The Role of Autoantibodies Against G-protein Coupled Receptors in Obesity

The purpose of this study is to explore if GPCR-autoantibodies:

1. are pressent in people living with obesity, and are associated with degree of obesity
2. if it is associated with obesity related diseases

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Obesity & Overweight; Obesity Type 2 Diabetes Mellitus; Obesity and Obesity-related Medical Conditions

Detailed Description

The present study aims to investigate the role of GLP1-R autoantibodies in a large, deeply phenotyped obesity cohort. In an unblinded exploratory analysis, GLP1-R, GIP-R and ghrelin-R autoantibody levels will be measured using proprietary assay. The central hypothesis is that the presence and concentration of these autoantibodies is positively associated with the degree of obesity. Secondary we hypothesize that the presence and concentration of GLP1-R or GIP-R autoantibodies are associated with the presence of insulin resistance and prediabetes. As an exploratory approach we hypothesize that the presence and concentration of GLP1-R, GIP-R or ghrelin-R autoantibodies is associated with eating behavior as assessed by the validated questionnaire Adult Eating Behavior Questionnaire.

At present, it is unknown whether these autoantibodies exert an inhibitory, neutral, or agonistic effect on GLP1R, GIP-R or ghrelin-R signaling. Furthermore, it remains unclear whether individuals with obesity and diabetes-conditions associated with impaired GLP-1 signaling-exhibit a higher prevalence of GLP1R autoantibodies, or whether these autoantibodies differ functionally between diabetic and non-diabetic individuals. Addressing these questions may help explain interindividual variability in weight loss responses and uncover a novel immuno-endocrine mechanism relevant to obesity and metabolic disease.

The project will take advantage of the South Danish Obesity Initiative (SDOI) cohort. This is an ongoing clinical initiative offering screening of a broad panel of obesity related diseases to individuals with BMI above 30 kg/m² and age between 18 and 60 years. People are referred from their general practitioners or from hospital departments and undergo screening for diabetes, dyslipidemia, obstructive sleep apnea, metabolic-associated steatohepatitis and hypertension. In addition, the participants answer questionnaires including the Adult Eating Behavior Questionnaire. A Danish translation of this questionnaire has been validated, and the questionnaire allows evaluation of eating habits (Kolin M.E.I. et al, 2025. DOI:10.3390/nu17243824). A cohort of people with BMI 18.5 to 30 kg/m² has been assessed with an identical screening program with the purpose of serving as a control group. Only participants who gave informed consent to use their data for research purposes are included in this study. The SDOI screening protocol and initial results have previously been published (Juhl C.B. et al 2024. DOI:10.2147/DMSO.S456028).

In the present study we will include 160 participants from the SDOI cohort, of which 120 will be individuals living with obesity. Where 40 participants will have a BMI above 50 kg/m², 40 will have a BMI 40-50 kg/m², 40 will have a BMI 30-40 kg/m². The remaining 40 participants will be from the control cohort (BMI 18.5 to 25 kg/m²). The groups will be matched on sex and age (within 2 years). Individuals with type 1 diabetes and individuals treated with GLP-1RAs for any indication and individuals who have previously undergone bariatric surgery will not be included in the trial.

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Tobias M Windedal, MD; Phone Number: 45 42957945; Email: tobias.midtvedt.windedal@rsyd.dk
• Study Contact Backup: Name: Claus B Juhl, Professor, MD, PhD; Phone Number: 45 79183120; Email: claus.bogh.juhl@rsyd.dk

Study Locations

• Denmark
  • Region Syddanmark
    • Esbjerg, Region Syddanmark, Denmark, 6700
      • University Hospital of Southern Denmark, Esbjerg
      • Contact: Anitta Ø Johansen, Chief consultant; Phone Number: +45 + 21338607; Email: anitta.oehlenschlaeger@rsyd.dk
      • Principal Investigator: Claus B Juhl, Professor, MD, PhD
      • Sub-Investigator: Tobias M Windedal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The South Danish Obesity Initiative (SDOI) cohort. This is an ongoing clinical initiative offering screening of a broad panel of obesity related diseases to individuals with BMI above 30 kg/m² and age between 18 and 60 years. People are referred from their general practitioners or from hospital departments and undergo screening for diabetes, dyslipidemia, obstructive sleep apnea, metabolic associated steatohepatitis and hypertension. In addition, a cohort of people with BMI 18.5 to 30 kg/m² has been assessed with an identical screening program with the purpose of serving as a control group. Only participants who gave informed consent to use their data for research purposes are included in this study.

Description

Inclusion Criteria:

• Inhabitant in the Region of Southern Denmark
• BMI above 30kg/m2
• age between 18 and 60 years.

Exclusion Criteria:

• individuals previously treated with GLP-1RA medication for any indication
• Individuals who have previously undergone bariatric surgery
• Individuals with type 1 diabetes

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

The South Danish Obesity Initiative (SDOI); The project will take advantage of the South Danish Obesity Initiative (SDOI) cohort. This is an ongoing clinical initiative, offering screening of a broad panel of obesity related diseases to individuals with BMI above 30 kg/m² and age between 18 and 60 years. People are referred from their general practitioners or from hospital departments and undergo screening for diabetes, dyslipidemia, obstructive sleep apnea, metabolic-associated steatohepatitis and hypertension. In addition, the participants answer questionnaires. A cohort of people with BMI 18.5 to 30 kg/m² has been assessed with an identical screening program with the purpose of serving as a control group. Only participants who gave informed consent to use their data for research purposes are included in this study. The study protocol and initial results have previously been published (Juhl C.B, et al 2024.DOI: 10.2147/DMSO.S456028).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring the pressence and role of GPCR-autoantibodies in obesity	explore the pressence of GPCR-autoantibodies in people living with obesity, and if there is any association with the degree of obesity	At the time of enrolement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring the association between GPCR-autoantibodies and obesity related diseases	explore if the pressence of GPCR-autoantibodies is associated with obesity related diseases (pre-diabetes, type 2 diabetes and metabolic syndrome) in people living with obesity	At the time of enrolment

Collaborators and Investigators

• Sponsor: Claus Bogh Juhl
• Investigators: Principal Investigator: Claus B Juhl, Professor, MD, PhD, University Hospital of Southern Denmark, Esbjerg

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; obesity-related medical conditions; GPCR- autoantibodies
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: 26/14976

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: GDPR regulations and patient anonymity

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No