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Completed

NCT Number: NCT04527965

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

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).

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Key information

Conditions

NAFLD Diabetes Mellitus Diabetes Mellitus, Type 2 Digestive System Diseases Endocrine System Diseases Fatty Liver Glucose Metabolism Disorders Liver Diseases Metabolic Diseases Non-alcoholic Fatty Liver Disease Nutritional and Metabolic Diseases PreDiabetes Prediabetic State

Age range

30 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Uppsala univeristy hospital

Uppsala, 75185, Sweden

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Customized diet to reduce liver fat

Other

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

Other

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

Other

Ad libitum diet in accordance with the Nordic Nutrition Recommendations

Key foods are provided

Primary outcomes

  1. Between-group changes in liver fat content between baseline and month 12

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

Secondary outcomes

  1. Between-group changes in visceral adipose tissue mass between baseline and month 12

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

  2. Between-group changes in lean tissue mass between baseline and month 12

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

  3. Between-group changes in total body fat mass between baseline and month 12

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

  4. Between-group changes in body weight between baseline and month 12

    Time frame: 12 months

    Assessed by using a Tanita bioelectrical impedance analysis (BIA) scale

  5. Between-group changes in glycated hemoglobin (HbA1c) between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry

  6. Between-group changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry

  7. Between-group changes in fasting plasma glucose between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry

  8. Between-group changes in fasting serum insulin between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry

  9. Between-group changes in systolic blood pressure between baseline and month 12

    Time frame: 12 months

    Assessed by using an automated blood pressure monitor

  10. Between-group changes in diastolic blood pressure between baseline and month 12

    Time frame: 12 months

    Assessed by using an automated blood pressure monitor

  11. Between-group changes in plasma lipids (total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, apoB and apoA1) between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry

  12. 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

    Time frame: 12 months

    Assessed by routine clinical chemistry and ELISA

  13. Between-group changes in pancreatic fat between baseline and month 12

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

  14. Between-group changes in flow-mediated dilation (FMD) between baseline and month 12

    Time frame: 12 months

    Assessed by ultrasound in approximately half of the study population (n=75)

  15. Between-group changes in pulse-wave velocity (PWV) between baseline and month 12

    Time frame: 12 months

    Assessed by ultrasound in approximately half of the study population (n=75)

  16. Between-group values in FMD at month 12

    Time frame: 12 months

    Assessed by ultrasound in the whole population (n=150)

  17. Between-group values in PWV at month 12

    Time frame: 12 months

    Assessed by ultrasound in the whole population (n=150)

  18. 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

    Time frame: 12 months

    Assessed by magnetic resonance imaging (MRI)

  19. 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

    Time frame: 12 months

    Assessed by routine clinical chemistry

  20. 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

    Time frame: 12 months

    Assessed by routine clinical chemistry

  21. Between-group changes in FIB-4 between baseline and month 12

    Time frame: 12 months

    Assessed by routine clinical chemistry in combination with age

Other outcomes

  1. Between-group changes in plasma-derived fatty acids and fatty acid ratios in the lipogenic pathway between baseline and month 12

    Time frame: 12 months

    Assessed by gas chromatography (GC)

  2. Between-group changes in imaging-derived fatty acids and fatty acid ratios in the lipogenic pathway between baseline and month 12

    Time frame: 12 months

    Assessed by proton magnetic resonance spectroscopy (1 H-MRS)

  3. Between-group changes in plasma lipids (ceramides) using a targeted lipidomic approach between baseline and month 12

    Time frame: 12 months

    Lipids are measured using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)

Sponsors and collaborators

Lead sponsor

Uppsala University

Other

Registry information

Official study title

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

Acronym: NAFLDiet

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Aug 27, 2020
Registry last updated
Dec 22, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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