Elevated Liver Enzyme Linked With Poor Outcomes in Type 2 Diabetes
Key Takeaways
Higher levels of alkaline phosphatase (ALP), as well as variability in serum levels of ALP, are associated with increased risk of all-cause mortality, cardiovascular mortality, and new-onset heart failure in patients with type 2 diabetes.
ALP is an enzyme found in the liver, bone, bile duct, kidney, intestinal mucosa, and placenta (in women).
Determining the underlying mechanisms of these associations and validating the predictive value of ALP and its variability will require further study.
This study is currently a preprint and has not been peer-reviewed.
Why This Matters
Results from prior studies showed that elevated ALP levels are independently associated with an increased risk of adverse outcomes in patients with chronic kidney disease or a history of stroke, myocardial infarction, or percutaneous coronary intervention.
The present study aimed to evaluate the predictive value of ALP levels and variability in patients with type 2 diabetes for development of incident heart failure, cardiovascular death, and all-cause death.
According to the authors, this is the first study to investigate the possible association of new-onset heart failure with higher tertiles of ALP in patients with type 2 diabetes.
Study Design
Retrospective analysis of data from 14,289 patients with type 2 diabetes who presented to the Hong Kong Hospital Authority from January 1, 2000 to December 31, 2019.
The analysis excluded patients with fewer than three ALP measurements before they developed relevant outcomes.
The primary outcomes were new-onset heart failure, cardiovascular mortality, and all-cause mortality.
The analysis included incident outcomes through December 31, 2019.
Key Results
Over a mean follow-up of 2513 days (6.9 years), 10,182 patients (71%) died from any cause, 1966 patients (14%) died from cardiovascular causes, and 1171 patients (8%) developed new-onset heart failure.
The analysis divided patients into tertiles of baseline ALP levels: less than 72 U/L, 72-90 U/L, and greater than 90 U/L.
The cumulative incidences of all-cause death, cardiovascular death, and new-onset heart failure were each significantly higher in the tertile of patients with the highest ALP levels compared with patients in the middle- and low-ALP level tertiles.
In a multivariate model that adjusted for baseline differences in demographics, past comorbidities, and medications, patients in the tertile with the highest ALP levels had significantly increased rates of all-cause death (hazard ratio [HR], 1.32), cardiovascular death (HR, 1.22), and incident heart failure (HR, 1.35).
However, after further adjustment for subclinical biomarkers, the hazard ratios for all three outcomes were no longer significant.
Limitations
This observational study is susceptible to observational bias, including under-coding and coding errors.
The medical-records database used for this study did not include information on cardiovascular risk factors such as smoking and sedentary lifestyle.
Data on serum phosphorus, vitamin D, and parathyroid hormone levels were not available.
Echocardiographic data were unavailable, and hence, patients’ left ventricular ejection fraction was not known.
Disclosures
The preprint currently does not include a statement about the source of the study’s funding.
The authors have reported no relevant financial relationships.
This is a summary of a preprint research study written by a group of researchers based at various centers in the UK and China on MedRxiv provided to you by Medscape. This study has not yet been peer-reviewed. The full text of the study can be found on MedRxiv.org.
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