Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1
Brief summary
The objective is to describe the interaction of equal doses of NPH insulin (Neutral Protamine Hagedorn), insulin Detemir and insulin glargine on IGFBP-1 (Insulin-like Growth Factor Binding Protein-1) production as well as immunoreactive and bioactive IGF-I (Insulin-like Growth Factor-I) after once-daily injection on three separate visits in type 1 diabetic subjects.
Detailed description
Because of the importance of receptors activation and potential effects on the IGF system, a head-to-head comparison of the eventual differential impact of intermediate-acting human insulin (NPH), insulin detemir and insulin glargine on the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis is relevant to be conducted for the safety assurance of insulin analogues. Therefore, this study aims to investigate whether the serum insulin profile obtained by once-daily injection of long-acting insulin analog, insulin detemir or insulin glargine, has a different impact on IGFBPs production and IGF-I concentrations (total IGF-I) bioactivity and tissue-availability as compared to that seen during treatment with intermediate-acting human insulin, NPH insulin.
Interventions
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent obtained before any trial-related activities. 2. Diagnosis of diabetes mellitus according to WHO criteria; history and clinical course consistent with type 1 diabetes mellitus. 3. Diagnosed with diabetes for more than 6 years and using continuous subcutaneous insulin infusion (CSII) at least 6 months at time of inclusion. 4. Total daily insulin dose between 0.4 and 1.4 units/kg (both values included) 5. HbA1c between 6% and 9% (both values included). 6. Age ≥ 18 years. 7. BMI between 18.5 and 28 kg /m2 (including both values).
Exclusion criteria
1. Known or suspected allergy to trial product(s) or related products. 2. Recurrent major hypoglycaemic episodes. 3. Heart: Unstable Angina Pectoris, AMI \< 12 months or heart insufficiency classified according to NYHA III-IV 4. Blood Pressure: Severe uncontrolled hypertension with BP \> 180/110 mmHg, sitting 5. Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase \> 2 x upper reference limit of the local laboratory. 6. Kidneys: Impaired renal function corresponding to serum-creatinin \> 150 μmol/l according to the local laboratory. 7. Any disease judged by the investigator to affect the trial. 8. Pregnancy, breast-feeding or the intention of becoming pregnant or fertile women not using adequate contraceptive measures - adequate contraceptive method is sterilisation, hysterectomy or current use of contraceptive pills or intra uterine device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IGFBP-1(ng/ml) | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
| IGFBP-3(ng/ml) | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
| Growth Hormone(ng/ml) | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
| IGF-I(ng/ml) | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
| IGFBP-2(ng/ml) | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| insulin concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
| plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine | 16 hours (from 18:00 to 10:00 next day) | Hourly samples will be taken from 18:00 to 10:00 next day. |
Countries
Denmark
Outcome results
None listed