Energy Balance Following Islet Transplantation

Summary

Islet transplantation may be appropriate in up to 10% of adults with Type 1 diabetes who suffer repeated episodes of hypoglycaemia with severely impaired awareness of hypoglycaemia (IAH) (1). Our Scotland-wide islet transplant programme performed its first transplant in February 2011 and 30 islet transplants have followed in 18 recipients. Following islet transplantation we have observed improved glycaemic control in all subjects. When metabolic control is improved with exogenous insulin, weight gain is common (2). In our transplant recipients significant reductions in bodyweight and fat mass with no significant reduction in total caloric intake pre- versus post-transplantation has been observed. We hypothesise that energy expenditure is increased post-transplantation leading to weight loss and diminished fat mass. The mechanisms that may be implicated include increased activity energy expenditure, increased resting energy expenditure (REE) and, or, increased post-prandial thermogenesis (PPT= the energy expended after a meal) secondary to increased portal circulation of insulin being partially or fully restored, and diminished circulating systemic insulin concentrations with a decreased propensity for storing fat. The aim of this study is to understand the mechanism of weight loss and body compositional changes by detailed examination of energy intake and energy expenditure in transplant recipients along with control subjects listed for insulin-pump therapy and glucose tolerant controls. These detailed studies are lacking in islet transplantation and are important as they will reveal how physiology is altered post-transplantation, if peripheral hyperinsulinaemia (insulin-pump subjects and pre-transplant subjects) negatively affects energy expenditure and how quantitative measures such as activity energy expenditure, diet and quality-of-life measures such as fear of hypoglycaemia alter post-transplant. This will lead to the improved management of patients with hypoglycaemia and IAH.

Conditions

• Type 1 Diabetes

Interventions

DEVICE

Accelerometer

Attach a monitor to participants thigh to measure their physical activity for 7 days. The monitor is called the Activpal Micro.

OTHER

Anthropomentry

Take skinfold measurements of participants using Harpenden skinfold calipers.

PROCEDURE

Blood tests

Taking standard clinical blood tests to measure HbA1c, Glucose, FBC, U\&E's, LFT's, Coagulation Screen, Lipid Profile, Thyroid Function, and Tacrolimus for transplant patients.

DEVICE

BODPOD

Measure body composition using a BODPOD machine. This uses Air displacement plethysmography.

PROCEDURE

MRI (Magnetic Resonance Imaging)

MRI Scans of abdomen, particularly the livers of islet transplant and insulin pump patients.

OTHER

Food Diary

Participants will keep a 7 day weighed food diary.

DEVICE

CGMS (Continuous Glucose Monitoring System)

Participants will wear a CGMS for 7 days to measure their glucose control and pattern over a 7 day period.

OTHER

Questionnaire and Hypo Score

Participants with Type 1 Diabetes will fill in 3 short questionnaires about their Diabetes.

PROCEDURE

Mixed Meal Tolerance Test (MMTT)

The patients will under go a test which involves taking 30 minute glucose and C-peptide levels (blood test from a cannula) for 3 hours. They will consume 150ml of a mixed meal supplement drink "Fortisip Compact" at the start of the 3 hours, after having no morning insulin, breakfast and not eating anything from midnight the night before.

PROCEDURE

Indirect Calorimetry

During the Meal Tolerance Test, the patients will be resting on a bed in the research facility and breathing normally into a clear plastic hood. The machine connected to the hood (GEM) will analyse their resting energy expenditure from the gases expired in their breath. They will have the hood on for 2 hours.

DRUG

Doubly Labelled Water

The Doubly Labelled water will be prescribed for the participants and they will drink their 100ml dose of the stable isotope. Dose depends on the eight of the participant. The participant will then collect urine samples at home on day 5, 10 and 14 after drinking the water. They will store them in the freezer until they can bring them back to us.

DRUG

Hepatic Mitochondrial Oxidation breath test

Participants will be given a calculated amount of the stable isotope C-Octanoate, which will be delivered in a water solution. They will then be asked to breath down a small tube into a clear plastic collection bag 10 times over 2 hours.

Sponsors & Collaborators

• NHS Lothian

  collaborator OTHER_GOV

• University of Edinburgh

  lead OTHER

Principal Investigators

• Shareen Forbes, MD · NHS Lothian

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2019-10-23

Completion

2019-10-23

Countries

• United Kingdom

Study Locations