Fasting-Associated Immune-metabolic Remission of Diabetes

Obesity Clinical Trial

— FAIR  

Official title:

Fasting-Associated Immune-metabolic Remission of Diabetes Type 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05295160
• Other study ID #: FAIR-EFSD
• Status: Completed
• Phase: N/A
• Start date: September 25, 2020
• Est. completion date: April 30, 2023

Study information

• Verified date: August 2023
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity
• Type 2 Diabetes Mellitus

Intervention

Behavioral:
• weight loss by very low energy diet intake which may differ in protein or carbohydrate content
The anthropometric, endocrine and metabolic status is tested before, after 7 days and after 15 kg weight loss

Locations

Country	Name	City	State
Germany	Charité Campus Benjamin Franklin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View 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. Erratum In: Diabetes Care. 2018 Apr 24;: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of fasting blood glucose < 126 mg/deciliter	Remission of type 2 diabetes defined by a concentration of a fasting blood glucose < 126 mg/deciliter without diabetes medication	3 month
Secondary	Immune-metabolic profile and programing of innate immunity	Changes of cluster of differentiation 4/cluster of differentiation antigen 45 circulating immune cells in percent of CD4+ cells measured by flow cytometry in blood.; Concentrations of TNFalpha in pg/ml, changes of Momocyte Chemoattractant Protein-1 in pg/ml.	before, after 7 days and after 3 month
Secondary	Composition of the microbiome	Percent changes in firmicutes in stool,	before, after 7 days and after 3 month