In this project, the investigators will perform a multicenter randomised controlled trial to determine whether advice to consume a moderate, whole food-based low-carbohydrate high-fat (LCHF) ad libitum diet (CarbCount program) can produce and maintain equal remission rates of type 2 diabetes (T2D) as a nutritionally complete very-low-calorie formula diet followed by a energy-restrictive (i.e., calorie counting) diet (DiRECT principles). Within the principles of each approach, the dietary goals and change will be adjusted according to individual needs/capabilities conducive to long-term adherence. Furthermore, the investigators aim to determine whether the rate of diet-induced remission is reflected in/can be predicted by baseline or diet-induced changes in glucose variability (e.g., time-in-range measured by continuous glucose monitoring) and other factors such as anthropometric changes and genetic susceptibility. Each center will also conduct locally-lead standalone mechanistic research, including analyses of intra-abdominal/hepatic fat accumulation, adipose tissue biopsies and/or measurements of energy metabolism. Additionally, changes in medication use, nutritional status, cardiovascular disease risk, as well as adverse events, will be monitored.
HbA1c ≥48 mmol/mol (with or without medical treatment)
Less than 10 years since the diagnosis of T2D
BMI ≥27 kg/m2 (≥25 kg/m2 for Asians)
Treatment with insulin >25 IU
HbA1c concentration of 12% or more (≥108 mmol/mol)
Insulin to C-peptide ratio <0.8 (indicative of insulin deficiency)
Myocardial infarction within the previous 6 months, and severe or unstable heart failure or other severe diseases including cancer, psychiatric/eating disorders, severe depression and substance abuse
Parallel
Energy restricted diet
Other interventionNutritional complete formula diet followed by an energy restricted diet
Low carbohydrate high fat diet
Other interventionVery low-carbohydrate high-fat ketogenic diet (VLCHF) diet followed by a low-carbohydrate high-fat diet (LCHF)
Diabetes remission
Number of patients with diabetes remission, defined as no use of glucose-lowering drugs and HbA1c \<48 mmol/mol (\<6.5%) at 15 months
Diabetes remission without anti-diabetes medications
Number of patients with HbA1c \<48 and \<42 mmol/mol at 3, 9 and 15 months, both on and off anti-diabetes medication (metformin etc.)
Changes in HbA1c and fasting glucose concentrations from baseline
HbA1c and fasting glucose concentrations (treatment targets in current clinical practice) measured in fasting blood samples
Changes in fasting insulin and insulin C-peptide concentrations from baseline
Insulin and insulin C-peptide measured in fasting blood samples
Changes in estimated insulin resistance and beta cell function from baseline
The HOMA2-calculator (https://www.dtu.ox.ac.uk/homacalculator/download.php) is used to estimate insulin resistance and beta cell function based on fasting glucose and C-peptide concentrations
Rates of T2D remission dependent on polygenic risk scores for T2D
Polygenic risk scores are calculated based on the latest GWAS data for T2D, and rates of remission compared between patients with the top 20% high- and top 20% low scores, for all participants combined and the respective diets separately
Changes in ectopic fat accumulation from baseline
Body fat measured by MRI (abdominal adipose tissue distribution, hepatic-, intramuscular-, pericardial- and pancreatic fat)
Changes in liver fibrosis and steatosis from baseline
Liver fibrosis and steatosis measured by ultrasound-based transient elastography
Changes in markers of liver function from baseline
Alanine transaminase (ALT), C-reactive protein (CRP) and other markers of liver function measured in fasting blood samples
Click on the lead sponsor to view all of their trials.
University of Bergen
Lead sponsor
Karolinska Institutet
Collaborator
University of Glasgow
Collaborator
University of Copenhagen
Collaborator
Technical University of Munich
Collaborator
