Digital, Blended Lifestyle Intervention for Type 2 Diabetes Remission

410 Dutch type 2 diabetes patients will be randomized using a 5:1 ratio to intervention group versus control, to a lifestyle intervention program given via a mobile application and digital platform. Active participants will undergo diabetyping, where blood glucose and c-peptide responses to a glucose challenge are measured, and be recommended to follow a calorie-restricted (minimum 500 kcal deficit) low-carbohydrate, or restricted carbohydrate (120g) Mediterranean diet and customized exercise program for a period of 24 weeks. Individuals will then be followed for a period of 2 years following the intervention.

Patients will partake in a 24-week intervention followed by a two-year follow-up period. The intervention will consist of diabetic phenotyping (diabetyping), and a personalized app-based lifestyle intervention, done in conjunction with usual care, the so-called blended care model. Individuals will be allocated to either a high (unsaturated) fat, low-carbohydrate Mediterranean (50 g), or the Mediterranean with limited carbohydrates (120 g) diet based on their diabetype, insulin use, and personal preference. This will be given in conjunction with physical activity program, which will focus more on aerobic activity or resistance training depending on diabetype. All participants will be provided with additional coaching to support behavioral change, which will include aspects of diet, physical activity but also aspects of mindfulness, and emotion regulation. The participants will be assessed at screening, before the start of the maintenance phase, and at follow-ups one, two, and three. Control patients will follow the usual care and will also be followed up, following the same schedule. The treatment is further clarified below:

Prior to commencing the study, participants in the active intervention group will receive a kit containing all the necessary products (i.e. wearable, smart scale, and glucose monitor), information, and instructions (where applicable) for participating in the study. Moreover, they will be carefully informed about the types of personalisations available to them. The participants will have either a whole food type diet or a low carbohydrate diet recommended to them based on their metabolic profiles. In addition, they will also have specific types of exercise recommended to them. Participants' treating physicians and coaches will be informed about their choices, and will receive supporting medication adjustment documents, based on those made in previous studies. It will remain the responsibility of the treating physicians to adjust any medications the participants are receiving.

The control group is required to meet the same criteria as the intervention group. The control group only receives health assessments (with the exception of the diabetyping), and will not receive any health intervention. They will continue to receive standard diabetes care.

Eligibility Criteria:
Inclusion Criteria:

* Diabetes: Diagnosis of T2DM without physician defined end-organ failure
* BMI: 25 to 45 kg/m²
* Age: 18 to 75 years
* Most recent HbA1c value should be greater than 6.0% (\>43 mmol/mol); if less than 6.5% (\<48 mmol/mol), individuals should still be receiving anti-diabetic medication
* Tech-savvy (patients are required to be able to fully use smartphone or tablet)
* Display interest and motivation to enroll in a digital, lifestyle intervention for diabetes

Exclusion Criteria:

* Weight loss of more than five kg or greater than 10% within the past six months
* Serious co-morbidities, for example, a severe form of chronic obstructive pulmonary disease (Gold III or IV), bariatric surgery, heart failure (classes 2-4) kidney failure, or another medically determined end-stage organ failure
* Substance abuse
* Learning difficulties limiting the participation in a digital health intervention and or limiting the comprehension of trial goals or coaching curriculum.
* Current treatment with anti-obesity drugs
* Pregnancy, consideration of pregnancy within the study period, lactation or having given birth within the previous nine months
* Hospital admission for depression
* Major psychiatric disorder (e.g., schizophrenia, bipolar disorder) or use of antipsychotic drugs.
* Currently uncontrolled or eating disorder or purging behavior
* Type 1 diabetes
* History of keto-acidosis
* Myocardial infarction, stroke, angina, or coronary insufficiency within the previous six months
* Diabetic retinopathy requiring treatment
* Creatinine \> 2.0 mg·dL-1 or \> 152.5 µmol·L-1
* Urinary albumin \> 1 g·dL-1 or \> 10 g·L-1
* Cancer requiring treatment in the past five years, with the exception of non-melanoma skin cancer
* Chronic infectious disease requiring ongoing treatment
* Other chronic diseases or conditions likely to limit lifespan to less than six years
* Severe visual impairment or other impairment preventing interaction with digital content
* Non-English or Non-Dutch speaking
* Excessive alcohol intake (acute or chronic) defined as the average consumption of three or more alcohol-containing beverages daily or consumption of more than 14 alcoholic beverages per week
* Cholelithiasis or biliary dysfunction
* Use of an insulin pump
* Participation in diabetes therapy within the preceding three years; participation in concurrent weight management or interventional research protocol,
* Untreated thyroid disease,
* Requirement of a prescribed medical diet
* A recent on-record estimated glomerular filtration rate of less than 30 mL/min per 1.732 m²
* Incapacitated patients, and thus unable to fully participate in the trial.
* uncontrolled blood pressure (SBP \> 170 mmHg and/or DBP \> 100 mmHg)
* For nutritional ketosis specifically: impaired hepatic function (Bilirubin \>2 mg·dL-1 or \>34.2 µmol·L-1, Albumin \< 3.5 g·dL-1 or \<35 g·L-1)