Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes: A meta-analysis

Zhang, Chunyu; Sun, Aijun; Zhang, Shuning; Wu, Chunlei; Fu, Mingqiang; Xia, Guang; Wang, Keqiang; Zou, Yunzeng; Ge, Junbo

doi:10.3109/07853891003796752

Cited by 31 publications

(23 citation statements)

References 32 publications

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“…Although this result is seemingly contradicted by the UKPDS (3), where beneficial effects of intensive glycemic control emerged only after relatively lengthy follow-up of 10-20 years, at the end of the original UKPDS (20), intensive glycemic control showed a borderline preventive effect on MI. In addition, meta-analyses of randomized trials of intensive glycemic control have shown a preventive effect on MI after ;5 years of follow-up (21,22). The present results, in combination with previous findings, indicate that glycemic control is important to the prevention of MI and, more importantly, perhaps within a shorter time perspective than 10-20 years.…”

Section: Discussionsupporting

confidence: 76%

Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes

et al. 2015

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OBJECTIVEThis study evaluated the risk of myocardial infarction (MI) by impaired glycemic control in a contemporary large cohort of patients with type 2 diabetes followed from diagnosis. RESEARCH DESIGN AND METHODSPatients with type 2 diabetes diagnosed between 1995 and 2011 were retrieved from the Clinical Practice Research Datalink in the U.K., and followed from diagnosis until event of MI or end of study in 2013. Two subcohorts were defined: an early cohort with those diagnosed from 1997 to 2004 and a recent cohort with those diagnosed from 2004 to 2011. Association between each of three HbA 1c metrics and MI was estimated using adjusted proportional hazards models. RESULTSIn the overall cohort (n = 101,799), the risk increase for MI per 1% (10 mmol/mol) increase in HbA 1c was higher for updated latest and updated mean HbA 1c of 1.11 (95% CI 1.09-1.13) and 1.15 (1.13-1.18) than for baseline HbA 1c of 1.05 (1.03-1.06). In the early subcohort, the corresponding risk estimates were greater than those in the recent subcohort. When categorized, the updated latest variable showed an increased risk for HbA 1c <6% (42 mmol/mol), relative category 6-7%, in the recent but not in the early subcohort, with hazard ratios of 1.23 (1.08-1.40) and 1.01 (0.84-1.22), respectively. CONCLUSIONSThe two time-updated HbA 1c variables show a stronger relation with MI than baseline HbA 1c . The risk association between HbA 1c and MI has decreased over time. In recently diagnosed patients with type 2 diabetes, an increased risk of MI exists at a current HbA 1c of <6.0% (42 mmol/mol).The global burden of diabetes has risen dramatically during the last two decades and is expected to affect more than 500 million adults worldwide by 2030, with the majority having type 2 diabetes (1). Patients with type 2 diabetes have a shorter lifeexpectancy, and myocardial infarction (MI) is the most common cause of the excess risk of death in these patients (2-4). Studies of glycemia as a risk factor for cardiovascular events have shown somewhat different results. Three large clinical trials,

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Section: Discussionsupporting

confidence: 76%

Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes

et al. 2015

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“…All forms of diabetes are clinically defined by increased blood glucose concentration and there is a progressive relationship between hyperglycemia and CVD, with CV risk rising approximately 20% for every 1.5 mM increase in fasting glucose levels [29], and for every 1% elevation in HbA1c levels [30]. Both epidemiological and pathophysiological studies have shown that hyperglycemia is an independent risk factor for CVD [6,31,32]. Hyperglycemia is known to increase flux through the HBP leading to increased production of UDP-N-acetylglucosamine (UDP-GlcNAc) - an essential substrate for both N-linked and O-linked protein glycosylation [33,34].…”

Section: Discussionmentioning

confidence: 99%

Glucosamine-induced ER Stress Accelerates Atherogenesis: A Potential Link between Diabetes and Cardiovascular Disease

Dang¹,

Beriault²,

Deng³

et al. 2015

J Mol Genet Med

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Background: Cardiovascular disease is the leading cause of death worldwide and is responsible for three out of four deaths in diabetic individuals. Our lack of understanding of the molecular mechanisms linking diabetes and atherosclerosis impedes the development of effective treatment strategies. Hyperglycemia and glucosaminesupplementation have been shown to induce endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) in murine models of atherosclerosis. We hypothesize that diabetes/hyperglycemia promotes atherosclerosis by a mechanism involving glucosamine-induced ER stress/UPR activation and that attenuation of ER stress, using the chemical chaperone 4-phenylbutyric acid (4PBA), will slow the accelerated development of atherosclerosis.

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“…The debate has continued because of the early cessation of the Action to Control Cardiovascular Risk for Diabetes (ACCORD) trial [12], because there was an increased mortality in the treatment group that included patients who were trying to achieve low HbA1c levels. Since 2008, a number of metaanalyses have been conducted on these clinical studies to highlight further the conflicting results [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…Provision of appropriate tables and graphics [18][19][20][21][22][23] See also other supplementary tables…”

mentioning

confidence: 99%

The HbA1c and All-Cause Mortality Relationship in Patients with Type 2 Diabetes is J-Shaped: A Meta-Analysis of Observational Studies

Arnold

Wang

2014

Rev Diabet Stud

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■ AbstractBACKGROUND: Low blood glucose and HbA1c levels are recommended in the literature on management of diabetes. However, data have shown that low blood glucose is associated with serious adverse effects for the patients and the recommendation has been criticized. Therefore, this article revisits the relationship between HbA1c and all-cause mortality by a meta-analysis of observational studies. AIM: The aim of this study is to determine whether there is a J-or Ushaped non-linear relationship between HbA1c and all-cause mortality in type 2 diabetes patients, implying an increased risk to premature all-cause mortality at high and low levels of HbA1c. METHODS: A comprehensive literature search was conducted using PubMed, Medline, and Cochrane Library databases with strict inclusion/exclusion criteria. The published adjusted hazard ratios (HR) with 95% confidence intervals of all-cause mortality for each HbA1c category and per study were analyzed. Fractional polynomial regression was used with random effect modeling to assess the nonlinear relationship of the HR trends between studies. Seven eligible observational studies with a total of 147,424 participants were included in the study. RESULTS: A significant Jshaped relationship was observed between HbA1c and allcause mortality. Crude relative risk for all-cause mortality identified a decreased risk per 1% increase in HbA1c below 7.5% (58 mmol/mol) (0.90, CI 0.86-0.94) and an increased risk per 1% increase in HbA1c above 7.5% (58 mmol/mol) (1.04, CI 1.01-1.06). Observational studies revealed a Jshaped relationship between HbA1c and all-cause mortality, equivalent to an increased risk of mortality at high and low HbA1c levels. CONCLUSIONS: This increased mortality at high and low HbA1c levels has significant implications on investigating optimum clinical HbA1c targets as it suggests that there are upper and lower limits for creating a 'security zone' for diabetes management.

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Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes: A meta-analysis

Abstract: An intensive glucose control strategy can effectively reduce the risk of major cardiovascular events but at the expense of a significantly increased risk of severe hypoglycemia in patients with type 2 diabetes.

Cited by 31 publications

References 32 publications

Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes

Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes

Glucosamine-induced ER Stress Accelerates Atherogenesis: A Potential Link between Diabetes and Cardiovascular Disease

The HbA1c and All-Cause Mortality Relationship in Patients with Type 2 Diabetes is J-Shaped: A Meta-Analysis of Observational Studies

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