The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of Glucose-dependent Insulinotropic Polypeptide (GIP) in Patients With Type 2 Diabetes is Not Caused by Rapid Tachyphylaxis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 主要终点
- Insulin secretory response after GIP bolus or infusion.
研究概览
简要总结
In patients with type 2 diabetes, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has lost its insulinotropic activity, but more so after continuous versus bolus administration. The design was a two-way crossover design comparing repeated bolus injection and continuous infusion of GIP under hyperglycaemic clamp conditions. Patients were age- gender- and weight-matched with type 2 diabetes, first degree relatives of such patients, and healthy subjects. Investigators performed a:
- Oral glucose challenge;
- hyperglycemic clamp (8.5 mmol/l) with two repeated GIP bolus administrations (50 pmol/kg body weight at 30 and 120 min); and
- hyperglycemic clamp with continuous administration of GIP (2 pmol.kg-1.min-1 from 30-180 min).
To answer the question, whether rapid tachyphylaxis occurs with regard to the insulinotropic action of GIP, investigators studied type 2-diabetic patients, their first-degree relatives, and healthy controls under hyperglycaemic clamp conditions with two GIP bolus injections 90 min apart, and compared this to a continued intravenous infusion of GIP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Exclusion of pregnancy
- •Exclusion of impaired glucose tolerance or type 2 diabetes in metabolical healthy subjects
- •current diagnosis of type 2 diabetes according to the guidelines of the German Diabetes Association (DDG) ( Kerner et al . 2001) in subjects of diabetes group
- •fasting glucose ≤ 150 mg/dl
- •Body-mass-index ≥ 20 kg/m²
- •Written consent
排除标准
- •Type 1 diabetes
- •Impaired glucose tolerance or Type 2 diabetes in metabolical healthy subjects
- •Ketone bodies urine diagnostics at least ++
- •Fasting blood glucose > 150 mg/dl
- •Body-mass-index < 20 kg/m²
- •No written consent
- •Pregnancy or unsafe contraception in women before menopause
- •Active malignancy
- •Angina as current, unsolved clinical problem
- •Inadequately treated or untreated arterial hypertension ( > 160 mmHg systolic and / or > 95 mmHg diastolic )
- •Infection / fever > 37.5 ° C
- •Treatment with glucocorticoids
- •Insulin therapy within the last three months
- •Anemia with a hemoglobin level < 12 g/dl
- •Liver function limitations
- •Renal impairment ( serum creatinine > 1.5 mg/dl )
- •Alcohol or drug abuse
- •Participation in clinical trials in the last 3 months
- •Inability or unwillingness to comply with the requirements of the Protocol
- •Known hypersensitivity to GIP
研究组 & 干预措施
Oral glucose tolerance test
An oral glucose challenge (75 g)
干预措施: Oral glucose tolerance test (OGTT) (Procedure)
GIP Bolus
Hyperglycemic clamp (capillary venous glucose concentration ~ 8.5 mmol/l) with two repeated intravenous bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp
干预措施: GIP Bolus (Drug)
GIP Bolus
Hyperglycemic clamp (capillary venous glucose concentration ~ 8.5 mmol/l) with two repeated intravenous bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp
干预措施: hyperglycemic clamp (Procedure)
GIP Infusion
Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min
干预措施: GIP Clamp (Drug)
GIP Infusion
Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min
干预措施: hyperglycemic clamp (Procedure)
结局指标
主要结局
Insulin secretory response after GIP bolus or infusion.
时间窗: 210 minutes
次要结局
未报告次要终点
研究者
Michael A. Nauck
Prof. Dr. med. Michael A. Nauck
Diabeteszentrum Bad Lauterberg im Harz