Diabetes prevention and cardiovascular complications
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LETTER
Diabetes prevention and cardiovascular complications Silvio E. Inzucchi 1 & Catherine M. Viscoli 2 & Lawrence H. Young 3 & Walter N. Kernan 2 Received: 28 July 2019 / Accepted: 31 July 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019
Keywords Cardiovascular disease . Complications . Diabetes prevention . Impaired fasting glucose . Impaired glucose tolerance . Pioglitazone . Thiazolidinediones
Abbreviations ACT NOW Actos Now for Prevention of Diabetes ASCVD Atherosclerotic cardiovascular disease CV Cardiovascular IFG Impaired fasting glucose IGT Impaired glucose tolerance IRIS Insulin Resistance Intervention after Stroke MI Myocardial infarction RRR Relative risk reduction
To the Editor: The review by Nathan et al recently published in Diabetologia provides an excellent discussion of the relationship between diabetes prevention and microvascular and cardiovascular (CV) complications [1]. We agree that the existing data are quite limited, although somewhat more robust for microvascular disease. This is not unexpected, given that hyperglycaemia is more closely aligned with retinopathy and nephropathy than with atherosclerotic CV disease (ASCVD). We noted one important omission, however, from this otherwise complete review. Insulin Resistance Intervention after Stroke (IRIS) was a large, multi-national clinical trial, funded by the US National Institutes of Health, that randomised insulin-resistant (but non-diabetic) individuals with recent stroke or transient ischaemic attack to receive the thiazolidinedione pioglitazone or placebo and assessed the * Silvio E. Inzucchi [email protected] 1
Section of Endocrinology/Fitkin 106, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520–8020, USA
2
Section of General Medicine, Yale School of Medicine, New Haven, CT, USA
3
Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, USA
impact on future CVevents as well as the diagnosis of diabetes [2]. Pioglitazone is a potent insulin-sensitising drug and, as Nathan et al point out, it prevented diabetes in individuals with impaired glucose tolerance (IGT) in the Actos Now for Prevention of Diabetes (ACT NOW) trial [3]. That study, which predominately involved patients without known ASCVD, also demonstrated a simultaneous benefit of pioglitazone on the progression of early carotid atherosclerosis, but was too small (N=602) and brief (2.4 years) to adequately assess clinical CV events. In contrast, IRIS, which included 3876 patients with known cerebrovascular disease and a median follow-up of 4.8 years, demonstrated a 24% relative risk reduction (RRR) in the primary outcome of fatal/non-fatal stroke or myocardial infarction (MI) (p=0.007) with pioglitazone vs placebo (Fig. 1) [2]. Subsequently, using updated outcome definitions, we also reported statistically significant RRRs with pioglitazone for stroke alone (25%), exclusively driven by ischaemic stroke (28%) [4], as well as for acute coronary syndrome (29%), predominately driven by a large effect on type 1 MI (
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