Clinical trial NCT03785951: Impact of Whey and Leucine on Glycaemia in Adults Without Diabetes
Official title: Impact of Whey and Leucine on Glycaemia in Adults Without Diabetes But With Moderately Raised HbA1c
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pre Diabetes
Keywords: HbA1c
whey
postprandial glycaemia
cardiometabolic
vascular
leucine
branched chain amino acids (BCAA)
glucose control
Milk protein
Lead sponsor: University of Reading
Sponsor class: OTHER
Collaborators: name: Barnham Benevolent Foundation
name: Jason and Daphne Mermikides Charitable Trust
First posted: 2018-12-24
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, randomised, controlled, 3-way, cross-over study
Primary purpose: PREVENTION

Brief summary: Higher than average blood sugar (glucose) levels are linked to an increased risk of developing type 2 diabetes. As such, there is interest in identifying dietary factors that could lower blood glucose to help reduce the number of people with this disease. Findings from some human studies indicate that dairy products, especially a milk protein (whey), may help the control of blood glucose levels. However, there is a need for further studies to confirm these findings in individuals without diabetes but with higher than average blood glucose levels.

Detailed description: In the UK, more than 700 people are diagnosed with type 2 diabetes each day. Higher than average (raised) fasting blood sugar (glucose) is a characteristic of those at risk of developing this disease and as a result there is significant interest in dietary factors that could reduce levels of blood glucose, lowering the frequency of type 2 diabetes in the population. Existing scientific evidence suggests an important role of dairy products and especially of whey protein in the control of blood glucose levels. However, there is a need for further studies to confirm these findings in individuals without diabetes but with higher than average blood glucose levels.

Milk contains high quality proteins, of which 80% are caseins and 20% are whey proteins. Whey proteins are a rich source of branched-chain amino acids (such as leucine) which are thought to play an important role in regulating blood glucose control and other aspects of cardiovascular disease development in both healthy and type 2 diabetic subjects. However, very few studies in non-diabetic subjects with moderately raised HbA1c, characteristic of long-term poor glucose control, have been performed to investigate how whey protein affects blood glucose levels in the body especially when consumed over the longer term in the daily diet. Furthermore, data are limited on whether the leucine content of protein plays an important role in controlling blood glucose levels.

Study aims The main aims of this study is to investigate in adults without diabetes but with moderately raised HbA1c (a long- term marker of blood glucose control) whether a protein obtained from milk and dairy products (whey) has a beneficial effect on fasting and day-long blood glucose and insulin levels compared with a plant based protein (such as wheat). The researchers will also determine if leucine, a particular amino acid (building blocks of protein) found in higher levels in whey protein plays an important role in controlling blood glucose levels.

A secondary aim will determine whether the protein interventions influence risk markers for developing heart disease and diabetes including the level of blood lipids, hormones regulating blood sugar levels and blood vessel health.

This study will test the hypothesis that the incorporation of whey protein (total protein dose 50 g/d) in the habitual diet for 8 weeks will result in an improvement in fasting and day-long blood glucose and insulin levels, and other risk markers of heart disease and diabetes compared with wheat protein (total protein dose 50 g/d), and that the addition of leucine to wheat (to match the content found in whey protein) will improve blood glucose control.

Study design This study will be a long term, double-blind, randomised, controlled, three-way, cross-over study, in which the participants will receive the protein supplements (in random order) for 8 weeks each, with a 4 week wash-out period between the different protein treatments. At the beginning and end of each protein intervention, a fasting blood sample will be collected to determine the longer term effects of the assigned protein supplement on fasting glycaemic control, insulin sensitivity, endothelial function and other cardio-metabolic risk markers, as well as non-invasive measures of blood vessel health. At the beginning of each intervention period, a subset of participants will also undergo a day-long test meal investigation to determine the short-term (postprandial) effects of the protein interventions on the study outcome measures in response to standard sequential test meals containing the assigned protein interventions.

Eligibility criteria: Inclusion Criteria:

* BMI 20-35 kg/m2
* HbA1c (5.7 - 6.5%) or (38.8 - 47.5 mmol/mol)
* Fasting glucose 5.5-6.9 mmol/l
* Fasting total cholesterol \<7.5mmol/l
* Fasting triacylglycerol \<4.0 mmol/l
* Not having a milk, gluten or wheat allergy or lactose intolerability
* Not having diabetes (HbA1c \< 47 mmol/mol) or \< 6.5%
* Not suffering from cardiovascular, renal, gastrointestinal, respiratory, endocrine or liver disease
* Not having hypertension
* Not diagnosed with cancer
* Not having surgery in the previous 6 months
* Not consuming more than the recommended intake of alcohol (\>14 unit/wk)
* Not being a blood donor 3 months prior to or during the study.
* Not taking extra protein powder supplements in the previous 2 months
* Not anaemic (Haemoglobin ≥115 g/l for women and ≥ 130 g/l for men)
* Not taking medication for raised blood lipids, high blood pressure or for inflammatory conditions.

Exclusion Criteria:

• Females who are breast-feeding, may be pregnant, or if of child-bearing potential and are not using effective contraceptive precautions

Primary outcomes:
measure: Change in fasting and day long glucose levels
timeFrame: Before and after each 8 week intervention.
measure: Change in fasting and day long insulin levels
timeFrame: Before and after each 8 week intervention.
Secondary outcomes:
measure: Change in vascular reactivity measured by Laser Doppler Imaging with iontophoresis
timeFrame: Before and after each 8 week intervention.
measure: Change in the total and HDL-cholesterol
timeFrame: Before and after each 8 week intervention
measure: Change in fructosamine
timeFrame: Before and after each 8 week intervention
measure: Change in C-reactive protein
timeFrame: Before and after each 8 week intervention
measure: Change in pulse wave analysis
timeFrame: Before and after each 8 week intervention
measure: Change in blood pressure
timeFrame: Before and after each 8 week intervention
measure: Change in cellular adhesion molecule
timeFrame: Before and after each 8 week intervention
measure: Change in selectins
timeFrame: Before the start of the intervention
measure: Change in beta-hydroxy butyrate
timeFrame: Before and after each 8 week intervention
measure: Change in insulin sensitivity
timeFrame: Before and after each 8 week intervention
measure: Change in non-esterified fatty acids
timeFrame: Before and after each 8 week intervention
measure: Measurement of height
timeFrame: Before the start of the intervention
measure: Change in body weight
timeFrame: Before and after each 8 week intervention
measure: Change in body mass index
timeFrame: Before and after each 8 week intervention
measure: Change in body composition
timeFrame: Before and after each 8 week intervention
Other outcomes:
measure: Metabonomics
timeFrame: Before and after each 8 week intervention
Locations:
city: Reading
country: United Kingdom
facility: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading
state: Berkshire
Study officials:
affiliation: University of Reading
name: Julie Lovegrove, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pal S, Ellis V, Dhaliwal S. Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals. Br J Nutr. 2010 Sep;104(5):716-23. doi: 10.1017/S0007114510000991. Epub 2010 Apr 9.
citation: Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr. 2004 Nov;80(5):1246-53. doi: 10.1093/ajcn/80.5.1246.