Development of minimally invasive methodology for diabetyping to personalise treatment to realise remission and reversal of type 2 diabetes.

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.

The main objective of the 2DIAREM study is to develop minimally invasive
alternatives of diabetyping. Two alternative sampling methods will be
evaluated, capillary sampling 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, we aim to develop and evaluate the minimally invasive diabetyping
technology with algorithms based on capillary sampling and multi-day CGM upon a
standardized snack or multi-day CGM only under real-world conditions.

This research takes a total of 20 days. The study consists of several clinical
visits and a home measurement.
Participants are asked to follow their regular lifestyle as much as possible in
between. After 3 to 5 days, participants undergo an OGTT in the clinic. On day
8, participants are asked to consume the standardized snack (Snelle Jelle) at
home after an overnight fast and perform finger pricks. On day 10, the first
sensor expires and the participant applies a new sensor at home (the
participant receives an extensive manual and oral explanation for this). On day
17, 18 or 19, the participant will come to the clinic after an overnight fast
to consume the standardized snack again with the associated blood tests and the
sensor will be removed by an investigator.

During the 14 days of monitoring, participants are asked to undergo one OGTT
and consume a standardized snack (Snelle Jelle) twice after an overnight fast.
In between, the participants are asked to follow their usual lifestyle as much
as possible.

The burden of this study consist of application and removal of the glucose
monitor system, one OGTT and two standardized snacks. 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 wellbeing and health status of the study participants. Benefits
include that data collected through the technologies (in a less invasive way)
may be used to predict OGTT indices and diabetypes to guide personalized
lifestyle interventions for T2D patients.