Beta Cell Imaging in T1D Patients With a Different Glycemic Control (GLP1-reg)

Radboud University Medical Center

Status

Terminated

Conditions

Type 1 Diabetes Mellitus

Treatments

Radiation: gallium-68-exendin PET/CT

Study type

Observational

Funder types

Other

Identifiers

NCT03785275

NL59582.091.17

Details and patient eligibility

About

The primary aim of this study is to measure (residual) beta cell mass in type 1 diabetes (T1D) patients with stable near-normal and unstable glucose control using PET/CT imaging, to improve the understanding of the relation between beta cell mass and glycemic control in T1D.

Full description

Type 1 diabetes (T1D) is characterized by a progressive decrease in beta cell function due to an autoimmune attack on the beta cells, which will lead to a reduction in insulin secretion. Endogenous insulin secretion can be determined measuring C-peptide, which is secreted in equal amounts to insulin. The loss of insulin secretion, indicated by an immeasurable C-peptide level, will hamper glycemic control which results in increased glycated haemoglobin (HbA1c) levels. Also, hypoglycemic events can occur more frequently. Initially, the belief was that this could be explained by the loss of all pancreatic beta cells due to the autoimmune attack. However, recent literature suggests that a considerable number of beta cells can survive this attack. This could mean that certain beta cells survived, but have lost their function. The ratio of functional and non-functional residual beta cells might play an important role in the degree of glycemic control. It would therefore be of great interest to study residual beta cell mass in two types of T1D patients that differ in glycemic control. Although both types of patients receive treatment, one group of patients is characterized by a stable near-normal glucose control while the second group is characterized by an unstable glucose control. In case glycemic control mostly depends on beta cell function and less on beta cell mass, novel therapies could focus on the functional reactivation of these non-functional beta cells to restore overall beta cell function. This could especially be in favour of patients with an unstable glucose control. Beta cell mass will be determined using Ga-68-NODAGA-exendin-4 positron emission tomography (PET), which allows visualization of pancreatic beta cells as well as absolute quantification of tracer uptake, providing a measure for the pancreatic beta cell mass. The outcome of this study will lead to a better understanding of the relation between the amount of residual beta cells, beta cell function and the influence of glycemic control. This could provide new insights regarding the development of new therapies to improve beta cell function and glycemic control, which could lower disease burden and improve the patient's quality of life.

Enrollment

16 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Group 1 (stable glycemic control)

Age ≥18 years
T1D diagnosed ≥1 year at the start of the study
HbA1c <7 (<53 mmol/mol)
17≤ BMI ≤30 kg/m2
No severe hypoglycemic events in the past year and a maximum of 2 severe hypoglycemic events in their entire life.
Intact hypoglycemic awareness
Ability to sign informed consent

Group 2 (unstable glycemic control) Age ≥18 years

T1D diagnosed ≥1 year at the start of the study
HbA1c >8.5 (>69 mmol/mol)
17≤ BMI ≤30 kg/m2
Minimum of 2 severe hypoglycemic events in the past year, or an impaired awareness of hypoglycemia (subjects may comply with both criteria, but this is not a requirement)
Ability to sign informed consent

Exclusion criteria

Previous treatment (within 6 months) with synthetic Exendin (Exenatide, Byetta®) or Dipeptidyl-Peptidase IV inhibitors
Liver disease
Renal disease
Pregnancy or the wish to become pregnant within 6 months after the study
Breastfeeding
BMI <17 kg/m2 or BMI >30 kg/m2
Age <18 years
Inability to sign informed consent