Effect of Food Composition on Postprandial Insulin Secretion in Neonatal Diabetes

NCT02921906 | Completed

• 1 other identifier: R&D no 1701366
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Neonatal diabetes is diagnosed before 6 months of age and causes high blood glucose levels due to the pancreas not secreting insulin. Neonatal diabetes can be caused by a change in a DNA region called the KCNJ11 gene. KCNJ11 encodes a channel in the pancreas that acts as a switch to turn 'on' and 'off' insulin secretion. A change in KCNJ11 results in a faulty channel, which keeps insulin secretion 'switched off'. The diabetes can be treated with tablets called sulphonylureas that switch the pancreatic channel 'on', allowing it to secrete insulin in response to gut hormones called incretins. Previous research has shown that patients who switch from insulin to sulphonylureas have better blood glucose control, including fewer episodes of hypoglycaemia (glucose dropping too low), and also avoid the need for injections. It is thought that serious side effects from sulphonylureas are uncommon in KCNJ11 neonatal diabetes. Some patients report low glucose after meals and we think this may be because they make too much insulin if they eat a meal with protein but low amounts of carbohydrate. The investigators will test this by giving study participants different meals and measuring the amount of insulin, glucose and incretin hormone in the blood afterwards.

Conditions

Neonatal Diabetes

Keywords

Insulin; Glucose; Incretin; GLP-1; Food

Outcome Measures

Primary Outcomes (2)

• Glucose levels

  Glucose AUC after each meal.

  240 minutes

• Insulin levels

  Insulin AUC after each meal.

  240 minutes

Secondary Outcomes (4)

• GLP-1 levels

  240 minutes

• GIP levels

  240 minutes

• Glucagon levels

  240 minutes

• Paracetamol levels

  240 minutes

Study Arms (3)

Neonatal diabetes

EXPERIMENTAL

People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.

Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol; Other: Fasting state - sulphonylurea only

Non-diabetic controls

ACTIVE COMPARATOR

People without diabetes.

Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol

Controls with Type 2 Diabetes

ACTIVE COMPARATOR

People with Type 2 diabetes who are treated with sulphonylurea medication.

Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol

Interventions

High protein meal OTHER

Breakfast with high protein / low carbohydrate content

Controls with Type 2 Diabetes; Neonatal diabetes; Non-diabetic controls

High carbohydrate meal OTHER

Breakfast with high carbohydrate / low protein content

Controls with Type 2 Diabetes; Neonatal diabetes; Non-diabetic controls

Paracetamol DRUG

Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying.

Also known as: Acetaminophen

Controls with Type 2 Diabetes; Neonatal diabetes; Non-diabetic controls

Fasting state - sulphonylurea only OTHER

People with diabetes take sulphonylurea medication in the absence of any food stimulus

Neonatal diabetes

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥8yrs.
• Willing and able to provide informed consent (adults i.e. participants aged \>16 years).
• Willing and able to provide assent and parents willing to provide informed consent (children and young people \<16 years).

You may not qualify if:

• Age \<8yrs.
• Unable/unwilling to provide informed consent (adults).
• Unable/unwilling to provide assent (children) or parents unwilling to provide informed consent.
• Known liver disease or chronic renal impairment (EGFR \<60ml/min).

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust: lead

Study Sites (1)

Exeter Clinical Research Facility

Exeter, Devon, EX25DW, United Kingdom

Location

Related Publications (1)

• Bowman P, McDonald TJ, Knight BA, Flanagan SE, Leveridge M, Spaull SR, Shields BM, Hammersley S, Shepherd MH, Andrews RC, Patel KA, Hattersley AT. Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways. BMJ Open Diabetes Res Care. 2019 Dec 18;7(1):e000721. doi: 10.1136/bmjdrc-2019-000721. eCollection 2019.

  PMID: 31908791 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Andrew T Hattersley, BMBCh DM FRS

  University of Exeter

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: October 3, 2016
• Study Start: June 1, 2016
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)