Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis
Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis
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.
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.
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.