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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
150
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
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
Ad libitum diet in accordance with the Nordic Nutrition Recommendations Key foods are provided
Uppsala univeristy hospital
Uppsala, Sweden
Between-group changes in liver fat content between baseline and month 12
Assessed by magnetic resonance imaging (MRI)
Time frame: 12 months
Between-group changes in visceral adipose tissue mass between baseline and month 12
Assessed by magnetic resonance imaging (MRI)
Time frame: 12 months
Between-group changes in lean tissue mass between baseline and month 12
Assessed by magnetic resonance imaging (MRI)
Time frame: 12 months
Between-group changes in total body fat mass between baseline and month 12
Assessed by magnetic resonance imaging (MRI)
Time frame: 12 months
Between-group changes in body weight between baseline and month 12
Assessed by using a Tanita bioelectrical impedance analysis (BIA) scale
Time frame: 12 months
Between-group changes in glycated hemoglobin (HbA1c) between baseline and month 12
Assessed by routine clinical chemistry
Time frame: 12 months
Between-group changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) between baseline and month 12
Assessed by routine clinical chemistry
Time frame: 12 months
Between-group changes in fasting plasma glucose between baseline and month 12
Assessed by routine clinical chemistry
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Time frame: 12 months
Between-group changes in fasting serum insulin between baseline and month 12
Assessed by routine clinical chemistry
Time frame: 12 months
Between-group changes in systolic blood pressure between baseline and month 12
Assessed by using an automated blood pressure monitor
Time frame: 12 months
Between-group changes in diastolic blood pressure between baseline and month 12
Assessed by using an automated blood pressure monitor
Time frame: 12 months
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
Time frame: 12 months
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
Time frame: 12 months
Between-group changes in pancreatic fat between baseline and month 12
Assessed by magnetic resonance imaging (MRI)
Time frame: 12 months
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)
Time frame: 12 months
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)
Time frame: 12 months
Between-group values in FMD at month 12
Assessed by ultrasound in the whole population (n=150)
Time frame: 12 months
Between-group values in PWV at month 12
Assessed by ultrasound in the whole population (n=150)
Time frame: 12 months
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)
Time frame: 12 months
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
Time frame: 12 months
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
Time frame: 12 months
Between-group changes in FIB-4 between baseline and month 12
Assessed by routine clinical chemistry in combination with age
Time frame: 12 months