Clinical trial NCT05295160: Fasting-Associated Immune-metabolic Remission of Diabetes
Official title: Fasting-Associated Immune-metabolic Remission of Diabetes Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Obesity
Keywords: type 2 diabetes mellitus in obese
insulin secretion
innate immunity
monocyte programming
remission of type 2 diabetes
weight loss
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Obese people with type 2 diabetes with a duration of less then 4 years will be compared with people with type 2 diabetes for more than 8 years regarding their capability to achieve remission of type 2 diabetes in response to a weight loss of 15kg achived using very low calorie intake
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes diagnosed less than 4 or over 8 years, before study,
* BMI \> 28 kg/m²,
* willingness to follow weight loss diet,

Exclusion Criteria:

* consuming disease,
* intolerance for very low calorie formula diet,
* known severe hepatic disease or liver cirrhosis,
* type 1 diabetes,
* severe disease of kidney or heart,
* advanced diabetic retinopathy,
* intake of glucocorticoids,
* drug or alcohol abuse,
* weight loss of \>5 kg in the last 3 month,
* eating disorder

Primary outcomes:
measure: Concentration of fasting blood glucose < 126 mg/deciliter
timeFrame: 3 month
Secondary outcomes:
measure: Immune-metabolic profile and programing of innate immunity
timeFrame: before, after 7 days and after 3 month
measure: Composition of the microbiome
timeFrame: before, after 7 days and after 3 month
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
Study officials:
affiliation: Universitätsmedizin Berlin CBF
name: Andreas FH Pfeiffer, MD
role: STUDY_DIRECTOR
References:
citation: Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5.
citation: Steven S, Hollingsworth KG, Al-Mrabeh A, Avery L, Aribisala B, Caslake M, Taylor R. Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders. Diabetes Care. 2016 May;39(5):808-15. doi: 10.2337/dc15-1942. Epub 2016 Mar 21.