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Impact of Whey and Leucine on Glycaemia in Adults Without Diabetes

Not Applicable
Conditions
Pre Diabetes
Interventions
Dietary Supplement: Whey Protein Isolate
Dietary Supplement: Wheat Protein
Dietary Supplement: Wheat Protein with Leucine
Registration Number
NCT03785951
Lead Sponsor
University of Reading
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Whey Protein IsolateWheat ProteinSubjects are asked to supplement their habitual diet with 56 g of whey protein isolate a day for 8 weeks
Wheat ProteinWheat Protein with LeucineSubjects are asked to supplement their habitual diet with 56 g of wheat protein a day for 8 weeks
Whey Protein IsolateWhey Protein IsolateSubjects are asked to supplement their habitual diet with 56 g of whey protein isolate a day for 8 weeks
Whey Protein IsolateWheat Protein with LeucineSubjects are asked to supplement their habitual diet with 56 g of whey protein isolate a day for 8 weeks
Wheat ProteinWhey Protein IsolateSubjects are asked to supplement their habitual diet with 56 g of wheat protein a day for 8 weeks
Wheat ProteinWheat ProteinSubjects are asked to supplement their habitual diet with 56 g of wheat protein a day for 8 weeks
Wheat protein with leucineWheat Protein with LeucineSubjects are asked to supplement their habitual diet with 56 g of wheat protein with leucine a day for 8 weeks
Wheat protein with leucineWheat ProteinSubjects are asked to supplement their habitual diet with 56 g of wheat protein with leucine a day for 8 weeks
Wheat protein with leucineWhey Protein IsolateSubjects are asked to supplement their habitual diet with 56 g of wheat protein with leucine a day for 8 weeks
Primary Outcome Measures
NameTimeMethod
Change in fasting and day long glucose levelsBefore and after each 8 week intervention.

Blood glucose levels will be measured using a clinical chemistry analyser

Change in fasting and day long insulin levelsBefore and after each 8 week intervention.

Blood insulin levels will be measured using ELISA

Secondary Outcome Measures
NameTimeMethod
Change in the total and HDL-cholesterolBefore and after each 8 week intervention

Fasting total cholesterol and HDL-C will be measured using a clinical chemistry analyser. LDL-C will be calculated using the Friedewald formula

Change in fructosamineBefore and after each 8 week intervention

Fructosamine will be measured using a clinical chemistry analyser

Change in vascular reactivity measured by Laser Doppler Imaging with iontophoresisBefore and after each 8 week intervention.

Fasting and day long measurement of vascular reactivity in the microcirculation.

Change in non-esterified fatty acidsBefore and after each 8 week intervention

Non-esterified fatty acids will be measured using a clinical chemistry analyser

Change in body compositionBefore and after each 8 week intervention

Body composition will be measured using bioelectrical impedance.

Change in pulse wave analysisBefore and after each 8 week intervention

Pulse wave analysis will be measured using the Mobil-O-Graph device

Change in insulin sensitivityBefore and after each 8 week intervention

Glucose and insulin levels will be used to estimate insulin sensitivity using the Homeostatic model assessment calculation

Change in body weightBefore and after each 8 week intervention

Body weight will be measured using the Tanita scale

Change in C-reactive proteinBefore and after each 8 week intervention

C-reactive protein

Change in cellular adhesion moleculeBefore and after each 8 week intervention

VCAM and ICAM will be measured by Luminex, ICAM, P-selectin and E-selectin

Change in beta-hydroxy butyrateBefore and after each 8 week intervention

Beta-hydroxy butyrate will be measured using a clinical chemistry analyser as a marker of ketone bodies

Measurement of heightBefore the start of the intervention

Height will be measured using a stadiometer

Change in body mass indexBefore and after each 8 week intervention

Body mass index will be calculated from body weight and height measurement

Change in blood pressureBefore and after each 8 week intervention

Systolic blood pressure, diastolic blood pressure and pulse pressure

Change in selectinsBefore the start of the intervention

P-selectin and E-selectin will be measured using Luminex

Trial Locations

Locations (1)

Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading

🇬🇧

Reading, Berkshire, United Kingdom

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