Flat and Circadian Insulin Infusion Rates in Continuous Subcutaneous Insulin Infusion

Not Applicable

Completed

Conditions: Type 1 Diabetes

Interventions: Drug: Insulin (flat rate)
Drug: Insulin (circadian)

Registration Number: NCT04267770

Lead Sponsor: Imperial College London

Brief Summary: Randomised controlled trial to contribute to the evidence base for the optimal initial insulin profile for adults with type 1 diabetes commencing insulin pump therapy.

Detailed Description: Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a basal insulin dose, given as once or twice daily long-acting insulin, to a continuous basal infusion regimen. This conversion may be based on basal insulin dose only, or total daily insulin dose, and may result in a flat basal insulin profile or an initial variable basal rate.

Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years. Initial rates were developed from 63 well-controlled people with type 1 diabetes over 14 years of age and have been assessed against a flat basal rate in a small randomised controlled trial with 12 participants. Mean glucose was lower in the circadian basal rate group with particular differences noted in the early morning when glucose rises were more pronounced in the flat basal rate group1.

In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those with lower basal rates at midnight, and in those with higher basal rates in the afternoon, suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years of age basal rate distribution established at commencement of pump therapy did not alter over 6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates showed no difference in HbA1c4.

Following initiation on insulin pump therapy basal rates are personalised to capillary blood and continuous interstitial fluid glucose monitoring.

In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimise healthcare professional input.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Adults ≥18 years of age
Diagnosis of T1DM for > 1 year
On MDI with decision made to commence CSII
Structured education in previous 3 years
HbA1c ≤ 75mmol/mol (9%)
Stimulated c-peptide <200pmol/L
No severe hypoglycaemia (defined as needing 3rd party assistance) in previous year

Exclusion Criteria

Previous CSII
Night or shift worker
Recurrent severe hypoglycaemia
Pregnant or planning pregnancy
Breastfeeding
Enrolled in other clinical trials
Have active malignancy or under investigation for malignancy
Addison's Disease
Gastroparesis
Autonomic neuropathy
Concomitant use of GLP-1 analogues and gliptins
Visual impairment
Reduced manual dexterity

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
flat rates	Insulin (flat rate)	flat basal rate
circadian insulin infusion rates	Insulin (circadian)	Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years.

Primary Outcome Measures

Name	Time	Method
Change in Basal Insulin Rate	over 24 hours after 3 rounds of basal rate testing	Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing (calculated by the sum of absolute changes for each 1 hour block compared with baseline)

Secondary Outcome Measures