Effect of the SCL16A11 Risk Haplotype on Treatments to Prevent Type 2 Diabetes

Phase 2

Completed

• Conditions: PreDiabetes
• Interventions: Behavioral: Life Style Intervention; Drug: Life Style Intervention + Metformin

• Registration Number: NCT05990205
• Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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).

Study Timeline

• Study Start: 2018-04-17
• Status Verified: 2023-05
• Study First Submitted: 2023-07-18
• Study First Submitted QC: 2023-08-10
• Study First Posted: 2023-08-14
• Primary Completion: 2023-12-20
• Study Completion: 2024-03-01
• Last Update Submitted: 2024-05-23
• Last Update Posted: 2024-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 437

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Life Style Intervention	Life Style Intervention	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)
Life Style Intervention + Metformin	Life Style Intervention + Metformin	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) + (750 mg metformin twice a day).

Primary Outcome Measures

Name	Time	Method
Change in weigth loss	12 weeks	Number of participants in each treatment arm reaching the the goal weight loss \>3%

Secondary Outcome Measures

Name	Time	Method
Change in ApoB	12 weeks	Decreasing ApoB levels (mg/dl)
Change in HbA1c	12 weeks	Decreasin HbA1c levels (%)
Change in NonHDL-Cholesterol	12 weeks	Decreasin NonHDL-Cholesterol levels (mg/dl)
Change in fasting glucose	12 weeks	Decreasing fasting glucose levels (mg/dl)
Change in Total-Cholesterol parameters	12 weeks	Decreasing concentration of Total-Cholesterol (mg/dl)
Change in LDL-Cholesterol parameters	12 weeks	Decreasing LDL-Cholesterol levels (mg/dl)

Trial Locations

Locations (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; 🇲🇽 Mexico City, Mexico