Clinical trial NCT05990205: Effect of the SCL16A11 Risk Haplotype on Treatments to Prevent Type 2 Diabetes
Official title: Effect of the Genetic Variants Typical of the Mestizo Population That Confer Risk of Having Metabolic Diseases on the Response to Common Treatments (Diet, Physical Activity, Metformin, Exercise).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: PreDiabetes
Keywords: PreDiabetes
Metformin
Precision nutrition
SLC16A11
Mexican Mestizos
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this randomized clinical trial is to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D in Mexican mestizos with prediabetes. The main question\[s\] it aims to answer are:

* Evaluate the effect of the risk haplotype on weigth loss \>3%
* Evualuate the differences in lipid profiles and glycemic parameters (fasting glucose, HbA1c).

Participants will be randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day).

Researchers will compare carriers and non carriers of the risk haplotype of SLC16A11 to see if there are diferent treatment responses.

Detailed description: Objectives: Dietary modification and/or metformin remain the most cost-effective treatment to prevent type 2 diabetes (T2D). Yet, there is an important variation in receiving the benefit among individuals. A haplotype in SLC16A11 is associated with decreased insulin action and risk for T2D in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D.

Methods: We recrute individuals with at least one prediabetes criteria according to the American Diabetes Association with a body mass index (BMI) between 25 and 45 kg/m2. Participants are randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (\>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day). Standardized dietitians delivere the LSI. The treatment goal is to achieve \>3% weight loss during the 12-week follow-up. Participants are genotyped for the risk allele rs13342232 and rs75493593. The effects of the risk haplotype are evaluated with linear and logistic regressions adjusted by age, sex, five genetic principal components, BMI, and prediabetes criteria at baseline. Primary outcome is a significant interaction between the treatment arm and genotype in weight loss goal \>3% after the treatment. Secondary outcome are differences in lipid levels and third outcome is differences in glycemic parameters (fasting glucose, HbA1c).

Eligibility criteria: Inclusion Criteria:

* Mexican mestizos
* At least one prediabetes criteria according to the American Diabetes Association: fasting glucose between 100-124 mg/dL, Glycosylated hemoglobin (HbA1c) between 5.7-6.4, and 2-hour blood sugar between 140 mg/dl-199 mg/dl after an oral load of 75g of glucose) (1);
* Age ranged between 18-65 years
* Overweight or obesity (BMI between 25.0 - 40 kg/m2).

Exclusion Criteria:

* Chronic diseases
* Pregnancy
* Chronic use of medications that altered plasma glucose levels.

Primary outcomes:
measure: Change in weigth loss
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Total-Cholesterol parameters
timeFrame: 12 weeks
measure: Change in LDL-Cholesterol parameters
timeFrame: 12 weeks
measure: Change in ApoB
timeFrame: 12 weeks
measure: Change in NonHDL-Cholesterol
timeFrame: 12 weeks
measure: Change in fasting glucose
timeFrame: 12 weeks
measure: Change in HbA1c
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Carlos A Aguilar Salinas, PhD
role: PRINCIPAL_INVESTIGATOR
References: