA1c), which may not capture early metabolic disturbances. This thesis explores the clinical relevance and predictive value of the postload–fasting gap, defined as the difference between 2hPG and FPG, in identifying early metabolic disturbances and vascular risk in Chinese adults.
Firstly, a comprehensive narrative review is presented of the organ-specific mechanisms underlying the postload–fasting gap, summarising how hepatic and peripheral glucose handling contribute to both positive and negative gap values. The review positions the postload–fasting gap as an integrative biomarker reflecting multi-organ coordination in glucose metabolism.
Secondly, a cross-sectional study using baseline data from the SENSIBLE study found that low post load (FPG ≥ 2hPG) was observed in 26.04% of the natural population, and low post load was found to be related to younger age, male, lower BMI, lower blood pressure, higher HDL cholesterol levels and lower triglyceride levels.
Thirdly, a prospective cohort study using the SENSIBLE-cohort study at baseline and two follow-up re-visits showed that participants with high post load (FPG < 2hPG) showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal from prediabetes to normal glucose tolerance (NGT) was lower.
Fourthly, further dose–response analyses showed a monotonic increase in the risks of diabetes, prediabetes, and disease progression with larger positive values of the postload–fasting gap, whereas negative values were associated with relatively lower risks. In contrast, the probability of disease reversal decreased steadily as the postload-fasting gap increased, indicating that greater postload–fasting differences reflect progressively impaired glucose regulation.
Fifthly, the prognostic value of the postload–fasting gap was assessed for vascular complications. A prospective analysis based on data from the first and second re-visits of the SENSIBLE-cohort suggested that individuals with either highly negative or highly positive values of the postload–fasting gap had increased risks of developing vascular complications, including both microvascular and macrovascular events. Notably, these associations remained robust across glycaemic strata, including individuals with NGT.
In conclusion, the postload–fasting gap is a physiologically meaningful, dynamic indicator of early glucose dysregulation. Its inclusion in routine oral glucose tolerance test interpretation may enhance risk stratification and support more personalised prevention strategies for diabetes and vascular complications.

Date of Award	9 Mar 2026
Original language	English
Awarding Institution	Liverpool School of Tropical Medicine
Supervisor	Anupam Garrib (Supervisor), Shabbar Jaffar (Supervisor) & Duolao Wang (Supervisor)