Effect of Food Composition on Postprandial Insulin Secretion in Neonatal Diabetes

Not Applicable

Completed

• Conditions: Neonatal Diabetes
• Interventions: Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol; Other: Fasting state - sulphonylurea only

• Registration Number: NCT02921906
• Lead Sponsor: Royal Devon and Exeter NHS Foundation Trust

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.

Detailed Description

Anecdotal evidence from routine clinical care suggests that patients with sulphonylurea-treated KCNJ11 neonatal diabetes, when they eat, may experience mild hypoglycaemia if the food consumed lacks carbohydrate. It has been suggested that this may be due to regulation of insulin secretion via the incretin pathway as opposed to the classical ATP pathway. Therefore the investigators hypothesise that foods with a relatively high protein content compared to those with a relatively high carbohydrate content will result in excessive insulin secretion and relatively lower glucose values in KCNJ11 patients. This would be in contrast to healthy control subjects or subjects with SU-treated T2D where the insulin secretion will be moderated by the ambient glucose via the classical ATP pathway. The investigators will formally study this hypothesis by comparing the insulin, glucose and incretin hormone responses to a high protein meal with a high carbohydrate meal in people with KCNJ11 neonatal diabetes, people without diabetes and people with sulphonylurea-treated Type 2 Diabetes. To assess whether any effect seen is due to direct stimulation of the beta cell by the sulphonylurea itself, people with KCNJ11 neonatal diabetes will also undergo the same tests in the fasting state, having taken the sulphonylurea in the absence of any food.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-06
• Study First Submitted: 2016-09-20
• Study First Submitted QC: 2016-09-29
• Study First Posted: 2016-10-03
• Primary Completion: 2022-06-20
• Study Completion: 2022-06-20
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-27
• Last Update Posted: 2022-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• 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).

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Exclusion Criteria

• 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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Non-diabetic controls	High protein meal	People without diabetes.
Non-diabetic controls	High carbohydrate meal	People without diabetes.
Controls with Type 2 Diabetes	High protein meal	People with Type 2 diabetes who are treated with sulphonylurea medication.
Neonatal diabetes	Fasting state - sulphonylurea only	People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.
Neonatal diabetes	High protein meal	People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.
Controls with Type 2 Diabetes	High carbohydrate meal	People with Type 2 diabetes who are treated with sulphonylurea medication.
Neonatal diabetes	High carbohydrate meal	People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.
Neonatal diabetes	Paracetamol	People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.
Non-diabetic controls	Paracetamol	People without diabetes.
Controls with Type 2 Diabetes	Paracetamol	People with Type 2 diabetes who are treated with sulphonylurea medication.

Primary Outcome Measures

Name	Time	Method
Insulin levels	240 minutes	Insulin AUC after each meal.
Glucose levels	240 minutes	Glucose AUC after each meal.

Secondary Outcome Measures

Name	Time	Method
GLP-1 levels	240 minutes	GLP-1 AUC after each meal.
Glucagon levels	240 minutes	Glucagon AUC after each meal.
GIP levels	240 minutes	GIP AUC after each meal.
Paracetamol levels	240 minutes	Rate of change of paracetamol levels after each meal as marker of gastric emptying.

Trial Locations

Locations (1)

Exeter Clinical Research Facility; 🇬🇧 Exeter, Devon, United Kingdom