Design of a Genetic Score to Predict the Response to a Dietary Intervention in Adults With Metabolic Syndrome

Study Overview
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Brief Summary
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The aim of this study is to evaluate whether a genetic score based on genetic variants related to amino acid metabolism could predict the response to a dietary intervention in adults with metabolic syndrome.

Detailed Description
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Metabolic syndrome (MetS) results from the interaction between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) are within the genetic factors. Various SNPs influence amino acid metabolism, and therefore their plasma concentrations. For example, the presence of SNPs such as rs10211524 (SLC1A4), rs9637599 (PPM1K), rs7406661 (ASGR), rs4788815 (TAT), rs199999090, rs11548193 (BCAT2), and rs45500792 (BCKDH), among others, have been related to alterations in the plasma concentration of amino acids. High plasma concentration of amino acids, specifically of branched chain amino acids (BCAA), have a positive association with the presence of different risk factors for MetS including waist circumference, dyslipidemia, blood pressure, glucose concentration and insulin resistance (IR). Moreover, subjects with MetS have a plasma BCAA concentration of up to 34% higher than subjects without MetS. In the other hand, dietary interventions are among the environmental factors that can prevent MetS. For example, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) in the United States recommends a low saturated fat diet (LSFD) to reduce LDL cholesterol. Although, this recommendation has been suggested to attenuate some of the metabolic abnormalities in individuals with MetS, there is no biological marker that can identify individuals who will respond to a LSFD. Notably, the presence of SNPs could help to identify those individuals. The clinical effects exhibited by SNPs when analyzed individually are generally small. For this reason, it has been sought to evaluate the contributory effects of multiple SNPs by means of a genetic score. The construction of a genetic score could capture the complex relationship between MetS, genetics, and dietary interventions, providing us with a greater understanding of the biochemical and metabolic alterations and responses to available treatments. Furthermore, a genetic score could have a therapeutic value in predicting the response to a dietary intervention in subjects with risk factors for MetS. Predicting the response to a dietary intervention may help implement individualized diets based on the genetic predisposition and clinical characteristics of each individual, showing beneficial effects on anthropometric, clinical and biochemical markers. Likewise, implementing dietary interventions for preventive purposes for complex diseases could minimize public health expenditures. Adults will be invited to participate through advertising distributed in the City of San Luis Potosí, Mexico. Those interested in participating will be given a short telephone interview to verify that they meet the selection criteria. Then, an appointment will be scheduled to go to the Faculty of Chemical Sciences of the Autonomous University of San Luis Potosí (UASLP). During this visit, participants will be informed of the characteristics of the study, the risks and the benefits expected after the dietary intervention. Those who accept to participate will sign the consent letter. Then a clinical a nutritional assessment will be performed. A blood sample and blood pressure will be taken by a specialist. Anthropometric and body composition measurements will be made. An history of food consumption frequency will be obtained by a nutritionist. The physical activity questionnaire will be carried out (IPAQ long version). The patient will be advised not to change the level of habitual physical activity. Participants will be then assigned a diet for two months following the indications of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) program. The follow-up of the diet will be evaluated by telephone by a nutritionist who will carry out 24-hour reminder questionnaires randomly every 15 days to each participant. After the first visit, participants will start consuming the diet corresponding to their group. The different menus will be delivered and explained to them. A food guide will be given so that they have food exchange options. Patients will be taught to fill the feed log and will be cited in two months. During the second visit, the investigators will collect a 24-hour dietary record, food logs and the investigators will perform a second clinical and nutritional assessment, including the determination of anthropometric measurements such as weight, waist circumference and body composition, whole blood sample and blood pressure will be taken. The physical activity questionnaire will be carried out (IPAQ long version). Finally, participants will be scheduled within fifteen days for delivery of results and to explain the actions that will be carried out at the end of the study to maintain the continuity of the treatment.

Official Title
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Design of a Genetic Score to Predict the Response to a Dietary Intervention in Adults With Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Other: ATP III dietary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (men and women) between the ages of 18 and 60. Adults mexican mestizos (parents and grandparents born in Mexico). Adults who can read and write. Adults willing/able to provide informed consent. Adults with obesity (BMI ≥ 30 and ≤ 39 kg / m2). Adults with at least one of the metabolic syndrome diagnostic criteria: Waist circumference: men > 102 cm or women > 88 cm. Hypertriglyceridemia >150 mg/dL High fasting glucose >100 mg/dL High blood pressure ≥ 130/85 mmHg Low HDL-cholesterol: men <40 mg/dL and women < 50 mg/dL Exclusion Criteria: Adults with any type of diabetes. Adults with hypertension. Adults with kidney disease diagnosed by a medical or with creatinine> 1.3 mg / dL for men and > 1.1 mg / dL for women and / or blood urea nitrogen (BUN)> 20 mg / dL. Adults with acquired diseases that produce obesity and diabetes secondarily. Adults who have suffered a cardiovascular event. Adults with weight loss > 3 kg in the last 3 months. Adults with any catabolic diseases such as cancer and/or AIDS. Gravidity status Adults who smoke Adults in treatment with any medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Intervention<br>Participants will be assigned a diet for two months following the indications of the National Cholesterol Education Program Adult Treatment Panel III program. | Other: ATP III dietary intervention<br>* The dietary intervention will consist of an approximate decrease of 500 kcal from the calories participants habitually consume, with the following macronutrient distribution 15-20% protein, 50-60% carbohydrates, 25-35% fat. Participants will receive recipes with menus for two weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in waist circumference | Change in waist circumference before and after the dietary intervention (cm) | Baseline to 2-month | 
| Change in serum glucose | The concentration of serum glucose will be determined by an autoanalyzer before and after the intervention | Baseline to 2-month | 
| Change in serum HDL cholesterol | The concentration of serum HDL-cholesterol will be determined by an autoanalyzer before and after the intervention (mg/dL) | Baseline to 2-month | 
| Change in serum triglycerides | The concentration of serum triglycerides will be determined by an autoanalyzer before and after the intervention (mg/dL) | Baseline to 2-month | 
| Change in systolic and diastolic blood pressure | The blood pressure will be determined before and after the intervention (mmHg) | Baseline to 2-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the serum amino acid profile | The concentration of the amino acid profile will be determined by high pressure liquid chromatography (HPLC) before and after the dietary intervention | Baseline to 2-month | 
| Change in body composition | Change in the percentage of fat mass, lean mass and skeletal muscle mass before and after the dietary intervention. | Baseline to 2-month | 
| Change in body weight | The change in body weight before and after the dietary intervention. | Baseline to 2-month | 
| Change in serum insulin | The concentration of insulin will be determined by ELISA before and after the dietary intervention | Baseline to 2-month | 
| Change in serum leptin | The concentration of leptin will be determined by ELISA before and after the dietary intervention | Baseline to 2-month | 
| Change in serum glucagon | The concentration of glucagon will be determined by ELISA before and after the dietary intervention | Baseline to 2-month | 
| Change in serum adiponectin | The concentration of adiponectin will be determined by ELISA before and after the dietary intervention | Baseline to 2-month | 
| Change of insulin resistance by homeostasis model assessment (HOMA) index | The HOMA index will be calculated as follows: glucose (mg / dl) x insulin (mUI / ml) / 405 before and after the dietary intervention | Baseline to 2-month | 
| Change of Body mass index | The body mass index will be calculated before an after the dietary intervention. | Baseline to 2-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic score, Amino acids metabolism, ATPIII