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A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative.

ABSTRACT: BACKGROUND:While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population. OBJECTIVE:We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women. METHODS:To test our hypothesis, we used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women's Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (<80mg/dL), normal/reference (80-99mg/dL), impaired (100-125mg/dL), and diabetic (?126mg/dL). RESULTS:Participants were free of cardiovascular disease at enrollment, had mean age of 62years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15years. Graphs of continuous incidence rates compared to fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. CONCLUSIONS:Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality.

SUBMITTER: Mongraw-Chaffin M

PROVIDER: S-EPMC5402725 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative.

Mongraw-Chaffin Morgana M LaCroix Andrea Z AZ Sears Dorothy D DD Garcia Lorena L Phillips Lawrence S LS Salmoirago-Blotcher Elena E Zaslavsky Oleg O Anderson Cheryl A M CA

Metabolism: clinical and experimental 20170216

<h4>Background</h4>While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population.<h4>Objective</h4>We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women.<h4>Methods</h4>To test our hypothesis, we used both continuous incidence r ...[more]

PMID: 28403935

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Project description:Aims/hypothesisThe aim of this study was to determine whether long-term intra-individual variability in fasting glucose (FG) during young adulthood is associated with incident diabetes, cardiovascular disease (CVD) and mortality.MethodsWe included participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 18-30 years at baseline (1985-1986) and followed with eight examinations for up to 30 years. Long-term glucose variability was assessed using the CV (CV-FG) and the absolute difference between successive FG measurements (average real variability; ARV-FG). For participants who developed any event (diabetes, CVD or mortality), FG variability measurement was censored at the examination prior to event ascertainment. We estimated HRs for incident diabetes, CVD and mortality with adjustment for demographics, baseline FG, change in FG (censor - baseline) and time-varying education, smoking, alcohol consumption, BMI, physical activity, systolic BP, BP medications, LDL-cholesterol and cholesterol medications (and incident diabetes and diabetes medications for CVD and mortality outcomes).ResultsAmong 3769 black and white participants, there were 317 incident diabetes cases (102,677 person-years), 159 incident CVD events (110,314 person-years) and 174 deaths (111,390 person-years). After adjustment, HRs per 1 SD higher ARV-FG were 1.64 (95% CI 1.52, 1.78) for diabetes, 1.15 (95% CI 1.01, 1.31) for CVD and 1.25 (95% CI 1.11, 1.40) for mortality. The HRs per 1 SD higher CV-FG were 1.39 (95% CI 1.21, 1.58) for diabetes, 1.32 (95% CI 1.13, 1.54) for CVD and 1.08 (95% CI 0.92, 1.27) for mortality, after adjustment. The cause-specific HRs per 1 SD higher ARV-FG were 1.29 (95% CI 1.14, 1.47) for non-CVD death and 1.05 (95% CI 0.76, 1.45) for CVD death. We did not observe evidence for effect modification of any association by sex or race.Conclusions/interpretationOur results suggest that higher intra-individual FG variability during young adulthood before the onset of diabetes is associated with incident diabetes, CVD and mortality.

Project description:AIMS/HYPOTHESIS:Evidence that glucose-dependent insulinotropic peptide (GIP) and/or the GIP receptor (GIPR) are involved in cardiovascular biology is emerging. We hypothesised that GIP has untoward effects on cardiovascular biology, in contrast to glucagon-like peptide 1 (GLP-1), and therefore investigated the effects of GIP and GLP-1 concentrations on cardiovascular disease (CVD) and mortality risk. METHODS:GIP concentrations were successfully measured during OGTTs in two independent populations (Malmö Diet Cancer-Cardiovascular Cohort [MDC-CC] and Prevalence, Prediction and Prevention of Diabetes in Botnia [PPP-Botnia]) in a total of 8044 subjects. GLP-1 (n?=?3625) was measured in MDC-CC. The incidence of CVD and mortality was assessed via national/regional registers or questionnaires. Further, a two-sample Mendelian randomisation (2SMR) analysis between the GIP pathway and outcomes (coronary artery disease [CAD] and myocardial infarction) was carried out using a GIP-associated genetic variant, rs1800437, as instrumental variable. An additional reverse 2SMR was performed with CAD as exposure variable and GIP as outcome variable, with the instrumental variables constructed from 114 known genetic risk variants for CAD. RESULTS:In meta-analyses, higher fasting levels of GIP were associated with risk of higher total mortality (HR[95% CI]?=?1.22 [1.11, 1.35]; p?=?4.5?×?10-5) and death from CVD (HR[95% CI] 1.30 [1.11, 1.52]; p?=?0.001). In accordance, 2SMR analysis revealed that increasing GIP concentrations were associated with CAD and myocardial infarction, and an additional reverse 2SMR revealed no significant effect of CAD on GIP levels, thus confirming a possible effect solely of GIP on CAD. CONCLUSIONS/INTERPRETATION:In two prospective, community-based studies, elevated levels of GIP were associated with greater risk of all-cause and cardiovascular mortality within 5-9 years of follow-up, whereas GLP-1 levels were not associated with excess risk. Further studies are warranted to determine the cardiovascular effects of GIP per se.

Project description:ImportanceHealth outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.ObjectiveTo examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.Design, setting, and participantsObservational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.InterventionsConjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).Main outcomes and measuresAll-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.ResultsAmong 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.Conclusions and relevanceAmong postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.Trial registrationclinicaltrials.gov Identifier: NCT00000611.

Dataset Information

A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative.

Publications

A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative.

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