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

Uppsala University

Status: Completed

Conditions: NAFLD; Diabetes Mellitus, Type 2; PreDiabetes

Treatments: Other: Customized diet to reduce liver fat; Other: Healthy Nordic diet; Other: Control

Study type: Interventional

Funder types: Other

Identifiers

NCT04527965

NAFLDiet

Details and patient eligibility

About

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).

Full 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.

Enrollment: 150 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 3 patient groups

Customized diet to reduce liver fat

Experimental group

Description:

Ad libitum diet high in plant-derived PUFA and lower in carbohydrates

Treatment:

Other: Customized diet to reduce liver fat

Healthy Nordic diet

Experimental group

Description:

Ad libitum diet, based on Nordic foods, higher in carbohydrates (high fiber/low GI) and lower in fat but rich in monounsaturated fatty acids (MUFA) and PUFA

Treatment:

Other: Healthy Nordic diet

Control

Active Comparator group

Description:

Ad libitum diet in accordance with the Nordic Nutrition Recommendations

Treatment:

Other: Control