Metabolism of Low Carbohydrate and Ketogenic Diet

Precision Metabolic Mechanisms of Low Carbohydrate and Ketogenic Diet

This study will assess the preliminary efficacy of a lifestyle intervention including low-carb/ketogenic diet and exercise, enhanced by self-monitoring through health technologies on weight and diabetes outcomes (Glucose, HbA1c) and diabetic complications (cognitive function, and renal function) in a 6-month randomized clinical trial in 60 overweight/obese adults with or without T2D. Renal function will be assessed via both traditional and novel biomarkers, including novel metabolites and mitochondrial function.

Study Overview

• Status: Completed
• Conditions: Diabetic Kidney Disease; Weight Loss; Cognitive Function; Type2 Diabetes; Diabetic Control
• Intervention / Treatment: Other: mHealth + low-fat diet; Other: mHealth + low-carb/ketogenic diet

Detailed Description

Participants in both groups will receive standardized health education sessions including lifestyle management, blood glucose control, blood pressure control, and prevention of diabetic complications from trained providers who are also investigators of this study. The lifestyle intervention from the evidence-based Group Lifestyle Balance (GLB) program (http://www.diabetesprevention.pitt.edu/index.php/for-the-public/for-health-providers/group-lifestyle-balance-curriculum/) and Look AHEAD intervention (https://www.lookaheadtrial.org) will be modified for this study. Goal for weight loss and physical activity will be set for each participant based on recommendations from GLB and Look AHEAD. Lifestyle intervention will be delivered through interactive digital lessons. Smart phone and mobile health devices will be used for each participant to self-monitor diet, physical activity, weight, glucose level, blood pressure, and blood ketone (if randomized to the low-car/ketogenic diet group).

Control group (mHealth+ low-fat diet group):

The low-fat group will be asked to restrict total calorie and total fat consumption according to the Look AHEAD intervention and MyPlate guidelines, with 26-44% carbs, 10-30% protein, and less than 30% fat.

Intervention group (mHealth+ low-carb/ketogenic diet group):

The low-carb/ketogenic diet group, will have total calorie set according to Look AHEAD intervention, and carb consumption restriction will be set based on recommendations from American Diabetic Association, National Kidney Foundation, and other evidence-based resources. Participants in this group will be asked to consume a low-carb/ketogenic diet. Specially, participants will receive a carbohydrate, protein, and fat intake goal based on 1.5 : 1 ratio (1.5 grams of fat to 1 gram of carbohydrate and protein combined). Daily macronutrient and calorie consumption will be individualized for each participant using ideal body weight as inferred from wrist circumference and activity level. Carbohydrate consumption will be less than 10% (20~50 g), protein 10-20% (1.0~1.2g/kg ideal body weight), and fat 70-80% of total daily energy, respectively. Nutritional ketosis will be reached by consuming such diet (0.5 mmol/L).

All diet intervention materials will be developed by a registered dietitian according to the evidence-based guidelines. The dietitian will also be responsible to any study activities relevant to diet. These activities include but are not limited to responding to some specific diet questions to study participants and health related measurements relevant to diet changes.

An interventionist, under supervision of a registered dietitian, will interact with each participant from both groups at the beginning of the intervention as an introduction visit, and three individual intervention sessions at month 1, 3, and 5. During the introduction visit, the interventionist will set up a personalized weight loss goal and caloric intake goal with the participants. The individual intervention sessions at month 1, 3 and 5 will be arranged to solve the encountered problems regarding diet, weight loss, caloric intake and action planning.

Additional communication through phone call will be used to support patient dietary changes throughout the study based on their self-monitoring information.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio School of Nursing
    • San Antonio, Texas, United States, 78207
      • University Health System Texas Diabetic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing to participate in the study
2. being 18 and over

3. For overweight/obese adults (BMI≥25kg/m2)

   1. without self-reported diagnosis of Type 2 Diabetes (T2D) or Chronic Kidney Disease (CKD): Estimated Glomerular Filtration Rate (eGFR)≥90mL/min/1.73m2 and urine albumin to creatinine ratio (ACR)<30mg/g within the past 12 months
   2. with Type 2 Diabetes (T2D) but without Chronic Kidney Disease (CKD): Estimated glomerular filtration rate (eGFR)≥90mL/min/1.73m2 and Albumin-to-Creatinine ratio (ACR)<30mg/g within the past 12 months
   3. with early stage Chronic Kidney Disease (CKD): 60≤eGFR<90mL/min/1.73m2 or 30mg/g ≤ACR< 1000mg/g within the 12 months
4. can speak and understand English
5. own a smart phone or tablet that has reliable internet/data access
6. agree to comply with all study requirements

Exclusion Criteria:

1. Patients with triglyceride ≥ 500 mg/dL or with Low-Density Lipoprotein Cholesterol≥ 129mg/dL
2. type 1 diabetes (by self-report)
3. severe psychiatric disorders deemed by investigators, which might interfere with study procedures (by self-report)
4. severe chronic conditions (e.g. severe heart disease, renal disease, cognitive impairment, etc.) that would preclude them from participating
5. unwillingness to sign the consent form and be randomized into a study group
6. enrollment in other low carb/keto diet or weight loss programs
7. inability to walk without assistance (by self-report)
8. under SGLT2 inhibitor treatment
9. being pregnant or breast feeding (by self-report)
10. having plans to leave the city or USA for over 2 weeks within 6 months at enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group (mHealth+low-fat diet group); The low-fat group will be asked to restrict total calorie and total fat consumption according to the Look AHEAD intervention and MyPlate guidelines, with 26-44% carbs, 10-30% protein, and less than 30% fat.	Other: mHealth + low-fat diet; A restricted total calorie and reduced total fat consumption.
Experimental: Intervention Group (mHealth + low-carbohydrate/ketogenic diet group); Total calories will be set according to Look AHEAD intervention, and carbohydrate consumption restriction will be set based on recommendations from American Diabetic Association, National Kidney Foundation, and other evidence-based resources. Participants in this group will be asked to consume a low-carb/ketogenic diet. Specially, participants will receive a carbohydrate, protein, and fat intake goal based on 1.5 : 1 ratio (1.5 grams of fat to 1 gram of carbohydrate and protein combined). Daily macronutrient and calorie consumption will be individualized for each participant using ideal body weight as inferred from wrist circumference and activity level. Carbohydrate consumption will be less than 10% (20~50 g), protein 10-20% (1.0~1.2g/kg ideal body weight), and fat 70-80% of total daily energy, respectively. Nutritional ketosis will be reached by consuming such diet (0.5 mmol/L).	Other: mHealth + low-carb/ketogenic diet; A low-carb/ketogenic diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Measure of weight change that occurred while assigned to the diet	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mitochondrial DNA	Measure of change of mitochondrial function using blood and urine levels	Baseline to 6 months
BMI	BMI (Body Mass Index) is a numerical value derived from a person's weight and height, used as a screening tool to classify individuals into weight categories. It is calculated using weight (kg) divided by height (m)2.	Baseline to 6 months
HbA1c	HbA1c (Hemoglobin A1c) is a blood test that measures the average blood glucose levels over the past 2 to 3 months.	Baseline to 6 months
Blood pressure	Blood Pressure (BP) is the force exerted by circulating blood against the walls of the arteries. It is measured in millimeters of mercury (mmHg) and recorded as two values: Systolic Pressure and Diastolic Pressure.	Baseline to 6 months
Blood lipids	Blood lipids refer to the fatty substances found in the bloodstream, including cholesterol and triglycerides.	Baseline to 6 months
Estimated Glomerular Filtration rate (eGFR)	Measure of change in eGFR in a blood sample.	Baseline to 6 months
Albumin-to-Creatinine ratio (ACR)	Measure of the change in ACR in urine.	Baseline to 6 months
Metabolites	Metabolites are small molecules that are intermediates or end products of metabolism.	Baseline to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment (MoCA)	A one page, 30-point test administered to test cognition. MoCA scores range between 0 and 30. A score of 26 or over is considered to have no cognitive impairment, while lower scores imply more cognitive impairment. Tasks include short term memory recall, visuospatial ability tests, attention, concentration and working memory evaluation and language skills.	Baseline to 6 months
Gut Metabolomics	Measure of changes of gut metabolites using mass spectroscopy.	Baseline to 6 months

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Yan Du, PhD MPH RN, University of Texas Health San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2021
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): October 11, 2022

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Weight loss; Renal function; Healthy lifestyle intervention
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Body Weight; Body Weight Changes; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Complications; Weight Loss; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: HSC20190528H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The plan to make Individual Participant Data (IPD) available to other researchers has not been decided.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No