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

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

• Informed consent obtained before any trial-related activities.
• Diagnosis of diabetes mellitus according to WHO criteria; history and clinical course consistent with type 1 diabetes mellitus.
• Diagnosed with diabetes for more than 6 years and using continuous subcutaneous insulin infusion (CSII) at least 6 months at time of inclusion.
• Total daily insulin dose between 0.4 and 1.4 units/kg (both values included)
• HbA1c between 6% and 9% (both values included).
• Age ≥ 18 years.
• BMI between 18.5 and 28 kg /m2 (including both values).

Exclusion criteria

• Known or suspected allergy to trial product(s) or related products.
• Recurrent major hypoglycaemic episodes.
• Heart: Unstable Angina Pectoris, AMI < 12 months or heart insufficiency classified according to NYHA III-IV
• Blood Pressure: Severe uncontrolled hypertension with BP > 180/110 mmHg, sitting
• Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase > 2 x upper reference limit of the local laboratory.
• Kidneys: Impaired renal function corresponding to serum-creatinin > 150 μmol/l according to the local laboratory.
• Any disease judged by the investigator to affect the trial.
• 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.