Visit-to-Visit Glycemic Variability and Risks of Cardiovascular Events and All-Cause Mortality: The ALLHAT Study

Echouffo‐Tcheugui, Justin B.; Zhao, Songzhu; Brock, Guy; Matsouaka, Roland; Kline, David; Joseph, Joshua J.

doi:10.2337/dc18-1430

Cited by 117 publications

(111 citation statements)

References 37 publications

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“…To minimize the bias caused by a single measurement of fasting glucose level, we used the mean fasting glucose level measured in both 2009-2010 and 2011-2012. Furthermore, glycemic variability, a strong predictor of CV events [27][28][29][30], could not be assessed because of the limited instance of fasting glucose measurements, in the present study. Third, the controlled fasting glucose levels during the future follow-up period could not be predicted.…”

Section: Discussionmentioning

confidence: 93%

The sweet spot: fasting glucose, cardiovascular disease, and mortality in older adults with diabetes: a nationwide population-based study

Lee

Han

Huh

2020

Cardiovasc Diabetol

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Background: Growing evidences shows that fasting glucose target should be different according to their health condition in older adults with diabetes. However, there are limited data regarding the relationship between fasting glucose level and health outcomes in Korean older people with diabetes. We aimed to examine the association of fasting glucose with mortality and cardiovascular events in Korean older adults with type 2 diabetes. Methods:From the Korean National Health Insurance System, 227,938 subjects (aged ≥ 65 years) with type 2 diabetes but no history of cardiovascular events (myocardial infarction or stroke) who underwent ≥ 2 health examinations from 2009 to 2010 and who were followed up until 2017 were identified. The primary exposure variable was the mean fasting glucose level. We estimated the relationship between the baseline fasting glucose level and incidences of allcause death and cardiovascular events. Comorbidity load was assessed using the Charlson comorbidity index. Results:Fasting glucose levels and all-cause mortality risk showed a J-shaped relationship regardless of sex and number of comorbidities. Fasting glucose levels associated with the lowest mortality and cardiovascular events were 110-124 and 95-124 mg/dL, respectively. Stratified analysis by comorbidity load using the Charlson comorbidity index revealed higher optimal fasting glucose levels for the lowest cardiovascular events in subjects with Charlson comorbidity index ≥ 3 than in those with Charlson comorbidity index ≤ 2 (119 vs. 112 mg/dL, P = 0.04).Conclusions: J-shaped relationship existed between fasting glucose and all-cause mortality and cardiovascular events in Korean older adults with diabetes. We identified that fasting glucose levels associated with the lowest mortality and cardiovascular events were 110-124 and 95-124 mg/dL respectively. Increased risk of cardiovascular events with low fasting glucose level (< 95 mg/dL) was noted, especially in patients with high comorbidity. These findings suggested that less stringent targets of fasting glucose may be beneficial especially in older adults with multiple comorbidities.

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Section: Discussionmentioning

confidence: 93%

The sweet spot: fasting glucose, cardiovascular disease, and mortality in older adults with diabetes: a nationwide population-based study

Lee

Han

Huh

2020

Cardiovasc Diabetol

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“…Mounting evidence demonstrates that glucose variability is associated with cardiovascular complications, particularly cardiovascular death (2-5), not only in diabetes but also in people without diabetes (10)(11)(12), and our study adds to this body of evidence. At the same time, SGLT-2 inhibitors, including empagli ozin, reduce glucose variability in both type 2 and type 1 diabetes (13)(14)(15).…”

Section: Discussionmentioning

confidence: 59%

Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial

Ceriello¹,

Ap²,

Zwiener³

et al. 2020

Preprint

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Background: Glucose variability has been associated with cardiovascular (CV) outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and CV death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of CV death by 38%. We explore post-hoc the association between HbA1c variability and CV death, and the potential mediating effects of HbA1c variability on empagliflozin’s CV death reductions.Methods: In total, 7,020 patients with type 2 diabetes and established CV disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between CV death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.Results: HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for CV death in both treatment arms with no interaction with treatment.Conclusions: HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of CV death. Empagliflozin’s reduction in CV death did not appear to be mediated by reductions in HbA1c variability.ClinicalTrials.gov number, NCT01131676. Registered May 27 2010. https://clinicaltrials.gov/ct2/show/NCT01131676

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“…The detailed description of the calculation of various FPG variability indices has been reported in previous publication. 17 definitions GDM was defined as the presence of more than four times of claim of GDM (ICD-10 O24.4 and O24.9) or prescription of insulin under the ICD-code of GDM. In South Korea, the "two-step" approach with a 50 g screen followed by a 100 g oral glucose tolerance test for those who screen positive is mainly used for the diagnosis of GDM.…”

Section: Materials and Methods Data Sourcementioning

confidence: 99%

Association of fasting plasma glucose variability with gestational diabetes mellitus: a nationwide population-based cohort study

Kim

Roh

et al. 2020

BMJ Open Diab Res Care

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ObjectiveLong-term glycemic variability has recently been recognized as another risk factor for future adverse health outcomes. We aimed to evaluate the risk of gestational diabetes mellitus (GDM) according to the prepregnancy long-term fasting plasma glucose (FPG) variability.Research design and methodsA total of 164 053 women who delivered their first baby between January 1, 2012 and December 31, 2015, were selected from the Korean National Health Insurance data. All women underwent at least three national health screening examinations, and the last examination should be conducted within 2 years before their first delivery. GDM was defined as the presence of more than four times of claim of GDM (International Classification of Disease, 10th Revision (ICD-10) O24.4 and O24.9) or prescription of insulin under the ICD-code of GDM. FPG variability was assessed by variability independent of the mean (FPG-VIM), coefficient of variation, SD, and average successive variability.ResultsAmong the 164 053 women, GDM developed in 6627 (4.04%). Those in the higher quartiles of FPG-VIM showed a stepwise increased risk of GDM. In fully adjusted model, the ORs for GDM was 1.22 (95% CI 1.14 to 1.31) in women with the highest FPG-VIM quartile compared with those in the lowest quartile. The risk for GDM requiring insulin therapy was 48% increase in women in the highest quartile of FPG-VIM compared with those in the lowest quartile, while that for GDM not requiring insulin therapy was 19% increase. The association between high FPG variability and the risk of GDM was intensified in the obese and aged more than 35 years women.ConclusionsIncreased FPG variability in the prepregnancy state is associated with the risk of GDM independent of confounding factors. Therefore, prepregnancy FPG variability might be a surrogate marker of the risk of GDM.

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Visit-to-Visit Glycemic Variability and Risks of Cardiovascular Events and All-Cause Mortality: The ALLHAT Study

Cited by 117 publications

References 37 publications

The sweet spot: fasting glucose, cardiovascular disease, and mortality in older adults with diabetes: a nationwide population-based study

The sweet spot: fasting glucose, cardiovascular disease, and mortality in older adults with diabetes: a nationwide population-based study

Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial

Association of fasting plasma glucose variability with gestational diabetes mellitus: a nationwide population-based cohort study

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