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

University of Aarhus19 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 1

Interventions

NPHDRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

DetemirDRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

GlargineDRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, Denmark