Liver Fat as a Dietary Target for Treating Cardiometabolic Disorders in Prediabetes and Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— NAFLDiet  

Official title:

Liver Fat as a Dietary Target for Treating Cardiometabolic Disorders in Prediabetes and Type 2 Diabetes: a Randomized Study (NAFLDiet)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04527965
• Other study ID #: NAFLDiet
• Status: Completed
• Phase: N/A
• Start date: August 11, 2020
• Est. completion date: December 20, 2022

Study information

• Verified date: December 2022
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall aim of this study is to investigate the long-term impact of a customized diet aimed at reducing liver fat specifically and a healthy Nordic diet on ectopic fat (liver, pancreatic and visceral) and cardiometabolic risk in individuals with prediabetes and type 2 diabetes (T2D).

Description:

Randomized controlled studies investigating the impact of replacing dietary carbohydrates with polyunsaturated fat (PUFA) on liver fat content and cardiometabolic risk in individuals with prediabetes and T2D are lacking. Also, the effects of a Healthy Nordic Diet on liver fat content and glycemic control have not be investigated. This study therefore aims to:

• Investigate the effects of the diets on liver fat content (primary aim)

• Investigate the effects of the diets on pancreatic fat, visceral fat, lean tissue, glycemic and lipid control

• Investigate the effects of the diets on plasma markers of de novo lipogenesis (DNL) and desaturation (i.e. stearoyl-Coenzyme desaturase 1, SCD-1) as well as on hepatic DNL using MRI spectroscopy

• Investigate gene-diet interactions, especially if common gene variants (e.g. in PNPLA3) known to increase liver fat and dyslipidemia, may modify the dietary effects.

• Perform lipidomic analyses to identify potential mechanistic pathways that may associate with diet-induced changes in liver fat, pancreatic fat, visceral fat, insulin sensitivity, dyslipidemia or DNL

Our hypothesis is that a customized diet will effectively reduce liver fat through suppression of hepatic DNL and SCD-1 activity, and thereby improve atherogenic dyslipidemia, insulin resistance and hyperglycemia in individuals with prediabetes and T2D.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 20, 2022
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Men and women

• 30-75 years

• BMI 25-40

• T2D (duration =10 years, no insulin treatment) or prediabetes (ADA definition 2019) without diagnosed cardiovascular disease (CVD) during the last 2 years (e.g. myocardial infarction, stroke or angina pectoris)

Exclusion Criteria:

• BMI >40

• Alcohol intake >20 g/day

• Unwillingness to follow a new prescribed diet for 1 year

• Diet-induced weight loss (=10%) the preceding 3 months of screening

• Malignant disease

• Severe kidney and liver disease

• Heart failure or other severe CVD

• claustrophobia or metal parts in the body (MRI)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• NAFLD
• PreDiabetes
• Prediabetic State

Intervention

Other:
• Customized diet to reduce liver fat
Ad libitum diet high in plant-derived PUFA and lower in carbohydrates Carbohydrates: 30 E% Fat: 50 E% (PUFA 10-15 E%) Protein: 20 E% Key foods are provided
• Healthy Nordic diet
Ad libitum diet, based on Nordic foods, high in carbohydrates (high fiber/low GI) and lower in fat Carbohydrates: 50-55 E% Fat: 25-30 E% (PUFA 5-7.5 E%) Protein: 20 E% Key foods are provided
• Control
Ad libitum diet in accordance with the Nordic Nutrition Recommendations Key foods are provided

Locations

Country	Name	City	State
Sweden	Uppsala univeristy hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Between-group changes in plasma-derived fatty acids and fatty acid ratios in the lipogenic pathway between baseline and month 12	Assessed by gas chromatography (GC)	12 months
Other	Between-group changes in imaging-derived fatty acids and fatty acid ratios in the lipogenic pathway between baseline and month 12	Assessed by proton magnetic resonance spectroscopy (1 H-MRS)	12 months
Other	Between-group changes in plasma lipids (ceramides) using a targeted lipidomic approach between baseline and month 12	Lipids are measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)	12 months
Primary	Between-group changes in liver fat content between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in visceral adipose tissue mass between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in lean tissue mass between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in total body fat mass between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in body weight between baseline and month 12	Assessed by using a Tanita bioelectrical impedance analysis (BIA) scale	12 months
Secondary	Between-group changes in glycated hemoglobin (HbA1c) between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in fasting plasma glucose between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in fasting serum insulin between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in systolic blood pressure between baseline and month 12	Assessed by using an automated blood pressure monitor	12 months
Secondary	Between-group changes in diastolic blood pressure between baseline and month 12	Assessed by using an automated blood pressure monitor	12 months
Secondary	Between-group changes in plasma lipids (total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, apoB and apoA1) between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in circulating inflammatory markers (CRP, Tumor Necrosis Factor Alpha-receptor 1 and 2, Interleukin-1 receptor antagonist, Fibroblast growth factor 21) between baseline and month 12	Assessed by routine clinical chemistry and ELISA	12 months
Secondary	Between-group changes in pancreatic fat between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in flow-mediated dilation (FMD) between baseline and month 12	Assessed by ultrasound in approximately half of the study population (n=75)	12 months
Secondary	Between-group changes in pulse-wave velocity (PWV) between baseline and month 12	Assessed by ultrasound in approximately half of the study population (n=75)	12 months
Secondary	Between-group values in FMD at month 12	Assessed by ultrasound in the whole population (n=150)	12 months
Secondary	Between-group values in PWV at month 12	Assessed by ultrasound in the whole population (n=150)	12 months
Secondary	Between-group changes in liver fat in prespecified subgroups and in individuals with low respectively high dietary compliance based on dietary and lipogenic biomarkers changes between baseline and month 12	Assessed by magnetic resonance imaging (MRI)	12 months
Secondary	Between-group changes in HbA1c in prespecified subgroups and in individuals with low respectively high dietary compliance based on dietary and lipogenic biomarkers changes between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in blood lipids in prespecified subgroups and in individuals with low respectively high dietary compliance based on dietary and lipogenic biomarkers changes between baseline and month 12	Assessed by routine clinical chemistry	12 months
Secondary	Between-group changes in FIB-4 between baseline and month 12	Assessed by routine clinical chemistry in combination with age	12 months