Our study aims to identify unique Metabotypes among individuals with overweight at risk of T2DM and assess their response to a 1-year precision dietary macronutrient modulation. The objective is to provide proof-of-concept that this approach…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Extensive characterization will be done before, during, and after the
intervention. Primary outcome measure is whole-body insulin sensitivity
(Matsuda index) assessed by means of a 7-point oral glucose tolerance test
(OGTT).
Secondary outcome
Secondary outcomes include glycaemic variability, mean glucose levels, fasting
lipid profiles, body composition, blood pressure, gene and protein expression
of adipose tissue, microbial composition and functionality, metabolomics,
physical activity, adherence to dietary recommendations, (mental) well-being,
and quality of life.
Background summary
Worldwide, the prevalence of obesity, type 2 diabetes mellitus (T2DM),
cardiometabolic diseases as well as an impaired mental health and depression
has grown dramatically over the past decades. Currently employed general
population-based guidelines for healthy nutrition have only proven effective in
reducing type 2 diabetes (T2DM) incidence in individuals with prediabetes by up
to 50%. Notwithstanding, a significant 30% of participants within these
programs do not respond or adhere to such interventions. Recent studies
indicate that precision nutrition interventions, tailored to metabolic
phenotypes (metabotypes) with distinct T2DM aetiologies, yield superior
outcomes in blood glucose control, and potentially enhance intervention
adherence.
We hypothesize that the use of a precision nutrition intervention strategy,
based on Metabotypes identified by an unsupervised clustering (machine
learning) of prespecified accurate prediabetic state features/variables, will
improve blood glucose homeostasis and cardiometabolic risk status, as well as
adherence to the intervention and (mental) well-being compared to
population-based dietary guidelines. The present project will contribute to
targeted and efficient precision-based dietary strategies for individuals at
increased risk of T2DM.
Study objective
Our study aims to identify unique Metabotypes among individuals with overweight
at risk of T2DM and assess their response to a 1-year precision dietary
macronutrient modulation. The objective is to provide proof-of-concept that
this approach improves glucose homeostasis, dietary adherence, and psychosocial
well-being compared to population-based dietary guidelines.
Study design
Two-centre dietary intervention study with a double-blind, randomized
controlled parallel design, based on participants* Metabotype and hypothesized
optimal diet. Participants* Metabotype and intervention arm will be blinded to
the participants and researchers. Metabotypes were identified through
hierarchical clustering of Principal Components (HCPC) using baseline data from
The Maastricht Study (participant demographics, body composition, glucose- and
insulin metabolism), whereafter clusters were cross-validated in independent
cohorts. Based on a combination of post-hoc analyses of dietary intervention
trials and literature, for these metabotypes the optimal dietary macronutrient
composition was determined.
Intervention
Following screening, baseline measurements, and determination of Metabotype,
participants will be randomly assigned, using minimization, to either the
Precision Nutrition (PN) group or the Control (CN) group. The PN group will
receive a hypothesized optimal diet for their specific Metabotype, while the
control group will be randomly assigned one of the diets optimized for a
different Metabotype of the same sex. All participants will follow their
assigned diets for 12 months, with each diet conforming to the Dutch healthy
dietary guidelines (Gezondheidsraad, 2015).
Study burden and risks
Burdens that participants may experience include the time they need to invest
in the study and the dietary restrictions during the 12-month intervention
period. The total time investment during the both Characterization Week (CW)
measurements will be around 8,75 hours, divided over 2 university visits and 13
days of intermediate assessments at home. Additionally, the participants will
be asked to report to the University at months 1, 3, 6 and 9 and record dietary
intake at home on three non-consecutive days before the visit. During the visit
at 6 months, classification measurements (OGTT and DXA) will be performed
again. In total, these intermediate visits will require time investment of
approximately 13 additional total hours. The total study period, including
screening and intervention will be approximately 13 months.
The following burdens or risks may be associated with participation:
• Wearing the continuous glucose monitor (CGM) and physical activity (PA)
monitor may be considered a burden. However, previous experience has shown that
most participants do not experience this as a burden. Current CGMs no longer
require regular calibration by finger-prick and capillary blood glucose
measurement, reducing any potential experienced burden on participants.
• The collection of faeces and urine may be considered a burden. However, based
on previous experience, this procedure is quite feasible.
• Throughout the study, questionnaires will be completed and food intake will
be record-ed periodically by means of a mobile app (Traqq) during daily life,
which requires an extra time investment.
• During the test days, blood will be collected via a venous catheter.
Venapunctures can occasionally cause a local hematoma or bruise. Some
participants in previous studies reported pain during a venapuncture.
• Adipose tissue (AT) biopsies will be taken twice (pre-, post-intervention and
at 6-months in MUMC+ only). An adipose tissue biopsy may cause local hematoma.
Com-pressing the biopsy site for approximately 10 minutes will reduce the risk
of developing hematoma. Discomfort during the procedure itself is minimized due
to the use of local anaesthetics, although participants may experience pressure
during the introduction of the needle. The incision will leave a small scar (~3
mm). To promote good wound heal-ing, the incision will be sealed with
steristrips and a waterproof band-aid.
• No risks are known about the OGTT. This measurement is routinely applied in
human metabolic research, and SOPs are available in the database of our
department.
• The total radiation dose participants will be exposed to during the three DXA
scans is <30 µSv. Since the average yearly radiation dose per person in the
Netherlands is ap-proximately 2.9 mSv, the amount of radiation exposure during
DXA scans is negligible.
• Dietary products provided during the intervention are widely used and freely
available to consumers. Both the composition of the diets and individual food
products will not cause discomfort for the participants and are in line with
the Dutch healthy dietary guidelines (Gezondheidsraad 2015).
Aside from receiving information about their health status, participants are
provided with specific foods that may be beneficial and may support adherence
to the intervention diets or general guidelines. Furthermore, since the
prevalence of overweight and cardio-metabolic disorders is continuing to rise,
study outcomes could provide future health benefits for the general public. In
addition, the diets that the participants will follow are advantageous to
overall health.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
Men and women with overweight and obesity (age 40-75 years, BMI 25-40 kg/m2),
without (Pre-)diagnosis of type 1 or type 2 diabetes mellitus. Stable body
weight for at least 3 months (+/-3 kg).
Exclusion criteria
- (Pre-)diagnosis of type 1 or type 2 diabetes mellitus (i.e., FPG >= 7,0
mmol/L) and HbA1c >= 6,5% (48 mmol/mol)
- Renal or hepatic malfunctioning (pre-diagnosis or determined based on ALAT
and creatinine values)
- Gastrointestinal diseases or abdominal surgery (allowed i.e.: appendectomy,
cholecystectomy)
- Food allergies, intolerances (including gluten/lactose intolerance) and/or
eating disorders interfering with the study
- Cardiovascular diseases (e.g., heart failure) or cancer (e.g., non-invasive
skin cancer allowed)
- High systolic blood pressure (untreated >160/100 mmHg, drug-regulated >140/90
mmHg)
- Diseases affecting glucose and/or lipid metabolism (e.g., pheochromocytoma,
Cushing*s syndrome, acromegaly)
- Diseases with a life expectation shorter than 5 years
- Major mental disorders
- Drug treated thyroid diseases (well substituted hypothyroidism is allowed
inclusion)
- Other physical/mental conditions that may interfere with study outcomes
- Medication known to interfere with study outcomes (e.g., PPAR-α or PPAR-γ
agonists (fibrates), sulfonylureas, biguanides, α-glucosidase inhibitors,
thiazolidinediones, repaglinide, nateglinide, insulin, and chronic use of
NSAIDs)
- Use of certain anticoagulants other than acetylsalicylic acid
- Use of antidepressants (stable use >= 3 months prior to and during study
allowed)
- Use of statins (stable use >= 3 months prior to and during study allowed)
- Chronic corticosteroids treatment (*7 consecutive days of treatment)
- Use of antibiotics within 3 months prior to the study
- Participation in regular sports activities (moderate-to-vigorous physical
exercise >4 hours per week)
- Having a restricted dietary pattern interfering with the study diets (e.g.,
vegetarian, vegan, Atkins diet and/or other special diets)
- Plans to lose more than 5% body weight
- Abuse of alcohol (alcohol consumption >14 units/week) and/or drugs (cannabis
included)
- Not willing to limit alcohol consumption to 7 drinks per week
- Regular smoking (including use of e-cigarettes)
- Use of strong vitamins or other dietary supplements (e.g., pre- or
probiotics) expected to interfere with the study outcomes
- Metabotype classification is not possible
- Pregnant or lactating women, or women who are planning to become pregnant
- Inability to comply with the study diet
- Participation in possibly interfering studies within the last 3 months
- Inability to understand study information and/or communicate with staff
- Unwillingness to be randomized or sign informed consent
- Unwillingness to save data for 15 years
Design
Recruitment
Medical products/devices used
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In other registers
| Register | ID |
|---|---|
| CCMO | NL87817.068.24 |