title: 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.
abstract: BACKGROUND
  The prevention of cardiovascular disease, including diastolic cardiac dysfunction with its high prevalence and ominous prognosis, is a therapeutic challenge for patients with type 2 diabetes. Both short and long-acting insulin analogues (AI) have been shown to reduce glucose variability and provide potential benefit for cardiovascular disease although the effects on cardiac function have not yet been evaluated. This long-term, prospective, randomized controlled trial in patients with type 2 diabetes (T2D) tested the hypothesis that a multiple daily injection regimen (MDI) with AI improves postmeal glucose excursions in comparison to human insulin (HI) and that the effects of AI improve diastolic cardiac function.
  
  
  METHODS
  For 36 months, MDI treatment in 109 T2D patients was adapted every 3 months (targets: fasting glucose ≤ 110 mg/dl, postmeal glucose ≤ 150 mg/dl) in both groups: AI (insulin detemir and insulin aspart, n = 61) and HI (NPH-insulin and regular HI, n = 48). Diastolic cardiac function (myocardial velocity E' using tissue Doppler imaging and the mitral inflow ratio E/A) and vascular function were assessed before and 2 h after a standardized breakfast (48 g carbohydrates). At baseline, both groups were comparable with regards to demographic, cardiac and metabolic data. Analysis of data included traditional statistics as well as the use of a multiple imputation technique shown in brackets [ ].
  
  
  RESULTS
  At 36 months, the primary endpoint, postmeal glucose, decreased by 20 ± 62 mg/dl, p = 0.038 [p = 0.021] with AI and increased insignificantly with HI (inter-group p = 0.032 [p = 0.047]) to postmeal glucose levels of 161 ± 39 with AI vs. 195 ± 54 mg/dl with HI (inter-group p = 0.002 [p = 0.010]) whereas the levels of fasting glucose and HbA1c were comparable. With AI, postmeal E' improved by 0.6 ± 1.4 cm/s, p = 0.009 [p = 0.002] and fasting E' by 0.4 ± 1.4 cm/s, p = 0.069 [p = 0.013], however, E' remained unchanged with HI. These changes were consistent with those of the traditional parameter E/A.
  
  
  CONCLUSIONS
  MDI with AI results in better postmeal glucose control compared to HI. The treatment with AI is associated with improved diastolic cardiac function. ClinicalTrials.gov (NTC00747409).
authors.affiliation: Clinic for Endocrinology, Diabetes and Vascular Medicine, Klinikum Bogenhausen, Städt. Klinikum München GmbH, Munich, Germany. vonbibra@gmx.de.
authors.forename: Helene
authors.initials: H
authors.lastname: von Bibra
authors.affiliation: Clinic for Endocrinology, Diabetes and Vascular Medicine, Klinikum Bogenhausen, Städt. Klinikum München GmbH, Munich, Germany. thorsten_siegmund@gmx.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Siegmund
authors.affiliation: Clinic for Endocrinology, Diabetes and Vascular Medicine, Klinikum Bogenhausen, Städt. Klinikum München GmbH, Munich, Germany. iris.kingreen@gmail.com.
authors.forename: Iris
authors.initials: I
authors.lastname: Kingreen
authors.affiliation: Clinic for Endocrinology, Diabetes and Vascular Medicine, Klinikum Bogenhausen, Städt. Klinikum München GmbH, Munich, Germany. dr.riemer-praxis@web.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Riemer
authors.affiliation: Institute for Statistics and Epidemiology in Medicine of the Technische Universität, Munich, Germany. tibor.schuster@gmail.com.
authors.forename: Tibor
authors.initials: T
authors.lastname: Schuster
authors.affiliation: Clinic for Endocrinology, Diabetes and Vascular Medicine, Klinikum Bogenhausen, Städt. Klinikum München GmbH, Munich, Germany. petra-maria.schumm-draeger@klinikum-muenchen.de.
authors.forename: Petra-Maria
authors.initials: PM
authors.lastname: Schumm-Draeger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003971:Diastole; D004334:Drug Administration Schedule; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D005858:Germany; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007267:Injections; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000009:adverse effects; D000069057:Insulin Detemir / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D000069057:Insulin Detemir; C517652:hemoglobin A1c protein, human