Phenotypic and Genotypic Characterization of Patients With Dysmetabolism in Greenland

The goal of this clinical trial is to perform a detailed description of the feno- and genotype of people living with type 2 diabetes and severe obesity who are linked to care at Steno Diabetes Center Greenland.

The main questions it aims to answer are:

• Are monogenetic diabetes variants associated with the same risk of developing late diabetic complications as other types of diabetes?
• Can genotyping and thereby personalized medicine be implemented in Greenland, and can personalized medicine lead to improved treatment?
• What is the prevalence of sleep apnea among high-risk individuals in Greenland?
• Is it possible to develop and implement a simple algorithm for the identification of sleep apnea in Greenland that can ensure treatment of severe sleep apnea?

Participants will:

• Answer WHO-5 and FOSQ-10 questionnaires regarding quality of life and functional outcomes of sleepiness
• Perform VAGUS examinations for Cardiovasculare Autonomic Neuropathy
• Clinical examination of height, weight, circumference of hip, waist and neck, Friedman tonsil and tongue score, nasal air flow, nasal septal deviation
• Blood samples for full genome sequencing

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetic Retinopathy; Obstructive Sleep Apnea; Obesity, Morbid; MODY
• Intervention / Treatment: Genetic: Whole genome sequencing; Diagnostic test: VAGUS; Diagnostic test: NightOwl; Device: CPAP

Detailed Description

The phenotypic and genotypic characteristics of dysmetabolism in the Greenlandic Inuit population are yet to be described in detail. However, the unique interaction of genetic and environmental factors in this population and its effect on disease development calls for further investigation. Therefore, we aim to examine how metabolic diseases manifest and progress distinctively in this population compared to Western populations.

The study employs whole genome sequencing, with a focus on identifying variants in the TBC1D4 gene, which is linked to muscular insulin resistance, and HNF1α, associated with MODY (Maturity-onset Diabetes of the Young) diabetes. In addition, the prevalence of Obstructive Sleep Apnea (OSA) in relation to metabolic disorders is examined. Our methodology combines genetic analysis with clinical evaluations to understand the impact of these genetic factors on disease manifestation and potential complications.

The findings will likely offer a unique perspective on the genetic influence on metabolic diseases in the Greenlandic Inuit population, highlighting the significance of novel genetic variants for disease management and prevention. The study investigates the relationship between metabolic disorders and OSA, and aims to describe how diagnosis and treatment of OSA can be introduced in an Arctic setting. This research emphasizes the need for genotype-aware treatment approaches and culturally tailored healthcare strategies, not only for the Greenlandic Inuit but also as a model for personalized medicine approaches in other populations. The insights gained here contribute to a deeper understanding of metabolic diseases, potentially influencing future global healthcare strategies.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mads Jensen, MD.; Phone Number: +299 34 46 23; Email: MMSN@peqqik.gl
• Study Contact Backup: Name: Marit Eika Jørgensen, MD. Ph.d; Phone Number: +299 34 43 24; Email: MAEJ@peqqik.gl

Study Locations

• Greenland
  • Sermersooq
    • Nuuk, Sermersooq, Greenland, 3900
      • Recruiting
      • Steno Diabetes Center Greenland, Queen Ingrids Hospital
      • Contact: Mads Mose Jensen, MD.; Phone Number: +299 34 46 23; Email: MMSN@peqqik.gl
      • Contact: Marit Eika Jørgensen, Md. Ph.d; Phone Number: 34 43 24; Email: MAEJ@peqqik.gl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Type 2 diabetes and/or morbid obesity (BMI >40)
• Over 18 years old

Exclusion Criteria:

• Does not speak either English, Danish or Greenlandic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention arm; All participants will undergo examination for genom sequencing, diabetic complications and obstructive sleep apnea. Treatment for these conditions will not be randomized, but will be offered any participant who fulfills the excision treatment criteria

Genetic: Whole genome sequencing; Screening for MODY diabetes. Diabetic treatment will be adjusted based on the participant's diabetic genotype.; Diagnostic test: VAGUS; To examine for Cardiovasculare Autonomic Neuropathy participants will be tested with the handheld Vagus device (Medicus Engineering, Aarhus, Denmark). Participants are instructed to perform three cardiovascular reflex tests (CARTs) after lying still in supine position for 5 minutes to record heart rate at rest. CARTs include supine-to-upright position, deep-breathing, and valsalva maneuver. From each CART the ratio based on the shortest and longest R-R-interval at predefined timepoints in the recording is used to assess the possibility of CAN; Diagnostic test: NightOwl; Participants will be examined for sleep apnea for 3 nights using the NightOwl (Ectosense, Belgium) device, which measuring Peripheral Arterial Tonometry (PAT) in the index finger. The results of the examination will is uploaded via the patient's smartphone to an online platform accessible to healthcare providers. Participants with signs of sleep apnea will receive a confirmatory cardiorespiratory monitoring using the Nox T3s (Noxturnal, ResMed), and the results will be compared.; Device: CPAP; Participants with an Apnea-Hypoapnea-Index above 30, or above 15 with symptoms of sleep apnea, will be offered treatment with continuous positive airway pressure (CPAP).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with MODY diabetes and their complication status	What is the proportion of patients linked to care at SDCG who have MODY diabetes, and to what degree do they suffer from micro- and macrovascular complication.	Blood drawn at inclusion. Results for participants ready after approximately 6 months.
Number of participants with diabetic complication	What is the proportion of participants with diabetes complication overall.	Types and number of complications are available at inclusion. No follow-up screenings for complications are performed.
Number of participants with obstructive sleep apnea	What proportion of participants suffer from OSA.	Home sleep testing is performed for 3 nights after inclusion. Confirmatory home sleep examinations performed one day after the initial sleep examination. In total, four days examinations time.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPAP compliance in Greenlandic patients	Is it possible to develop and implement a specialized treatment regime for obstructive sleep apnea in Greenland with similar treatment compliance when compared with other populations. CPAP compliance is evaluated through the online treatment system Airview (Resmed), where compliance is defined as minimum 4 hours use for 70% of nights in the past 90 days.	CPAP compliance is evaluated 6 months after treatment initiation.
CPAP treatment effect on quality of life measured with the World Health Organization Well-being Index (WHO-5).	The World Health Organization Well-being Index (WHO-5) questionnaire is performed at inclusion and 6 months after. The raw scores are transformed to a score between 0 and 100, where high scores indicate higher wellbeing. Scores for participants in CPAP treatment will be compared before and after treatment to examine the effect of CPAP on quality of life.	The questionnaire is answered at inclusion and 6 months after.
CPAP treatment effect on daytime sleepiness measured with the functional outcome of sleep questionnaire (FOSQ-10).	The functional outcome of sleep questionnaire (FOSQ-10) is performed at inclusion and 6 months after. A total score, with a potential value between 5-20, is calculated. Low values indicate excessive daytime sleepiness while high scores indicate no excessive daytime sleepiness. Scores for participants in CPAP treatment will be compared before and after treatment to examine the effect of CPAP on quality of life.	The questionnaire is answered at inclusion and 6 months after.

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Greenland
• Collaborators: Zealand University Hospital; University of Copenhagen
• Investigators: Principal Investigator: Marit Eika Jørgensen, Md. Phd, Steno Diabetes Center Greenland

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sleep Apnea Syndromes; Obesity; Sleep Apnea, Obstructive; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Obesity, Morbid; Diabetic Neuropathies
• Other Study ID Numbers: KVUG - 2022 - 10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be available for researcher who hold relevant approval from the Science Ethical Committee and health authorities.
• IPD Sharing Time Frame: Study protocol will be published in first quarter of 2024. Analytic code will be published in final peer reviewed articles alongside results of the study.
• IPD Sharing Access Criteria: Ethical permission from Science Ethical Committee Approval from Health Authorities, Queen Ingrids Hospital Data Sharing Agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No