Insulin Effects on Metabolism and Cardiovascular Function in Type 2 Diabetes

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.

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: human regular insulin and NPH insulin (Actrapid, Protaphne); Drug: insulin aspart and detemir (NovoRapid, Levemir)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81925
      • Staedt. Klinikum Muenchen Bogenhausen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• type 2 diabetes, insulin therapy

Exclusion Criteria:

• type 1 diabetes, BMI >40, pregnancy,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hum; use of human regular insulin and NPH insulin	Drug: human regular insulin and NPH insulin (Actrapid, Protaphne); basal-bolus therapy with human regular and NPH insulin; Other Names: Insulin Actrapid, Insulin Protaphne
Active Comparator: Ana; use of insulin aspart and insulin detemir	Drug: insulin aspart and detemir (NovoRapid, Levemir); use of basal-bolus therapy with insulin aspart and detemir; Other Names: Insulin NovoRapid, Insulin Levemir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
postprandial blood glucose at the end of the study and its change from baseline.	24-48 months treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
diastolic myocardial function	24-48 months treatment

Collaborators and Investigators

• Sponsor: Munich Municipal Hospital
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Petra-Maria Schumm-Draeger, MD, PHD, Munich Academic Teaching Hospital Bogenhausen; Study Chair: Helene von Bibra, MD, PHD, Munich Academic Teaching Hospital Bogenhausen

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: Diabetologia 1999 Dec;42(12):1444.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Anticipated): March 1, 2009
• Study Completion (Anticipated): June 1, 2009

Study Registration Dates

• First Submitted: September 4, 2008
• First Submitted That Met QC Criteria: September 4, 2008
• First Posted (Estimate): September 5, 2008

Study Record Updates

• Last Update Posted (Estimate): September 5, 2008
• Last Update Submitted That Met QC Criteria: September 4, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: postprandial glucose, diastolic function, analogue insulins
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: AnaHum