Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient, which is why the investigators aim to reform dietary recommendation to the overweight or obese patient with type 2 diabetes. This clinical study will examine the effect of a highly controlled hypo-energetic carbohydrate-reduced high-protein (CRHP) diet intervention under caloric restriction-induced body weight loss as a treatment modality in T2D. The investigators hypothesize that this intervention compared to the conventional diabetes (CD) diet with similar loss in body weight improves metabolic control and cardiovascular risk profile in T2D by:

• Reducing diurnal and postprandial glycaemia, thereby facilitating a significant reduction in HbA1c
• Reducing ectopic lipid deposits in liver, muscle and pancreas
• Improving lipid profile towards a less atherogenic profile
• Improving metabolic actions of insulin, through increased sensitivity and β-cell function
• Reducing diurnal blood pressure with no adverse effect on heart rate variability

The present study will be performed as a 6-week randomized fully controlled feeding study, which will address the effect of the hypo-energetic CRHP diet compared with the hypo-energetic CD diet with the macronutrient composition currently recommended to patients with T2D combined with a caloric restriction-induced 5-7% body weight loss on T2D. The study includes n=80 T2D patients.

Measurements include fasting blood samples every 2 weeks during the 6 weeks of the study. Additionally, larger measurement programs will be undertaken at baseline and after 6 weeks, including MRi/s for liver, pancreas and muscle fat content and visceral and subcutaneous adipose tissue; DXA scans for body composition; oral glucose tolerance tests (OGTT); continuous glucose monitoring (CGM); diurnal blood pressure and holter recording. Questionnaires of health-related quality of life, level of physical activity and satiety by visual analogue scale will be performed at baseline and week 6 as well as fecal and diurnal urine sampling.

To ensure a similar body weight loss between intervention groups as well as participants, aimed at 5-7%, caloric intake during the 6 weeks of the study will be hypo-energetic adjusted for each participant according to estimated daily total energy expenditure (TEE). A calculation requiring sex, age, weight and height will be performed to estimate resting energy expenditure (REE), which multiplied with the participant's physical activity level (PAL) will estimate TEE, and thus with an initial caloric deficit of 5% determine the caloric content in the hypo-energetic diet for each participant. Additionally, participants will be weighed twice a week and caloric content adjusted accordingly to ensure a controlled body weight loss.

It is important to recognize that the CRHP diet and the CD diet principally do not differ in the quality of carbohydrate and protein. Thus, this study is unable to address a potential benefit of changes in quality of carbohydrate; however, both diet interventions exhibit a relatively low glycemic index of maximum 55.

Until week 6 diets will be prepared and distributed from the research kitchen of the Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, to optimize compliance and adherence to the prescribed diet. Following this period and again after approximately 3 months participants will be invited to group sessions with dietician guidance on how to sustain their body weight loss and continue with their assigned diet. A follow-up visit at week 30 will include a blood sample, a spot urine sample and body weight measurement.

Inclusion Criteria:

• Type 2 diabetes with HbA1c between 48 mmol/mol and 97 mmol/mol with or without metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors
• Overweight or obesity with BMI ≥ 25 kg/m2 and desired weight loss
• Non-smokers for > 1 year
• Willingness to abstain from alcohol for 6 weeks
• Hemoglobin > 7 mmol/L for men and > 6 mmol/L for women
• Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2

Exclusion Criteria:

• Critical illness as evaluated by the principal investigator
• Systemic corticosteroid treatment, e.g. prednisolone
• Reported or journalized severe food allergy or intolerance
• Reported or journalized severe gut disease e.g. Crohn's disease, Coeliac disease etc.
• Reported or journalized alcohol dependence syndrome
• Injectable diabetes medication, including insulin and GLP-1 analogues
• Sulfonylureas (SUs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, unless discontinuation is possible, in which case a 2-month wash-out is mandatory
• Repeated fasting plasma glucose > 13.3 mmol/L
• Urine albumin / creatinine ratio > 300 mg/g
• Lactation, pregnancy or planning of pregnancy during the study
• Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the principal investigator
• Presently participating in other clinical trials

Individual participant data (IPD) may be shared by request to the corresponding author in accordance with the Danish Data Protection Agency.