Clinical trial NCT03669770: Ultrasound Classification and Grading of Lipohypertrophy and Its Impact on Glucose Variability in Type 1 Diabetes
Official title: Ultrasound Classification and Grading of Lipohypertrophy and Its Impact on Glucose Variability in Type 1 Diabetes: The TITANIC Studies.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lipohypertrophy
Type 1 Diabetes Mellitus
Keywords: Lipohypertrophy
Type 1 Diabetes Mellitus
Ultrasound
Glucose variability
Glycaemic control
Lead sponsor: King's College London
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 75
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All T1DM patients attending the diabetes clinics in GSTFT thought to have have LH and fitting the above criteria.

Brief summary: This study will use ultrasound to characterise lipohypertrophy(LH) and assess the impact of LH on glucose variability in adults with type 1 diabetes. LH is a condition that occurs with repeated exposure to insulin at injection sites, resulting in the development of subcutaneous fatty lumps that impede the absorption of insulin. LH can lead to glucose variability, increased risk of severe hypoglycaemia and diabetes distress. In the long term it can therefore lead to increased risk of diabetes complications and increased insulin costs.

Detailed description: This is an observational study using ultrasound (US) to assess and characterise lipohypertrophy (LH) with a sub-study to assess the impact of LH on glucose variability in a case-crossover study.

The study aim is to assess LH using ultrasound and its impact on glucose variability.

The objectives of the study are:

1. To use ultrasound to characterise (appearance, location, mass, and distribution) LH tissue in participants with T1DM injecting insulin.
2. To develop a standard operating procedure for using US to assess LH.
3. To develop a grading system to evaluate LH using US.
4. To investigate the relationship between the observed LH and glucose variability, glycaemic control, and/or severe hypoglycaemia.
5. To assess quality of life, diabetes distress, and insulin treatment satisfaction after moving to a new injection site and being alerted to the existence of LH.
6. To learn more about how people living with type 1 manage their injection sites.

Study design:

All patients attending the diabetes clinics in Guys and St Thomas' Foundation Trust with type 1 diabetes for more than three years and thought to have LH will be offered the opportunity to participate in the study. Those testing their glucose four or more times a day and with a standard deviation of their mean glucose greater than 4mmols, will be offered to participate in the case-crossover arm of the study; a sub-study, which forms a students doctoral studies.

All participants will be asked to give demographic details and medical history. They will be asked to complete a series of questionnaires about their injection technique, diabetes distress, insulin treatment satisfaction and quality of life. All participants will have a baseline glycated haemoglobin taken, and for those in the case-crossover study an additional 1,5-anhydroglucitol and insulin antibody tests done. The case-crossover study with then be fitted with a continuous glucose monitoring (CGM) device to record their glucose variability for the following six days. They will then return for the US assessment of their injection sites and digital palpation; while all other participants in the characterisation study only, will have had this done at the first visit. All participants will be advised as to where they have LH and where they can inject to avoid LH and after five weeks in the case of the case-crossover study return for a second CGM of six days, and then all participant return after six weeks for the final visit.

At this visit they will complete the questionnaires for a second time and a short exit interview will be conduct to gather information on their experience of injecting into a LH free site and injecting insulin. The glycated haemoglobin will be repeated and for the case-crossover study another 1,5-anhydroglucitol will be taken. Finally, the participants will have a session with a diabetes specialist nurse, who will advise them on maintaining a stable glucose level and refer on as appropriate to their diabetes team.

Eligibility criteria: Inclusion Criteria:

* Adult patients with Type 1 Diabetes Mellitus (T1DM)
* Age\> 20 years
* Taking multiple daily injections ≥4 per/day
* Diagnosed T1DM and using insulin for \>3 years
* Using the same insulin type and delivery method for past 6 months
* Ability to speak and read English

Case-crossover study:

* Glucose variability with a Standard deviation ≥4mmol/l of mean glucose in the previous four weeks
* ≥4 blood glucose tests per/day

Exclusion Criteria:

* Age \<20 years
* Type 2 diabetes or Gestational diabetes mellitus (GDM)
* Have a condition or receiving therapies, other than insulin, associated with lipodystrophies
* Have another medical condition or take medicines that may influence blood glucose control (including: currently active cancer; uncontrolled endocrine disorder; eating disorders; celiac disease; and cystic fibrosis)
* Have a serious medical or mental health condition that impairs full engagement in the research
* Using other injectable treatments in diabetes such as growth hormone or glucagon like peptide-1.
* Using Continuous Subcutaneous Insulin Infusion (CSII)
* Not undertaking blood glucose tests ≥4 tests per day
* Unable to speak English or unable to give consent

Primary outcomes:
measure: Changes in Glucose variability between baseline and follow-up
timeFrame: 6 weeks
measure: Changes in Glycaemic control between baseline and follow-up
timeFrame: 6 Weeks
Secondary outcomes:
Other outcomes:
measure: Time patient spends in the hypoglycaemic/ hyperglycaemic state
timeFrame: 6 weeks
measure: Various glucose variability measures
timeFrame: 6 Weeks
measure: Changes of the Insulin dosage requirements
timeFrame: 6 Weeks
measure: Diabetes Distress
timeFrame: 6 Weeks
measure: Insulin Treatment Satisfaction
timeFrame: 6 Weeks
measure: Health-related quality of life
timeFrame: 6 Weeks
Locations:
city: London
country: United Kingdom
facility: Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care
Study officials:
affiliation: King's College London
name: Angus Forbes, Professor
role: STUDY_DIRECTOR
References: