Short summary

DD2 is developing a novel approach for phenotyping patients with type 2 diabetes (T2D) using the homeostasis model of assessment version 2 (HOMA2). Diabetes phenotyping is proposed as a diagnostic tool in individualizing type 2 diabetes treatment. However, the effect of day-to-day variation, glucose-lowering medication and long term follow-up on the phenotyping has not been evaluated.

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Rationale

Introduction

DD2 (Center for strategic research in type 2 diabetes), journalnumber S-20100082 is developing a novel approach for phenotyping patients with type 2 diabetes (T2D) using the homeostasis model of assessment version 2 (HOMA2)[1]. This classification is also used in the IDA study ("Specialist supervised Individualized multifactorial treatment of new clinically diagnosed type 2 diabetes in general practice (IDA)")[2]. In the study this phenotyping is used to generate an individualized treatment algorithm for T2D. Reproducibility and the effect of glucose-lowering medication of this novel classification has not previous been evaluated.

The coefficient of variation (CV) for HOMAB and HOMA-IR (or HOMAS) of the original HOMA has been established to be 32% for HOMAB and 31% for HOMA-IR in the original studies by Matthews et al.[3] Another study found CV of 19,2% for HOMAS (1/HOMA-IR)[4]. However the CV of HOMA2 has not been reported and CV in the low and high range of HOMA2B and HOMA2S are not known specific - a matter of relevance as the cut off for the phenotypes are located in these areas. The effect of medication on HOMA2 can be modeled [5] but the specific effect on the phenotype assessment is unclear. We have previously reevaluated HOMA2 and the phenotype classification in 36 patients. The reevaluation was done up to 6 years after the initial classification and was performed after 1 week discontinuation of glucose-lowering medication. Some differences were observed. Whether the differences were due to changes in insulin sensitivity and beta cell function over time or difference in preceding medication cannot be established.

The DD2 study is a cohort study on newly diagnosed type 2 diabetes with aim of improving the treatment of type 2 diabetes and to monitor type 2 diabetes through a database and a biobank in conjuctions with the danish registries. Furthermore, DD2 has the aim of forming the basis of other studies on type 2 diabetes (as this current study). Therefore the information for participants specifically informs the patient on this subject: "By saying YES to participation you accept: that DD2 can contact you about new diabetes projects, when these have been approved by the committee of ethics. To participate is voluntarily."

In the DD2-study the blood samples used for phenotype characterization can potentially be stored at room temperature for 8 hours before centrifugation. Handling of the samples might have some effect on the phenotype classification.

Aim

1. To estimate the day-to-day variation of the classification of type 2 diabetes phenotypes

2. To estimate the effect of glucose-lowering medication on the classification of type 2 diabetes phenotypes

3. To estimate how the classification changes after 4 and 8 years

4. To evaluate the potential effect of sample handling and shipment in DD2 on the phenotypes

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Description of the cohort

Inclusion criteria

1) Diagnose of clinical type 2 diabetes within 2 years

2) Currently taking glucose-lowering mediation

Exclusion criteria

New significant disease or significant chronic disease which would hamper the safety of drug discontinuation according to medical assessment by a medical doctor.

Data and biological material

Blood, interview data, medical history and clinical measurements

Collaborating researchers and departments

Steno Diabetes Center Odense

• PhD Kurt Højlund