Development of Minimally Invasive Methodology for Diabetyping to Personalise Treatment to Realise Remission and Reversal of Type 2 Diabetes (2DIAREM)

Rationale: Lifestyle changes in diet and exercise can reverse type 2 diabetes (T2D), also referred to as T2D remission. Although combined lifestyle interventions for T2D remission are promising, not all persons react similarly to such 'one-size-fits-all' interventions. Research has shown that as a result of differences in T2D pathophysiology between individuals, different subgroups of T2D can be identified, that differ in which diet is most beneficial in the recovery of pancreatic beta-cell function. TNO and partners work on the development of the Diabetyping Lifestyle Intervention (DLI) for T2D subtypes that tailors the combined lifestyle intervention based on organ dysfunction (liver, muscle and/or pancreatic beta cell function) by using the Oral Glucose Tolerance Test (OGTT). Current diabetyping is invasive, needs to take place in a clinical setting, and therefore is not suited for scaling to application in the large T2D population of more than 1 million people. Therefore, less invasive, scalable alternatives are warranted.

Objective: The main objective of the 2DIAREM study is to develop minimally invasive alternatives of diabetyping. Two alternative sampling methods will be evaluated, finger pricks and continuous glucose monitoring (CGM). Data collected through these technologies may be used to predict OGTT indices and diabetypes to guide personalized lifestyle interventions for T2D patients. Furthermore, the investigators aim to develop and evaluate the minimally invasive diabetyping technology with algorithms based on finger prick sampling and multi-day CGM upon a standardized snack or multi-day CGM only under real-world conditions.

Study design: The study will be an observational study, lasting 20 days and consisting of three mornings with measurements.

Study population: A heterogenous group of people with overweight/(pre)diabetes type 2. The investigators aim for equal distribution among overweight/prediabetes, mild diabetes, and severe diabetes in the study population.

Intervention (if applicable): During the 20 days of monitoring participants are asked to undergo one OGTT and consume two times a standardized snack (Snelle Jelle (naturel 65 gram)) after an overnight fast. In between participants are asked to follow their usual lifestyle.

Main study parameters/endpoints: Continuously measured subcutaneous glucose, as well as, glucose and insulin, and c-peptide collected via capillary sampling for the development of algorithms predicting the different diabetypes and the underlying indices based on venous blood glucose and insulin.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden of this study consists of the application and removal of the continuous glucose monitor device, and the consumption of a sweet beverage (OGTT) and two standardized snacks and undergoing several capillary blood draws. The risks associated with participation can be considered negligible, and are mainly associated with the glucose sensor and the OGTT. The glucose sensor provides a small risk of adverse events including skin irritation, skin infection, and skin colouring. The OGTT poses a small risk of hypo- or hyperglycaemia and can lead to nausea. However, experienced medical professionals are present at the clinic and will closely monitor well-being and health status of the study participants. Benefits include that data collected through the technologies may be used to predict OGTT indices and diabetypes much less invasively and scalable to guide personalized lifestyle interventions for T2D patients.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes

• Study Type: Observational
• Enrollment (Estimated): 57

Contacts and Locations

• Study Contact: Name: Kristel Kamstra; Phone Number: +31611873786; Email: kristel.kamstra@tno.nl

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • Reinier Haga
    • Contact: Frans van der Horst
    • Contact: Kristel Kamstra

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study population consists of people with overweight/prediabetes, mild diabetes and severe diabetes, as diagnosed by BMI, disease duration, medication use and CVD history. The three subpopulations are selected to ensure representative variability in OGTT response and diabetes subtypes.

Description

Inclusion Criteria:

• Diagnosed with (pre)diabetes type 2;

  • BMI ≥27 kg/m2, including a heterogenous group of people/with overweight/prediabetes (without glucose lowering medication), and/or type 2 diabetes with or without glucose lowering medication.
• Aged 40 years or older
• Able and willing to sign the informed consent form
• Willing to comply with all study procedures

Exclusion Criteria:

• Type 1 diabetes
• Latent Autoimmune Diabetes (LADA)
• Skin allergy, eczema or known sensitivity for adhesives
• History of bariatric weight loss surgery
• Planned (bariatric) surgery during the 3 weeks monitoring period with the CGM
• Active cancer or chemotherapy or radiation within 2 years prior to participation
• A condition that would need an MRI during the 3 weeks monitoring period with the CGM
• Planned holiday during the 3 week GCM monitoring period
• (Night)shiftworkers
• Pregnancy and lactation
• Chronic medical condition, treatment, or medication other than diabetes that may affect glucose metabolism (HIV diagnosis, use of steroids or immunosuppressive drugs, etc.)
• 4 or more alcoholic drinks per day on a regular basis or use of recreational drugs

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose values (mmol/l)	Measured in venous blood, capillary blood and interstitial fluid (via the CGM) before and during the OGTT	In-study at day 3 and day 17 (venous and capillary) during 20 days with CGM
Insulin (mIU/l)	Measured in venous blood and capillary blood before and during the OGTT	In-study at day 3 and day 17 (venous and capillary)
c-peptide (nmol/l)	Measured in venous blood and capillary blood before and during the OGTT	In-study at day 3 and day 17 (venous and capillary)
Diabetyping	Development of algorithms predicting the different diabetypes and the underlying indices with minimally invasive data collection (e.g. capillary blood sampling with sample tube/dry blood spot and CGM)	End of study (after 20 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose values (mmol/l)	Measured in capillary blood, venous and interstitial fluid (via the CGM) before and during the standardized snack	In-study at day 8 (capillary) and day 17 (venous and capillary) during 20 days with CGM
Insulin (mIU/l)	Measured in capillary blood, venous and interstitial fluid (via the CGM) before and during the standardized snack	In-study at day 8 (capillary) and day 17 (venous and capillary)
c-peptide (nmol/l)	Measured in capillary blood, venous and interstitial fluid (via the CGM) before and during the standardized snack	In-study at day 8 (capillary) and day 17 (venous and capillary)
Diabetyping	Assess the agreement between diabetyping based on a standardized snack as compared to the OGTT	End of study (after 20 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported experiences with capillary blood sampling in an at home setting	Via a self composed questionnaire with open and closed questions	End of study (day 19)

Collaborators and Investigators

• Sponsor: TNO

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NL83666.028.23

Drug and device information, study documents

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