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Low, variable HDL cholesterol level creates ‘additive effect’ for diabetes risk
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Korean adults with a variable and overall lower HDL cholesterol level are significantly more likely to develop type 2 diabetes over 5 years when compared with adults with a higher HDL cholesterol level with less fluctuation, according to a large database analysis published in The Journal of Clinical Endocrinology & Metabolism.
“Previous studies have shown that there is a bidirectional relationship between low HDL cholesterol and glucose intolerance,” Seung-Hwan Lee, MD, PhD, a professor in the division of endocrinology and metabolism at St. Mary’s Hospital and the Catholic University of Korea in Seoul, South Korea, told Endocrine Today. “With this study, we add that HDL cholesterol variability, or a fluctuation in visit-to-visit HDL cholesterol levels, is a novel risk factor for incident diabetes.”
In a population-based study, Lee and colleagues analyzed data from 5,114,735 adults without known diabetes who underwent a health exam in 2012 and 2013 (index year) and at least two health exams in the preceding 3 years, using data from the National Health Insurance system in South Korea. Researchers calculated visit-to-visit HDL cholesterol variability using the variability independent of the mean (VIM) and coefficient of variation. Low mean and high variability groups were defined as the lowest and the highest quartile of HDL cholesterol mean and variability, respectively. Primary outcome was incident diabetes, based on at least one claim code per year for the prescription of a diabetes medication.
During a median follow-up of 5.1 years, researchers observed 122,192 cases (2.4%) of incident diabetes. Within the cohort, 12.6% of adults had high HDL cholesterol variability only, 12.2% had low mean only and 12.5% had both high variability and low mean. Those with high mean HDL cholesterol and low variability tended to be younger and less obese and had lower blood pressure vs. other groups, the researchers noted.
Researchers found that lower mean or higher variability of HDL cholesterol was associated with higher risk for diabetes in a stepwise manner, and an “additive effect” of the two measures was noted.
In a model adjusted for age, sex, BMI, alcohol intake, smoking status, physical activity, hypertension and use of lipid-lowering agents, the HRs for incident diabetes were 1.2 (95% CI, 1.18-1.22) in the high mean/high VIM group, 1.35 (95% CI, 1.33-1.37) in the low mean/low VIM group and 1.4 (95% CI, 1.38-1.42) in the low mean/high VIM group compared with the high mean/low VIM group.
Researchers observed similar results in models adjusting for waist circumference instead of BMI, those using coefficient of variation and in subgroup analyses. Results further persisted in sensitivity analysis designed to account for reverse causation, excluding adults with a diabetes diagnosis within 3 years of follow-up.
“Maintaining high HDL cholesterol levels with less fluctuation might help in reducing the risk of diabetes,” Lee said. “A prospective study is needed for the confirmation of a causal relationship. Appropriate measures to elevate and stabilize HDL cholesterol levels should be further investigated, as should underlying mechanisms.” – by Regina Schaffer
For more information:
Seung-Hwan Lee, MD, PhD, can be reached at the Catholic University of Korea, #10 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea; email: hwanx2@catholic.ac.kr.
Disclosures: The authors report no relevant financial disclosures.
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