The role of dietary lipids in glucose homeostasis
File(s)
Author(s)
Siddiqui, Mohsin Sohail
Type
Thesis
Abstract
Type 2 Diabetes (T2DM) is a pressing global health issue with high morbidity, mortality and socioeconomic burden. Despite pharmacologic advances, the drug accessibility remains limited especially in lower income countries. Dietary
interventions, such as the Mediterranean diet, have been emerging as promising complementary therapy due to their cardiovascular benefits.
This thesis explores the utility of extra virgin olive oil (EVOO), a major component of Mediterranean diet, in glucose regulation through the action of the gut peptide, Neurotensin (NT). The first part of the thesis examined the relationship between fasting NT levels and metabolic parameters. Fasting NT concentrations were higher in individuals with T2DM and in females. However, no significant link was identified with microvascular complications of diabetes. A systematic review explored the acute effects of dietary fat on postprandial glucose in healthy adults without diabetes. The fat addition showed modest, albeit nonsignificant, blunting of glycaemia without substantial changes in insulin concentration. A second pooled analysis investigating the substitution of saturated fatty acids with monounsaturated fatty acid, in a single fat containing meal, did not demonstrate glucose lowering postprandially.
The second part of the thesis examined the dose response effect of EVOO administration on NT secretion. These pilot studies demonstrated that EVOO (10–30 mL) stimulates NT secretion, peaking at 60–90 minutes, with no additional benefit at higher dose. A subsequent cross over trial comparing EVOO to coconut oil preloads found no significant differences in glucose or insulin responses, though a trend toward lower postprandial glucose was noted. NT elevation did not differ between oils, suggesting NT-independent mechanisms or its rapid degradation. This work contributes to growing understanding of dietary fat’s role in glucose regulation highlighting its potential role in non-pharmacologic management of T2DM. Future studies are required to clarify NT’s glucoregulatory actions through its more stable precursors.
interventions, such as the Mediterranean diet, have been emerging as promising complementary therapy due to their cardiovascular benefits.
This thesis explores the utility of extra virgin olive oil (EVOO), a major component of Mediterranean diet, in glucose regulation through the action of the gut peptide, Neurotensin (NT). The first part of the thesis examined the relationship between fasting NT levels and metabolic parameters. Fasting NT concentrations were higher in individuals with T2DM and in females. However, no significant link was identified with microvascular complications of diabetes. A systematic review explored the acute effects of dietary fat on postprandial glucose in healthy adults without diabetes. The fat addition showed modest, albeit nonsignificant, blunting of glycaemia without substantial changes in insulin concentration. A second pooled analysis investigating the substitution of saturated fatty acids with monounsaturated fatty acid, in a single fat containing meal, did not demonstrate glucose lowering postprandially.
The second part of the thesis examined the dose response effect of EVOO administration on NT secretion. These pilot studies demonstrated that EVOO (10–30 mL) stimulates NT secretion, peaking at 60–90 minutes, with no additional benefit at higher dose. A subsequent cross over trial comparing EVOO to coconut oil preloads found no significant differences in glucose or insulin responses, though a trend toward lower postprandial glucose was noted. NT elevation did not differ between oils, suggesting NT-independent mechanisms or its rapid degradation. This work contributes to growing understanding of dietary fat’s role in glucose regulation highlighting its potential role in non-pharmacologic management of T2DM. Future studies are required to clarify NT’s glucoregulatory actions through its more stable precursors.
Version
Open Access
Date Issued
2025-07-30
Date Awarded
2026-03-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Murphy, Kevin
Sam, Amir
Lessan, Nader
Sponsor
Imperial College London
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)