Low-Carbohydrate Dietary Pattern on Glycemic Outcomes Trial

Study Overview
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Brief Summary
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The proposed randomized controlled trial will test the effect of a low-carbohydrate diet on hemoglobin A1c among individuals with elevated hemoglobin A1c that are within the range of prediabetes or diabetes. Results may provide evidence about the role of carbohydrate restriction in individuals with or at high risk of type 2 diabetes.

Detailed Description
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In the short-term, among patients with type 2 diabetes, low-to-moderate carbohydrate diets have a greater glucose-lowering effect than do high-carbohydrate diets. However, compared with usual diet, the effect of a behavioral intervention promoting a low-carbohydrate/high-unsaturated fat and high-protein dietary pattern among individuals with prediabetes or untreated type 2 diabetes is not well understood. The overall goal of this randomized controlled trial is to study the effect of a behavioral intervention promoting a low-carbohydrate/high-unsaturated fat and high-protein dietary pattern compared with usual diet on hemoglobin A1c (HbA1c) and other metabolic risk factors among individuals with or at high risk of diabetes (HbA1c 6.0-6.9%). A total of 150 participants with HbA1c 6.0-6.9% will be recruited and randomly assigned to either a 6-month behavioral modification program designed to reduce carbohydrate intake (initial target <40 g digestible carbohydrates, final target <60 g digestible carbohydrates) or to usual diet in a 1:1 randomization ratio. The primary outcome will be the difference between the active intervention and control groups for change in HbA1c from baseline to 6 months. Secondary outcomes will be fasting glucose, systolic blood pressure, total-to-high-density lipoprotein-cholesterol ratio, and body weight. Findings from this study may provide evidence about the role of carbohydrate restriction in individuals with or at high risk of type 2 diabetes.

Official Title
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Low-Carbohydrate Dietary Pattern on Glycemic Outcomes Trial

Conditions
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Diabetes, PreDiabetes, Metabolic Disease, Hyperglycemia, Diet Modification, Glucose Intolerance, Glucose Metabolism Disorders (Including Diabetes Mellitus), Endocrine System Diseases

Intervention / Treatment
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* Behavioral: Low-Carbohydrate Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ages 40 to 70 years HbA1c 6.0-6.9% Willing and able to provide informed consent Exclusion Criteria: Diagnosed type 1 diabetes mellitus Use of agents affecting glycemic control (medications for diabetes, oral glucocorticoids) within the past three months prior to enrollment Medical condition in which low-carbohydrate diet may not be advised: estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m²; self-report of liver disease due to hepatitis or alcohol; osteoporosis; untreated thyroid disease; gout; cancer (other than non-melanoma skin cancer) requiring treatment in the past year, unless prognosis is excellent Factors that may affect HbA1c: hemoglobin <11 mg/dL (cutpoint for moderate-to-severe anemia, which could lead to falsely elevated or lowered HbA1c); recent blood donation or blood transfusion (self-report, past 4 months); human immunodeficiency virus (self-report) Self-reported history of intensive care unit stay due to Coronavirus Disease 2019 (COVID-19) in the past three months, as severe COVID-19 may affect blood glucose levels Allergies to nuts For women, current pregnancy, breastfeeding, or plans to become pregnant during the study Consumption of ≥21 alcoholic drinks per week or consumption of ≥6 drinks per occasion Current or planned residence making it difficult to meet trial requirements (due to distance from study site and/or challenges regularly traveling to site) Current participation in another lifestyle intervention trial or a pharmaceutical trial Participation of another household member in the study; employees or persons living with employees of the study Other concerns regarding ability to meet trial requirements, at the discretion of the principal investigator or study coordinator

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Carbohydrate Diet<br>Behavioral modification to reduce carbohydrate consumption. Target <40 g net carbohydrates per day for first 3 months; <60 g net carbohydrates per day for months 4 onwards. The intervention will consist of 4 weekly individual counseling sessions, followed by 4 group sessions held every other week, with phone follow-ups in between group sessions. For the last 3 months of the study, there will be 3 monthly group sessions and 3 telephone follow-ups. At baseline, participants will receive written information with standard physical activity recommendations. | Behavioral: Low-Carbohydrate Diet<br>* Behavioral modification to reduce carbohydrate consumption. Target <40 g net carbohydrates per day for first 3 months; <60 g net carbohydrates per day for months 4 onwards. The intervention will consist of 4 weekly individual counseling sessions, followed by 4 group sessions held every other week, with phone follow-ups in between group sessions. For the last 3 months of the study, there will be 3 monthly group sessions and 3 telephone follow-ups. At baseline, participants will receive written information with standard physical activity recommendations.<br>|
| No Intervention: Usual Diet<br>No dietary intervention. At baseline, participants will receive written information with standard dietary advice and standard physical activity recommendations. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c | 6-month change in Hemoglobin A1c comparing low-carbohydrate arm with usual diet arm | Baseline and six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose | 6-month change in fasting plasma glucose comparing low-carbohydrate arm with usual diet arm | Baseline and six months | 
| Change in Systolic Blood Pressure | 6-month change in systolic blood pressure comparing low-carbohydrate arm with usual diet arm | Baseline and six months | 
| Change in Total-to-HDL-cholesterol Ratio | 6-month change in total-to-HDL-cholesterol ratio comparing low-carbohydrate arm with usual diet arm | Baseline and six months | 
| Change in Body Weight | 6-month change in body weight comparing low-carbohydrate arm with usual diet arm | Baseline and six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prediabetes, Diabetes, Low-Carbohydrate Diet