The primary objective of the proposed study is to examine and understand the impact of long-term almond consumption on chronic glucose metabolism in subjects with prediabetes (either impaired glucose tolerance (IGT) and/or impaired fasting glucose (…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is glucose infusion rate (GIR) determined during a
hyperinsulinemic euglycemic clamp, as measure for whole body insulin
sensitivity.
Secondary outcome
* To investigate if improved chronic glucose metabolism in subjects with
prediabetes after long-term almond consumption translates into improved
peripheral and brain vascular function, and enhanced cognitive performance.
* To examine to what extent improved chronic glucose metabolism in subjects
with prediabetes after long-term almond consumption can be explained by
(combined) effects of lowered hepatic lipid accumulation and inflammation,
skeletal muscle characteristics, visceral and subcutaneous fat accumulation,
pancreatic function or fecal microbiota composition.
Background summary
Almond consumption is associated with ameliorations in various factors
associated with cardiovascular disease (CVD) risk such as hyperglycemia,
hyperlipidemia, and hypertension. Most of the intervention studies described
were well-controlled, but relatively short. Therefore the question is whether
these effects are sustained over longer time. An additional question is how the
protective effects on glycemic control and CVD risk can be explained
mechanistically. Therefore in the current study we will combine a long-term
intervention study with a panel of state of the art techniques to understand
the potential mechanisms underlying the observed health effects.
Study objective
The primary objective of the proposed study is to examine and understand the
impact of long-term almond consumption on chronic glucose metabolism in
subjects with prediabetes (either impaired glucose tolerance (IGT) and/or
impaired fasting glucose (IFG), as measured by whole body insulin sensitivity.
Secondary objectives are to investigate if improved chronic glucose metabolism
in subjects with prediabetes after long-term almond consumption translates into
improved peripheral and brain vascular function, and enhanced cognitive
performance. In addition, we will address to what extent improved chronic
glucose metabolism in subjects with prediabetes after long-term almond
consumption can be explained by (combined) effects of lowered hepatic lipid
accumulation and inflammation, skeletal muscle characteristics, visceral and
subcutaneous fat accumulation, pancreatic function or fecal microbiota
composition.
Study design
The proposed study will be a 12 months randomized, well-controlled trial with a
cross-over design. Two experimental periods of five months will be separated by
a two months wash out period.
Intervention
During the intervention period of 5 months, subjects will receive daily 50 gr
almonds, but not in the 2 months washout and 5 months control periods.
Study burden and risks
Subjects will be screened to determine eligibility during two visits of 150 and
15 minutes. During these screening visits, anthropometric measurements will be
performed and blood pressure will be determined. In addition, a venous blood
sample (9.0 mL) will be drawn and IGT and IFG status will be determined via an
OGTT test (4.0 ml blood sampled two hours after drinking a standardized 250 mL
glucose solution). During the study there will be 6 separate blood sampling
moments and 4 test days (2x postprandial test and 2x clamp test). No direct
health benefit for the study participants is expected. Investigational products
are safe, i.e. the almonds and all ingredients to prepare the mixed meals for
the postprandial test are commercially available and approved for human
consumption. There are no side effects for the almonds as well as the mixed
meals. In total during the entire study 496 mL blood will be sampled (two
screenings of each 13 mL, six times 15 mL fasting, 2 postprandial test days of
105 mL each, and two clamp test days of 85 mL each). Some study subjects may
report pain during venipuncture. Insertion of the cannula can cause some
discomfort and possible a hematoma or bruise. Some subjects may also report
pain during the insertion of the cannula. Sampling adipose and skeletal muscle
tissue biopsies is performed under local anaesthesia, a hematoma can occur due
to invasive method for taking the fat biopsy, and muscle pain can occur due to
invasive method for taking muscle tissue biopsy. In principle, all measurements
are routine in our metabolic research unit (MRUM) and are not expected to lead
to physical side effects. Time investment for the participants is approximately
32 hours, excluding travel time.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
- Aged between 40-75 years
- Men and women
- BMI between 25-40 kg/m2 (overweight and obese)
- Being classified as having prediabetes, either having impaired glucose
tolerance (IGT) and/or having impaired fasting glucose (IFG). IGT is defined
according the criteria of the WHO and American Diabetes Association (ADA) as
two-hour glucose concentrations of 7.8 to 11.0 mmol/l (140 to 199 mg per dL)
during the 75-g oral glucose tolerance test. IFG is defined as having a fasting
plasma glucose between 6.1 and 7.0 mmol/l (110 to 125 mg per dL) and a two-hour
glucose concentration below 7.8 mmol/l (140 mg per dL).
- Serum total cholesterol < 8.0 mmol/L (further testing is recommended for
excessive hyperlipidemia [serum total cholesterol * 8.0 mmol/L] according to
the Standard for cardiovascular risk management of the Dutch general
practitioners community [NHG])
- Serum triacylglycerol < 4.52 mmol/L
- No current smoker
- No diabetic patients
- No familial hypercholesterolemia
- No abuse of drugs
- Not more than 4 alcoholic consumption per day with a maximum of 21 per
week??
- Stable body weight (weight gain or loss < 3 kg in the past three months)
- No use of medication known to treat blood pressure, lipid or glucose
metabolism
- No use of an investigational product within another biomedical intervention
trial within the previous 1-month
- No severe medical conditions that might interfere with the study, such as
epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive
pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and
rheumatoid arthritis
- No active cardiovascular disease like congestive heart failure or
cardiovascular event, such as an acute myocardial infarction or cerebrovascular
accident
- Willingness to give up being a blood donor from 8 weeks before the start of
the study, during the study and for 4 weeks after completion of the study
- No difficult venipuncture as evidenced during the screening visit
- Willing to comply to study protocol during study
- Informed consent signed
Exclusion criteria
- Allergy or intolerance to almonds
- Serum total cholesterol * 8.0 mmol/L
- Serum triacylglycerol * 4.52 mmol/L
- Current smoker, or smoking cessation <12 months
- Diabetic patients
- Familial hypercholesterolemia
- Abuse of drugs
- More than 4 alcoholic consumptions per day or 21 per week
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Use medication known to treat blood pressure, lipid or glucose metabolism
- Use of an investigational product within another biomedical intervention
trial within the previous 1-month
- Severe medical conditions that might interfere with the study, such as
epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive
pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and
rheumatoid arthritis
- Active cardiovascular disease like congestive heart failure or
cardiovascular event, such as an acute myocardial infarction or cerebrovascular
accident
- Not willing to give up being a blood donor from 8 weeks before the start of
the study, during the study or for 4 weeks after completion of the study
- Not or difficult to venipuncture as evidenced during the screening visit
- Use of over-the-counter and prescribed medication or supplements, which may
interfere with study measurements to be judged by the principal investigator;
- Use of oral antibiotics in 40 days or less prior to the start of the study;
- Blood donation in the past 3 months before the start of the study
- Not willing to comply to study protocol during study or sign informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03419702 |
| CCMO | NL61425.068.17 |