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

Not Applicable
Recruiting
Conditions
Type 2 Diabetes
Interventions
Other: CMNT diet
Registration Number
NCT05439226
Lead Sponsor
State Key Laboratory of Subhealth Intervention Technology
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CMNT dietCMNT dietThe 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
Primary Outcome Measures
NameTimeMethod
HbA1C3, 6, 12, 24 months

Blood test to measure glucose control

Controlled attenuation parameter (CAP) value by transient elastography3, 6, 12, 24 months

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.

Secondary Outcome Measures
NameTimeMethod
Fatty liver index (FLI)3, 6, 12, 24 months

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%.

Hepatic steatosis index (HSI)3, 6, 12, 24 months

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%.

Fibrosis-4 index (FIB-4)3, 6, 12, 24 months

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.

NAFLD fibrosis score (NFS)3, 6, 12, 24 months

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) .

HOMA-IR3, 6, 12, 24 months

Fasting glucose times fasting insulin divided by 22.5

IGF-13, 6, 12, 24 months

Glucose homeostasis

Liver stiffness measurement (LSM) value by transient elastography3, 6, 12, 24 months

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).

Liver function test3, 6, 12, 24 months

γ-glutamyl transferase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and ect will be assessed.

Reduction in glucose-lowering medication3, 6, 12, 24 months

Reduction in total dose of glucose-lowering medications

Body mass index3, 6, 12, 24 months

Body mass in kilograms divided by height in meters squared.

waist-to-hip ratio3, 6, 12, 24 months

Waist circumference in centimeter divided by height in centimeter.

Blood pressure3, 6, 12, 24 months

Systolic blood pressure and diastolic blood pressure.

Energy intake3, 6, 12, 24 months

3-day diet record and Food Frequency Questionnaire

Anxiety symptoms3, 6, 12, 24 months

Generalized Anxiety Disorder scale

Social support3, 6, 12, 24 months

Social Support Rate Scale

Fecal microbiota profile3, 6, 12, 24 months

Fecal samples will be collected and will be sequenced.

Metabolomics3, 6, 12, 24 months

Blood, fecal and urine samples will be collected and metabolites will be analyzed through a metabolomics approach.

Blood lipid3, 6, 12, 24 months

triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)

Macronutrient intake3, 6, 12, 24 months

3-day diet record and Food Frequency Questionnaire

Blood glucose3, 6, 12, 24 months

Fasting plasma glucose (FPG) and postprandial 2-hour plasma glucose (2 h-PG)

Insulin3, 6, 12, 24 months

Glucose homeostasis

Sleep quality3, 6, 12, 24 months

Pittsburgh Sleep Quality Index Questionnaire

Physical activity3, 6, 12, 24 months

International Physical Activity Questionnaire

Self-reported depressive symptoms3, 6, 12, 24 months

Patient Health Questionnaire 9

Trial Locations

Locations (3)

Physical Examination Center of Gezhouba central hospital of Sinopharm

🇨🇳

Yichang, Hubei, China

Hunan Shanshui physical examination center

🇨🇳

Changsha, Hunan, China

Jinheyuan Outpatient Department, National Sub-health Intervention Technology Achievement Application Center

🇨🇳

Changsha, Hunan, China

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