Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Abstract

BackgroundSubclinical myocardial injury, as measured by high‐sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus.Methods and ResultsWe randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT‐proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1–Q3) plasma concentration was 35.4 (15.7–86.3) ng/L for NT‐proBNP and 6.7 (4.6–10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT‐proBNP concentration was 20.7% (7.9–35.0) in the insulin arm compared with 0.13% (−10.8 to 12.5) in the no‐insulin arm (P=0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT‐proBNP was 7.8% (−3.7 to 20.7) compared with 13.0% (0.72–26.8) in the no‐metformin arm (P=0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms.ConclusionsInsulin glargine was associated with a significant 20.7% increase in NT‐proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.

Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial

“…Thorough statistical analysis of hs-cTnI and hs-cTnT levels in the HOME cohort, which previously reported reduced macrovascular disease risk as a result of metformin treatment, did not reveal evidence of a clinically relevant effect of metformin treatment on these cardiac biomarkers, when compared with placebo. Our results corroborate and extend previously published work by Srivastava et al which investigated short-term effects of metformin on circulation concentrations of cardiac troponin T, reporting no significant effect in a population of relatively recent-onset diabetes [ 19 ]. The authors hypothesized that long-term glucose control might lead to reduction in troponin T that was not observed within their 12 week setting.…”

Lactobacillus paracasei JY062 Alleviates Glucolipid Metabolism Disorders via the Adipoinsular Axis and Gut Microbiota

“…In recent years, disorders of glucose and lipid metabolism have gradually become global epidemic diseases, mainly including hyperlipidemia, diabetes, and other diseases, and seriously threatening human health [ 1 ]. Some researchers have found that disorders of glucose and lipid metabolism are caused by a variety of factors, such as the abnormal metabolic processes of glucose and lipid synthesis and decomposition and absorption in the body, which lead to excess lipids, insulin resistance, and liver damage [ 2 ].…”