title: The impact of dairy proteins on fasting and postprandial glycaemic control
Creators: name: Chatzidiakou, Giannoula
Publisher: name: University of Reading
Year: 2024

description: Type 2 diabetes (T2D) characterised by abnormal glycaemic control is a major public health 
concern worldwide. As a result, there is significant interest in dietary components, that could 
help regulate blood glucose concentrations, lowering the prevalence of this disease in the 
population. Available epidemiological evidence has suggested that there is a neutral or even 
a protective inverse association of milk and dairy product consumption with T2D. These 
beneficial effects of dairy foods have been largely attributed to whey protein (WP); a dairy 
component rich in branched chain amino acids (BCAAs) which have been proposed to play a 
key role in the maintenance of glycaemic control. However, few studies have been conducted 
to investigate how WP controls blood glucose levels, especially when consumed over the 
longer-term in the diet. To address the lack of knowledge, the literature review (Chapter 1)
included randomised control trials (RCTs) evaluating the chronic and acute effects of WP
intake on glycaemic control as well as elucidating the underlying mechanisms of action.
Findings suggested a more favourable benefit of acute WP intake on markers of postprandial 
glycaemic control in T2D patients, with inconsistent effects in normoglycaemic individuals. 
Although there were a limited number of studies determining the chronic effects of dietary WP
on measures of glucose control, beneficial effects were reported on fasting insulin but not on 
glucose levels in normoglycaemic volunteers whereas in T2D patients, favourable reductions
were evident on fasting HbA1c, a long-term marker of glycaemic control. L-Leucine, a key 
BCAA in WP, alone or in combination with other BCAAs, emerged as a potential modulator of 
the postprandial insulinotropic effect mediated via effects of incretin gut hormones, but 
evidence was limited. 
Epidemiological evidence generally supported a favourable relationship between dairy 
product consumption and reduced risk of T2D (Guo et al., 2019). However few studies have 
been examined the role of total dairy and different dairy foods on glycaemic control. To explore 
the association between consumption of total dairy and different dairy products and changes 
in markers of glucose control a cross-sectional and longitudinal analysis was conducted using 
data from the Caerphilly Prospective Cohort study (CAPs) (Chapter 2). Cross-sectional 
analysis in the 1,350 men at baseline revealed no associations between total dairy, milk, 
cheese, cream, or butter with markers of glycaemic control [plasma glucose, insulin, and 
indices of insulin resistance (IR)], with a similar relationship evident after a five year follow up. 
Our findings from this cohort study are in accordance with previous epidemiological studies 
and support the neutral effect of dairy products on glycaemic control and T2D risk.
The long-term consumption of milk proteins in mildly hypertensive people improved 
their vascular reactivity, biomarkers of endothelial function while WP resulted in a decrease of 
24-h ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the acute 
within chronic Whey2Go study. Additionally, the acute ingestion of WP reduced the 
postprandial BP and improved arterial stiffness while Ca-caseinate improved lipid metabolism. 
To provide further insights into the impact of milk proteins on glycaemic control and the role 
of gut hormones as part of the mechanisms and mainly due to limited and unclear evidence 
available from chronic intervention studies a secondary analysis of the acute within chronic 
Whey2Go study was performed (Chapter 3). Although chronic consumption of 56 g of whey 
protein isolate (WPI), Ca-caseinate and maltodextrin intervention had limited impact on fasting 
glucose, insulin, glucagon, ghrelin, glucagon like peptide-1 (GLP-1), glucose-dependent 
insulinotropic polypeptide (GIP) and C-peptide after 8 weeks, differences were evident during 
the postprandial phase at the beginning of each intervention period. Our findings suggested a 
greater impact of the milk proteins on postprandial glucose control, potentially mediated by 
GLP-1. To further explore the role of WP and leucine on postprandial glycaemic control, the 
randomised controlled Whey2Glo study determined the acute effects of sequential high-fat 
meals containing 50 g (2 x 25 g) of WPI, partially hydrolysed wheat protein (PHWP), and 
PHWP supplemented with leucine to match the content in WPI (Chapter 4). Addition of leucine 
to PHWP was associated with a greater postprandial insulinotropic response compared with 
PHWP but the effects on postprandial glycaemia were limited between the protein 
interventions. The divergent effects of WPI and PHWP plus leucine on postprandial C-peptide, 
GIP and glucagon responses also suggested that WPI and PHWP plus leucine may regulate 
glycaemic control by different mechanisms, which is worthy of further investigation.
Collectively, findings from this thesis suggest that acute, but not chronic, intake of milk proteins 
has a beneficial effect on glycaemic control and plasma hormone responses. Moreover, the 
addition of leucine to PHWP was associated with a greater postprandial insulinotropic effect 
and supports the hypothesis that this BCAA may represent one of the bioactive amino acids 
for glucose control in WPI. Further sufficiently powered studies should address the impact of 
milk proteins on risk factors for developing T2D and examine the mechanisms underlying the 
role of leucine on glycaemic control.