Clinical trial NCT00747409: Insulin Effects on Metabolism and Cardiovascular Function in Type 2 Diabetes
Official title: Randomized, Long-Term Study About the Effects of Analogue Versus Human Insulin Based Regimens (Insulin Detemir and Aspart Versus NPH- and Regular Human Insulin) on Metabolic Control and Myocardial Function in People With Type 2 Diabetes.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: postprandial glucose, diastolic function, analogue insulins
Lead sponsor: Munich Municipal Hospital
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2008-09-05
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Compared to human insulins analogue insulins offer the option of optimizing metabolism also in type 2 diabetes. Especially, fast acting insulin analogues lower postprandial glucose levels more effectively than human regular insulin. However, it is not known whether therapy with analogue insulins can also improve the subclinically impaired myocardial function in type 2 diabetes. This prospective, randomized, open long term study compared the effects of a basal-bolus insulin therapy with analogue insulins versus human insulins on metabolic control and systolic and diastolic myocardial function, testing the hypothesis that optimized postprandial glucose control improves cardiac function and cardiovascular risk.

Detailed description: This is a single centre, long term (24-48 months), therapy controlled and randomised study with blinded analysis of the ultrasound data in 120 patients with type 2 diabetes mellitus and with previous insulin therapy. After recruitment and informed consent, patients are randomized to two treatment arms according to a randomisation protocol which takes into account age and absence or presence of cardiovascular events in each patient's history.

In one treatment arm, the intensive insulin therapy is based on human insulin (insulin NPH and regular human insulin) while in the other arm, the intensive insulin therapy is based on analogue insulin (insulin detemir and insulin aspart). Both treatment arms will be titrated to identical glycemic goals (fasting blood glucose \<110 mg/dL and post prandial blood glucose \<150 mg/dL).

All patients will be updated in their skills of self medication by the departmental diabetic teaching programme und will receive life style instructions during each visit. Furthermore, they are encouraged to keep records of any episode of hypoglycemia throughout the study. Outpatient visits for metabolic control are every 3 months and ultrasound and blood tests every 6 months.

Eligibility criteria: Inclusion Criteria:

* type 2 diabetes, insulin therapy

Exclusion Criteria:

* type 1 diabetes, BMI \>40, pregnancy,

Primary outcomes:
measure: postprandial blood glucose at the end of the study and its change from baseline.
timeFrame: 24-48 months treatment period
Secondary outcomes:
measure: diastolic myocardial function
timeFrame: 24-48 months treatment
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Staedt. Klinikum Muenchen Bogenhausen
state: Bavaria
Study officials:
affiliation: Munich Academic Teaching Hospital Bogenhausen
name: Petra-Maria Schumm-Draeger, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Munich Academic Teaching Hospital Bogenhausen
name: Helene von Bibra, MD, PHD
role: STUDY_CHAIR
References:
citation: Bretzel RG, Arnolds S, Medding J, Linn T. A direct efficacy and safety comparison of insulin aspart, human soluble insulin, and human premix insulin (70/30) in patients with type 2 diabetes. Diabetes Care. 2004 May;27(5):1023-7. doi: 10.2337/diacare.27.5.1023.
citation: von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Ryden L. Augmented metabolic control improves myocardial diastolic function and perfusion in patients with non-insulin dependent diabetes. Heart. 2004 Dec;90(12):1483-4. doi: 10.1136/hrt.2003.020842. No abstract available.
citation: Shaw JE, Hodge AM, de Courten M, Chitson P, Zimmet PZ. Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality. Diabetologia. 1999 Sep;42(9):1050-4. doi: 10.1007/s001250051269.
citation: von Bibra H, Siegmund T, Kingreen I, Riemer M, Schuster T, Schumm-Draeger PM. Effects of analogue insulin in multiple daily injection therapy of type 2 diabetes on postprandial glucose control and cardiac function compared to human insulin: a randomized controlled long-term study. Cardiovasc Diabetol. 2016 Jan 16;15:7. doi: 10.1186/s12933-015-0320-2.