Insulin Dose and Cardiovascular Mortality in the ACCORD Trial

Siraj, Elias S.; Rubin, Daniel J.; Riddle, Matthew C.; Miller, Michael E.; Hsu, Fang Chi; Ismail‐Beigi, Faramarz; Chen, Shyh Huei; Ambrosius, Walter T.; Thomas, Abraham; Bestermann, William H.; Buse, John B.; Genuth, Saul; Joyce, Carol; Kovacs, Christopher S.; O’Connor, Patrick J.; Sigal, Ronald J.; Solomon, Sidney

doi:10.2337/dc15-0598

Cited by 36 publications

(31 citation statements)

References 27 publications

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“…Possible explanations that have not been supported include severe hypoglycemia (15); weight gain (R.P. Byington, unpublished analysis); the specific therapies used to lower glucose, including insulin (16) or other glucose-lowering drugs (unpublished analysis); or the differential effects of intensive control in people with underlying cardiac autonomic neuropathy (17). The degree of glucose lowering that was achieved in the intensive group was also not responsible for the mortality signal (18).…”

Section: Discussionmentioning

confidence: 99%

Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes

et al. 2016

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OBJECTIVEIn the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, ∼4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed.RESEARCH DESIGN AND METHODSAll surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider’s judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated.RESULTSA total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02).CONCLUSIONSIn high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.

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Section: Discussionmentioning

confidence: 99%

Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes

et al. 2016

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“…Exposure to injected insulin was hypothesized to increase CV mortality. However, after adjustment for baseline covariates, no significant association of insulin dose with CV death remained (40). Older patients with cognitive dysfunction may not benefit from intensive therapy.…”

Section: Clinical Management Of Type 2 Diabetesmentioning

confidence: 99%

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

Chaudhury¹,

et al. 2017

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Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.

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“…These findings imply that insulin resistance and hyperglycaemia, rather than the use of exogenous insulin is associated with inflammatory activation. In support, a recent analysis in the randomized, placebo-controlled ACCORD trial also could not substantiate the link between insulin dose used and CV events, after adjustment for baseline covariates [26]. …”

Section: Discussionmentioning

confidence: 99%

Carotid arterial wall inflammation in peripheral artery disease is augmented by type 2 diabetes: a cross-sectional study

Moens

Stoekenbroek

Valk

et al. 2016

BMC Cardiovasc Disord

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BackgroundPatients with peripheral artery disease (PAD) are at increased risk of secondary events, which is exaggerated in the presence of type 2 diabetes mellitus. Diabetes is associated with a systemic pro-inflammatory state. We therefore investigated the cumulative impact of PAD and type 2 diabetes on carotid arterial wall inflammation. As recent data suggest a detrimental role of exogenous insulin on cardiovascular disease, we also included a group of insulin users.Results 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) imaging showed increased carotid arterial wall inflammation, assessed as target-to-background ratio (TBR), in PAD patients without diabetes (PAD-only: n = 11, 1.97 ± 0.57) compared with matched controls (n = 12, 1.49 ± 0.57; p = 0.009), with a significant further TBR increase in PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 ± 1, p = 0.033 vs PAD-only). TBR of insulin users (n = 12, 3.31 ± 1.14) was higher compared with patients on oral medication only (n = 11, 2.44 ± 0.76, p = 0.035), despite comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous insulin, correlated with TBR.ConclusionsConcurrent diabetes significantly augments carotid arterial wall inflammation in PAD patients. A further increase in those requiring insulin was observed, which was associated with diabetes severity, rather than with the use of exogenous insulin itself.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0397-x) contains supplementary material, which is available to authorized users.

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Insulin Dose and Cardiovascular Mortality in the ACCORD Trial

Cited by 36 publications

References 27 publications

Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes

Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

Carotid arterial wall inflammation in peripheral artery disease is augmented by type 2 diabetes: a cross-sectional study

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