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

BackgroundThe 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.MethodsFor 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 [ ].ResultsAt 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.ConclusionsMDI 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)

Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes

“…Thus, a reduction of the postprandial glucose increase by the short-acting IA aspart was shown to be associated with a significant improvement in myocardial perfusion and diastolic heart function. 18,19 The microvascular circulation of the skin showed that the IAs lispro and glulisine also improve the microvascular circulation by reducing the postprandial increase in blood glucose. 20,21 The reduction of the risk of hypoglycemia under the treatment with long-acting IAs compared with human NPH insulin is also a factor in reducing CV risk in insulin-dependent patients.…”

Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment

“…The scope for insulin‐induced glucose variability is particularly great with basal insulin because of its prolonged absorption resulting from high‐dose subcutaneous depots. Although rapid/short‐acting insulin might reduce post‐meal glucose excursions in multiple daily injection, as will be discussed later, long‐acting insulin analogs can more effectively mimic the constitutive secretion of endogenous insulin than NPH, the conventional basal insulin, thereby reducing glycemic variability.…”

Dose modification of antidiabetic agents in patients with type 2 diabetes mellitus and heart failure

“…[ 129 ] Recently, an RCT in patients with T2DM and diastolic dysfunction found that the insulin analogs (insulin detemir, insulin aspart, and NPH-insulin) treatment was associated with improved diastolic cardiac function, compared to human insulin. [ 130 ] An ongoing trial comparing CV safety of insulin Degludec Versus insulin glargine in subjects with Type 2 Diabetes at high risk of cardiovascular Events (DEVOTE) will give further insights on use of insulin analogs in patients who are at high risk of CV events [ Table 11 ]. [ 131 ]…”