Ultrasound Classification and Grading of Lipohypertrophy and Its Impact on Glucose Variability in Type 1 Diabetes (TITANIC)

Ultrasound Classification and Grading of Lipohypertrophy and Its Impact on Glucose Variability in Type 1 Diabetes: The TITANIC Studies.

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus; Lipohypertrophy

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.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 8WA
    • Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Glucose variability between baseline and follow-up	Glucose variability will be measured using the standard deviation of the mean glucose measured at visit 1 and the last visit. For the case-crossover study the data will be taken from the CGM recording and the other participants with their own self-monitoring of glucose measurements.	6 weeks
Changes in Glycaemic control between baseline and follow-up	Glycaemic control will be assessed in all participants using glycated haemoglobin at first clinical outpatient appointment and at six weeks. In addition, participants at the case-crossover study will have a 1, 5 anhydroglucitol taken at study visit 1 and at six weeks.	6 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time patient spends in the hypoglycaemic/ hyperglycaemic state	Time spend in the hypoglycaemic (Low blood glucose) and hyperglycaemic (High blood glucose) range as indicated by Continuous Glucose Monitoring data.	6 weeks
Various glucose variability measures	standard deviation(SD) of mean glucose; coefficient of variation (CV); mean amplitude of glycaemic excursion(MAGE); continuous overall net glycaemic action(CONGA-n); and mean of daily differences(MODD). These will be identified from the Continuous Glucose Monitoring data.	6 Weeks
Changes of the Insulin dosage requirements	Total daily dose (proportion of basal and bolus insulin) at baseline and follow-up	6 Weeks
Diabetes Distress	Diabetes distress will be measured using the 17-item diabetes distress scale at baseline and follow-up (Polonsky et al. 2005, Fisher et al. 2008).	6 Weeks
Insulin Treatment Satisfaction	Insulin Treatment Satisfaction Questionnaire (ITSQ) at baseline and follow-up (Anderson et al. 2004)	6 Weeks
Health-related quality of life	Health related quality of life be assessed with the EuroQol EQ-5D-5L questionnaire at baseline and follow-up (Herdman et al. 2011).	6 Weeks

Collaborators and Investigators

• Sponsor: King's College London
• Investigators: Study Director: Angus Forbes, Professor, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Actual): April 25, 2018
• Study Completion (Actual): April 25, 2018

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Ultrasound; Type 1 Diabetes Mellitus; Glycaemic control; Lipohypertrophy; Glucose variability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 217187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No