Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial

Abstract

Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODS -Patients (type 2 diabetes, aged 30 -75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose Ͻ7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose Ͻ6.7 mmol/l).RESULTS -A total of 1,115 patients were randomly assigned (PRANDIAL n ϭ 557; BASAL n ϭ 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n ϭ 174, 31.2%) and BASAL (n ϭ 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8 -1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 Ϯ 0.1 vs. 7.8 Ϯ 0.1%; P ϭ 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P Ͻ 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P Ͻ 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P Ͻ 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P ϭ 0.233) versus the PRANDIAL group.CONCLUSIONS -Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD – Summary

“…91 Although postprandial hyperglycaemia is associated with an increased incidence of CVD events, it is controversial as to whether addressing this is of benefit for CVD outcomes. [92][93][94][95] More stringent targets (e.g. HbA 1c 6.0-6.5% (42-48 mmol/mol]) might be considered in selected patients with short disease duration, long life expectancy, and no significant CVD, if achieved without hypoglycaemia or other adverse effects.…”

“…The study was stopped after an average follow-up of 963 days, due to lack of efficacy. 94 Recommendations for the management of patients with stable and unstable coronary artery disease and diabetes. Some registry studies suggest there is a J-or U-shaped relationship between PG and prognosis, 220,222,223 with the implication that both hypoglycaemia and hyperglycaemia are unfavourable.…”

Effect of Short-term Polyphenol Treatment on Endothelial Dysfunction and Thromboxane A₂ Levels in Streptozotocin-Induced Diabetic Mice

“…4) Hyperglycemia itself is likely to increase the risk via a number of mechanisms that may encompass a combination of acute and chronic inflammation. An inflammation-centered model suggests that this risk may be driven by increased endothelial dysfunction.…”

“…An inflammation-centered model suggests that this risk may be driven by increased endothelial dysfunction. 5) Endothelial dysfunction is a major event in the pathogenetic cascade leading to cardiovascular events, 4) and therapies aiming at preserving the endothelium are needed for the effective prevention of cardiovascular disease. The endothelium plays a central role in physiological maintenance of the vascular function by regulating vascular tone, leukocyte adhesion, and platelet activation, as a result of the release of vasoactive substances such as nitric oxide (NO), prostacyclin, and thromboxane A 2 (TXA 2 ).…”

A prospective, randomized, multicenter trial comparing the efficacy and safety of the concurrent use of long-acting insulin with mitiglinide or voglibose in patients with type 2 diabetes

“…The clinical trial was carried out at 9 clinical trial centers from February 2008 to June 2009. Patients were divided into groups and received either insulin glargine plus 10 mg of mitiglinide three times daily or insulin glargine plus 0.2 mg of voglibfor cardiovascular disease and that lowered PPG levels are associated with a reduced risk of atherosclerosis and cardiovascular events [6][7][8]. Thus, many clinicians consider several therapeutic strategies for reducing PPG excursions.…”