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临床试验/NCT02921906
NCT02921906已完成不适用

Assessing the Effect of Food Composition on Postprandial Insulin Secretion in KCNJ11 Neonatal Diabetes (FoND Study)

Royal Devon and Exeter NHS Foundation Trust1 个研究点 分布在 1 个国家目标入组 16 人开始时间: 2016年6月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
16
试验地点
1
主要终点
Insulin levels

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Crossover
主要目的
Basic Science
盲法
None

入排标准

年龄范围
8 Years 至 —(Child, Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 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).

排除标准

  • 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).

研究组 & 干预措施

Neonatal diabetes

Experimental

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

干预措施: Paracetamol (Drug)

Neonatal diabetes

Experimental

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

干预措施: High protein meal (Other)

Neonatal diabetes

Experimental

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

干预措施: High carbohydrate meal (Other)

Neonatal diabetes

Experimental

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

干预措施: Fasting state - sulphonylurea only (Other)

Non-diabetic controls

Active Comparator

People without diabetes.

干预措施: High protein meal (Other)

Non-diabetic controls

Active Comparator

People without diabetes.

干预措施: High carbohydrate meal (Other)

Non-diabetic controls

Active Comparator

People without diabetes.

干预措施: Paracetamol (Drug)

Controls with Type 2 Diabetes

Active Comparator

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

干预措施: High protein meal (Other)

Controls with Type 2 Diabetes

Active Comparator

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

干预措施: High carbohydrate meal (Other)

Controls with Type 2 Diabetes

Active Comparator

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

干预措施: Paracetamol (Drug)

结局指标

主要结局

Insulin levels

时间窗: 240 minutes

Insulin AUC after each meal.

Glucose levels

时间窗: 240 minutes

Glucose AUC after each meal.

次要结局

  • GLP-1 levels(240 minutes)
  • Glucagon levels(240 minutes)
  • GIP levels(240 minutes)
  • Paracetamol levels(240 minutes)

研究者

发起方
Royal Devon and Exeter NHS Foundation Trust
申办方类型
Other
责任方
Sponsor

研究点 (1)

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