Adipose Tissue Imaging in Type 2 Diabetes

NCT ID: NCT02528695

Last Updated: 2017-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2017-01-31

Brief Summary

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The metabolic function of different white adipose tissue depots in the body and its role in the development of type 2 diabetes (T2D) remains unclear. Several studies have used fluor-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) to image the metabolic activity of different adipose tissues in lean and obese healthy subjects and in patients with T2D with or without euglycaemic hyperinsulinemic clamping, describing differences in metabolic activity of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and gluteal-femoral adipose tissue (GFAT). Recently, FDG PET/CT showed high glucose uptake in VAT and SAT under unintentional hypoglycaemic conditions in a non-diabetic patient. Evaluation of potential differences in FDG uptake in white adipose tissue between healthy volunteers and T2D patients and between VAT, SAT and GFAT in these subjects under hyperinsulinemic hypoglycaemic conditions would be of great value in further exploring the pathogenesis of insulin resistance in T2D.

Detailed Description

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Type 2 diabetes has become a worldwide epidemic with a prevalence of approximately 700,000 patients and an annual incidence of 70,000 in the Netherlands. The development of T2D depends on both genetic and nutritional factors and is characterized by insufficient insulin secretion by the pancreatic beta-cells and insulin resistance in liver, skeletal muscle and white adipose tissue. Insulin resistance often precedes beta-cell loss and is associated with central obesity, high blood pressure, hyperinsulinemia and dyslipidemia, all of which may lead to microvascular and cardiovascular complications.

White adipose tissue is increasingly considered a key metabolic organ in the development of insulin resistance. Especially the distribution of adipose tissue in the body is important. Indeed, visceral adipose tissue is a risk factor for coronary heart disease, certain cancers and T2D and associated with an increased cardiovascular and all-cause mortality, whereas excess of subcutaneous adipose tissue is not. There are distinct differences in the functional and hormonal characteristics of VAT and SAT, which may explain part of the mechanisms underlying the development of insulin resistance.

A more complete understanding of the molecular mechanisms that lead to T2D will enable the identification of individuals at highest risk, which could lead to more targeted prevention and pharmacological therapy.

FDG PET/CT is an established tomographic technique to image glucose metabolism with validated applications in oncology, infectious and inflammatory diseases, brain metabolism and cardiac viability. Several studies exploring the usefulness of FDG PET in imaging glucose metabolism in white adipose tissue reported lower overall glucose uptake in obese than in lean subjects. In both subject groups, glucose uptake was higher in VAT than in SAT. Glucose uptake in VAT and SAT was inversely related to insulin resistance, but uptake in GFAT was not. There are only few studies analyzing glucose uptake in patients with T2D with FDG PET/CT. In one study the impact of abdominal obesity and newly diagnosed T2D on insulin action in adipose tissue was evaluated, suggesting an excess of SAT to provide a sink for glucose, and thereby resulting in a compensatory decrease in insulin resistance. More research is needed to demonstrate the differences in glucose uptake in various adipose tissue depots in patients with T2D and correlate it with insulin resistance.

In order to keep glucose at a constant level during the FDG PET examination, usually a hyperinsulinemic euglycaemic glucose clamp is performed before scanning. Recently, a case-report was published describing an FDG PET/CT during an iatrogenic hypoglycemic state in a non-diabetic patient, which demonstrated remarkably increased glucose uptake in VAT and SAT. Based on this observation we hypothesize that glucose uptake during a hypoglycaemic state will be more pronounced in various adipose tissue depots. To our knowledge, this has not been performed in healthy volunteers or in patients with T2D. A controlled hypoglycemic state may be achieved by a hyperinsulinemic hypoglycaemic clamp, which has been used in several clinical studies. A demonstration of differences in FDG uptake in white adipose tissue between healthy volunteers and T2D patients and between VAT, SAT and GFAT under hypoglycaemic conditions would provide more insight in the glucose metabolism of adipose tissue and contribute to our understanding of insulin resistance in T2D. Even more importantly, this imaging technique might help to better characterise patients with T2D or patients at risk to develop T2D, and may thereby help to increase our understanding of the pathophysiology of T2D and the metabolic syndrome, which could lead to more targeted prevention in patients at risk and to personalised pharmacological therapy after the onset of clinically overt disease.

Conditions

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Diabetes Mellitus Type 2

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Healthy euglycemic clamp

In 5 healthy volunteers an 18F-FDG PET/CT will be performed during an euglycemic clamp

Group Type ACTIVE_COMPARATOR

18F-FDG PET/CT

Intervention Type RADIATION

18F-FDG PET/CT

euglycemic clamp

Intervention Type DEVICE

euglycemic clamp

healthy hypoglycemic clamp

In 5 healthy volunteers an 18F-FDG PET/CT will be performed during a hypoglycemic clamp

Group Type ACTIVE_COMPARATOR

18F-FDG PET/CT

Intervention Type RADIATION

18F-FDG PET/CT

hypoglycemic clamp

Intervention Type DEVICE

hypoglycemic clamp

Type 2 diabetes hypoglycemic clamp

In 5 type 2 diabetes patients, an 18F-FDG PET/CT will be performed during a hypoglycemic clamp

Group Type EXPERIMENTAL

18F-FDG PET/CT

Intervention Type RADIATION

18F-FDG PET/CT

hypoglycemic clamp

Intervention Type DEVICE

hypoglycemic clamp

Interventions

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18F-FDG PET/CT

18F-FDG PET/CT

Intervention Type RADIATION

euglycemic clamp

euglycemic clamp

Intervention Type DEVICE

hypoglycemic clamp

hypoglycemic clamp

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age \> 18 years
* BMI 27-40

For healthy volunteers:

* Fasting blood glucose \< 6.1 mmol/L
* HbA1c \< 42 mmol/mol (6%)

For T2D patients:

* Clinical overt Type 2 Diabetes
* on a glucose-lowering diet or on oral glucose-lowering medication
* T2D stable and under control for minimal 2 years
* HbA1c \< 75 mmol/mol (9%)

Exclusion Criteria

* Renal dysfunction
* Overt symptomatic neuropathy or proliferative retinopathy
* A history of cardiovascular disease complications (myocardial infarction, stroke, peripheral artery disease)
* Pregnancy or lactating
* Using subcutaneous insulin
* Incapability to provide informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Gotthardt, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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RadboudUMC

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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NL44098.091.13

Identifier Type: -

Identifier Source: org_study_id

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