Liver Fat as a Dietary Target of the Chinese Medical Nutrition Therapy (CMNT) Diet for Treating Type 2 Diabetes With Nonalcoholic Fatty Liver Disease

Type 2 diabetes (T2D) represents a serious public health problem. Patients with T2D and non-alcoholic fatty liver disease(NAFLD) demonstrate a poor metabolic profile and increase mortality compared with patients with only NAFLD or T2D. Nutritional intervention is the most basic treatment for T2D. Previous study showed that a Chinese medical nutrition therapy (CMNT) diet, which intermittent use of low-calorie medicinal food, has a glucose-lowering effect in T2D. This study aims to investigate the effect of a Chinese medical nutrition therapy (CMNT) diet accompanied by intermittent energy restriction on reducing liver fat and glycated hemoglobin (HbA1c) in patients with T2D and NAFLD.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: CMNT diet

Detailed Description

Diet composition of CMNT is a multicomponent Chinese medicinal food, which mainly enriched with whole grains and edible medicine and food homologous (MFH) plants such as Rhizoma Dioscoreae, Momordica Grosvenori, Folium Mori, Radix Puerariae, Fructus lycii, Poria cocos that meets the requirements of a food for special medical purpose. The CMNT group was instructed to consumed the provided CMNT diet consisting of 6 cycles of 5 consecutive days followed by 10 days of ad libitum food consumption. Participants received a 917 kcal/day preprepared human CMNT diet (44.75% carbohydrate, 9.1% protein and 46.15% fat) for 5 consecutive days per cycle. CMNT diet is composed of four ready-to-consume prepared foods including composite nutritional rice, solids beverages, meal replacement biscuit and fruit and vegetable gruel mainly from wholegrains and traditional Chinese medicinal food plants. The intervention lasted for 3 months (6 cycles) and follow-up measurements will be performed in all subjects after 3-months from end of the intervention. The glucose-lowering medication use of participants strictly implemented by their physician according to the diabetes medications management protocol. Treatment-as-usual control group continued to be given standard medication and dietary advice by their physician followed guidelines for the prevention and control of T2D in China.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luo wu; Phone Number: 13687333270; Email: luowubio@163.com
• Study Contact Backup: Name: Yang xiao; Phone Number: 15200877395; Email: 31884210@qq.com

Study Locations

• China
  • Hubei
    • Yichang, Hubei, China
      • Recruiting
      • Physical Examination Center of Gezhouba central hospital of Sinopharm
      • Contact: Jian Li; Email: 18942546818@163.com
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Jinheyuan Outpatient Department, National Sub-health Intervention Technology Achievement Application Center
      • Contact: Xiao Yang; Email: 31884210@qq.com
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Shanshui physical examination center
      • Contact: Wu Luo; Email: luowubio@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with type 2 diabetes and NAFLD
• Age between 18 and 75 years
• BMI between 18.0 and 35.0 kg/m2
• Weight stable for at least 3 months prior to the study (gain or loss < 4 kg)
• Stable treatment for at least 3 months with 1-3 oral antidiabetic medications (with or without insulin therapy), or not yet received antidiabetic medication prior to the beginning of the study
• Able to give written informed consent

Exclusion Criteria:

• Self-reported a food allergy
• Alcohol abuse in the last 3 months (alcohol intake greater than 20 g per day for women; Alcohol intake for men greater than 40 g per day)
• Other liver diseases such as chronic hepatitis B and C, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, nodular regenerative hyperplasia and focal nodular hyperplasia
• Scheduled to be hospitalized for any surgical treatment during screening
• Pregnant or planning of pregnancy during the study
• Inability, physically or mentally, to adhere the procedures required by the study protocol
• Level 3 hypoglycemic events (at least 3 times) occurring within the 90 days prior to screening
• Hospitalization or emergency department visit for hyperglycemia, diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic coma, or diabetes
• History of cancer within the past 5 years
• Acute coronary or cerebrovascular event in the past 90 days, or heart failure
• Hemorrhagic or ischemic stroke within the last 6 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMNT diet; The CMNT group was instructed to consumed the provided CMNT diet consisting of 6 cycles of 5 consecutive days followed by 10 days of ad libitum food consumption. Participants received a 917 kcal/day preprepared human CMNT diet (44.75% carbohydrate, 9.1% protein and 46.15% fat) for 5 consecutive days per cycle	Other: CMNT diet; Hypocaloric CMNT diet plan: A diet plan with intermittent use of enriched traditional-Chinese-medicinal-foods CMNT diet
No Intervention: Usual Care; Dietary recommendations based on the Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) as the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controlled attenuation parameter (CAP) value by transient elastography	The CAP score, which be measured by FibroScan, will be used to quantify and detect liver fat. CAP < 238 dB/m indicated no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild steatosis, 260 ≤ CAP ≤291 dB/m indicated moderate steatosis, and CAP > 291 dB/m denoted severe steatosis.	3, 6, 12, 24 months
HbA1C	Blood test to measure glucose control	3, 6, 12, 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty liver index (FLI)	FLI will also be applied to quantify the degree of steatosis of patients with type 2 diabetes and NAFLD. FLI values < 30 rule out liver steatosis, whereas FLI ≥ 60 confirmed NAFLD with a specificity of 61%.	3, 6, 12, 24 months
Hepatic steatosis index (HSI)	HSI will also be applied to quantify the degree of steatosis of patients with type 2 diabetes and NAFLD. HSI values < 30 excludes NAFLD with a sensitivity of 93.1%, while values > 36 detected NAFLD with a specificity of 92.4%.	3, 6, 12, 24 months
Liver stiffness measurement (LSM) value by transient elastography	Liver fibrosis will be assessed by using a non-invasive vibration-controlled transient elastography to estimate LSM. A median LSM ≥ 8.2 kPa was considered indicative of significant fibrosis (≥ F2), whereas LSM ≥ 9.7 kPa was considered indicative of advanced (≥ F3) fibrosis, whereas LSM ≥ 13.6 kPa was considered indicative of cirrhosis (F4).	3, 6, 12, 24 months
Fibrosis-4 index (FIB-4)	The FIB-4 index, a non-invasive measurement, will be used to evaluate the degree of liver fibrosis. The FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude progressive fibrosis, whereas FIB-4 index >3.25 was considered advanced fibrosis or cirrhosis.	3, 6, 12, 24 months
NAFLD fibrosis score (NFS)	Degree of liver fibrosis will also be assessed by NFS.The probability of advanced liver fibrosis was classified into three groups: high NFS (NFS > 0.676), intermediate NFS (NFS: -1.455 to 0.676, or 0.120 to 0.676 if age > 65), or low NFS (NFS < -1.455, or < 0.120 if age > 65) .	3, 6, 12, 24 months
Liver function test	γ-glutamyl transferase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and ect will be assessed.	3, 6, 12, 24 months
Blood glucose	Fasting plasma glucose (FPG) and postprandial 2-hour plasma glucose (2 h-PG)	3, 6, 12, 24 months
Blood lipid	triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)	3, 6, 12, 24 months
Insulin	Glucose homeostasis	3, 6, 12, 24 months
HOMA-IR	Fasting glucose times fasting insulin divided by 22.5	3, 6, 12, 24 months
IGF-1	Glucose homeostasis	3, 6, 12, 24 months
Body mass index	Body mass in kilograms divided by height in meters squared.	3, 6, 12, 24 months
waist-to-hip ratio	Waist circumference in centimeter divided by height in centimeter.	3, 6, 12, 24 months
Blood pressure	Systolic blood pressure and diastolic blood pressure.	3, 6, 12, 24 months
Energy intake	3-day diet record and Food Frequency Questionnaire	3, 6, 12, 24 months
Macronutrient intake	3-day diet record and Food Frequency Questionnaire	3, 6, 12, 24 months
Sleep quality	Pittsburgh Sleep Quality Index Questionnaire	3, 6, 12, 24 months
Physical activity	International Physical Activity Questionnaire	3, 6, 12, 24 months
Self-reported depressive symptoms	Patient Health Questionnaire 9	3, 6, 12, 24 months
Anxiety symptoms	Generalized Anxiety Disorder scale	3, 6, 12, 24 months
Social support	Social Support Rate Scale	3, 6, 12, 24 months
Reduction in glucose-lowering medication	Reduction in total dose of glucose-lowering medications	3, 6, 12, 24 months
Fecal microbiota profile	Fecal samples will be collected and will be sequenced.	3, 6, 12, 24 months
Metabolomics	Blood, fecal and urine samples will be collected and metabolites will be analyzed through a metabolomics approach.	3, 6, 12, 24 months

Collaborators and Investigators

• Sponsor: State Key Laboratory of Subhealth Intervention Technology

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): June 20, 2023
• Study Completion (Estimated): May 5, 2024

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Type 2 Diabetes with NAFLD; CMNT diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: Version 2.0 (Sponsor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No