Phenotypic and Genotypic Characterization of Patients With Dysmetabolism in Greenland

Overview

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

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.

Interventions

• 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 re
• 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).

Primary outcome measures

• Number of participants with MODY diabetes and their complication status [Time frame: Blood drawn at inclusion. Results for participants ready after approximately 6 months.]
• Number of participants with diabetic complication [Time frame: Types and number of complications are available at inclusion. No follow-up screenings for complications are performed.]
• Number of participants with obstructive sleep apnea [Time frame: 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 (3)

• CPAP compliance in Greenlandic patients [Time frame: 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). [Time frame: 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). [Time frame: The questionnaire is answered at inclusion and 6 months after.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Greenland · 1 center

• Steno Diabetes Center Greenland, Queen Ingrids Hospital — Nuuk

Identifiers

NCT: NCT06264427 · KVUG - 2022 - 10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗