Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study

Anand, Sridhar; Gr, Dagenais; Mohan, V.; Dı́az, Rafael; Probstfield, Jeffrey L.; Freeman, Rosario V.; Shaw, Jonathan E.; Lanas, Fernando; Avezum, Álvaro; Budaj, Andrzej; Jung, Hyun Suk; Desai, Dipika; Bosch, Jackie; Yusuf, Salim; Gerstein, Hertzel C.

doi:10.1177/1741826711409327

Cited by 88 publications

(74 citation statements)

References 35 publications

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“…[1][2][3][4][5][6][7] Basal insulin secretion is required to maintain fasting plasma glucose levels below 100 mg per deciliter (5.6 mmol per liter), and an elevated fasting plasma glucose level indicates that there is insufficient endogenous insulin secretion to overcome underlying insulin resistance. 8,9 The correction of this deficiency may reduce cardiovascular outcomes.…”

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confidence: 99%

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

et al. 2012

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BACKGROUND: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. METHODS: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of 95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. RESULTS: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 personyears, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97). CONCLUSIONS: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

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confidence: 99%

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

et al. 2012

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“…[1][2][3][4] Moreover, despite recent reductions in the incidence of CV outcomes in people with diabetes mellitus, both diabetes mellitus and lesser degrees of dysglycemia remain independent CV risk factors. [5][6][7] The pathophysiologic reasons for this excess and for variations in incidence among people who already have established dysglycemia remain unclear.…”

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confidence: 99%

Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia

et al. 2015

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Background-Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome or death when added to clinical measurements. Methods and Results-A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 mL of stored frozen serum from every participant who provided biobanked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward-selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) allcause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71 and 0.68 for the 2 CV composite outcomes, respectively, with the greatest increase to 0.75 for death (P<0.001 for the change). Conclusions-

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“…Studies carried out in the general population show the predictive capacity of the tolerance test for cardiovascular events and mortality [21,22] and the OGTT has been used to diagnose DM [10,11]. However, evidence about the prognostic information provided by the tolerance test in ischemic patients after percutaneous coronary revascularization is scarce.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is accepted as a valid option for the diagnosis of diabetes, glycated hemoglobin (HbA 1c ), when used in isolation, may give incorrect results under certain conditions, which is why recommendations are fundamentally based on carrying out an oral glucose tolerance test (OGTT) [7,9]. For the diagnosis of diabetes, the OGTT is a more sensitive and better predictor of CVD than fasting glucose [9][10][11]. Nevertheless, despite being the best tool available, it does not wholly fulfil the characteristics of speed, simplicity, and reproducibility that are desirable in every screening test, and in habitual clinical practice guidelines are rarely followed.…”

Section: Introductionmentioning

confidence: 99%

Newly impaired glucose metabolism and prognosis after percutaneous revascularization

et al. 2015

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(OR = 2.70, p = 0.029) and readmission due to heart failure during the followup (OR = 3.82, p = 0.022). Conclusions: Screening for impaired glucose metabolism after PCI permits the detection of a high proportion of patients with abnormal glucose regulations. However, previously known diabetes remains the only independent predictor of cardiovascular events in the followup. (Cardiol J 2015; 22, 1: 44-51)

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Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study

Cited by 88 publications

References 35 publications

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia

Newly impaired glucose metabolism and prognosis after percutaneous revascularization

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