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.

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).

Trial registration: ClinicalTrials.gov NCT00747409.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diastole
  • Drug Administration Schedule
  • Echocardiography, Doppler, Pulsed
  • Female
  • Germany
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Injections
  • Insulin Aspart / administration & dosage*
  • Insulin Aspart / adverse effects
  • Insulin Detemir / administration & dosage*
  • Insulin Detemir / adverse effects
  • Male
  • Middle Aged
  • Postprandial Period*
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Insulin Detemir
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT00747409