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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neonatal diabetes | Experimental | People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin. |
|
| Non-diabetic controls | Active Comparator | People without diabetes. |
|
| Controls with Type 2 Diabetes | Active Comparator | People with Type 2 diabetes who are treated with sulphonylurea medication. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High protein meal | Other | Breakfast with high protein / low carbohydrate content |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glucose levels | Glucose AUC after each meal. | 240 minutes |
| Insulin levels | Insulin AUC after each meal. | 240 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| GLP-1 levels | GLP-1 AUC after each meal. | 240 minutes |
| GIP levels | GIP AUC after each meal. | 240 minutes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew T Hattersley, BMBCh DM FRS | University of Exeter | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Exeter Clinical Research Facility | Exeter | Devon | EX25DW | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31908791 | Derived | 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. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 6, 2023 | |
| Reset | Mar 21, 2024 | |
| Release | Apr 9, 2025 | |
| Reset | Apr 28, 2025 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 6, 2023 | Mar 21, 2024 | |||
| Apr 9, 2025 |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000082 | Acetaminophen |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 |
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| High carbohydrate meal | Other | Breakfast with high carbohydrate / low protein content |
|
| Paracetamol | Drug | Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying. |
|
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| Fasting state - sulphonylurea only | Other | People with diabetes take sulphonylurea medication in the absence of any food stimulus |
|
| Glucagon levels | Glucagon AUC after each meal. | 240 minutes |
| Paracetamol levels | Rate of change of paracetamol levels after each meal as marker of gastric emptying. | 240 minutes |
| Apr 28, 2025 |
| Aniline Compounds |
| D000588 | Amines |