Fasting-Associated Immune-metabolic Remission of Diabetes

People with a body mass index above 28 kg/m² and an onset of type 2 diabetes within the last 4 years had a remission (HbA1c \<6.5% without medication) of diabetes in over 80% upon weight loss of 15 kg. Longer duration of diabetes reduced the chance of remission. The investigators will test whether there is a difference in remission upon weight loss of 15 kg using formula low calorie diets between subjects with a diabetes duration of \<4 years vs. \>8 years and oral treatment as primary end points. The immune metabolic programming of circulating monocytes will be investigated in detail regarding trained innate immunity and the endocrine responses will be determined using meal challenge tests.

A remission of type 2 diabetes can be achieved in over 80% of people with a diagnosis within the last 4 years and overweight or obesity by weight loss of 15 kg. The mechanisms involve an improvement of insulin sensitivity and thereby insulin requirements and a regain of the function of insulin secreting beta cells. Longer duration of type 2 diabetes appears to impair the capacity of beta cell to regenerate. At present it is not possibe to predict success of the weight loss at an early time point. The investigators therefore aim to identify early markers of responders. It is unclear how the weight loss induces the remission in responders. Immune cells are known to contribute to insulin resistance by regulating adipose tissue function and hepatic and skeletal muscle metabolism by releasing cytokines. The inborn immune system is known to adapt to external stimuli by the process of trained immunity and is thought to contribute to insulin resistance and the dysfunction of beta-cells. The investigation will analyze the programming state of innate immune cells in detail in the course of diabetes remission. In addition, islet hormone responses to challenge tests will be performed to assess their function in detail.