Fasting-Associated Immune-metabolic Remission of Diabetes

NCT ID: NCT05295160

Last Updated: 2023-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-25
• Study Completion Date: 2023-04-30

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.

Conditions

Type 2 Diabetes Mellitus; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

type 2 diabetes - less than 4 years duration

Patients with a duration of less than 4 years since diagnosis of type 2 diabetes, BMI \> 28 kg/m², non-insulin treated who agree to loose 15 kg body weight by eating a very low calorie formula diet of 800 kcal/day for men and 600 kcal/day for women. The duration of the diet is until the weight loss is achieved.

Group Type: OTHER

weight loss by very low energy diet intake which may differ in protein or carbohydrate content

Intervention Type: BEHAVIORAL

The anthropometric, endocrine and metabolic status is tested before, after 7 days and after 15 kg weight loss

type 2 diabetes - more than 8 years

Patients with a duration of more than 8 years since diagnosis of type 2 diabetes, BMI \> 28 kg/m², non-insulin treated who agree to loose 15 kg body weight by eating a very low calorie formula diet of 800 kcal/day for men and 600 kcal/day for women. The duration of the diet is until the weight loss is achieved.

Group Type: OTHER

weight loss by very low energy diet intake which may differ in protein or carbohydrate content

Intervention Type: BEHAVIORAL

The anthropometric, endocrine and metabolic status is tested before, after 7 days and after 15 kg weight loss

Interventions

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

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Andreas F. H. Pfeiffer

Senior Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas FH Pfeiffer, MD

Role: STUDY_DIRECTOR

Universitätsmedizin Berlin CBF

Locations

Charité Campus Benjamin Franklin

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 29221645 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27002059 (View on PubMed)

Other Identifiers

FAIR-EFSD

Identifier Type: -

Identifier Source: org_study_id