A study of patients with acute coronary syndrome and persistent dyslipidemia shows that despite intensive or maximum tolerated statin treatment, lower levels of lipoprotein(a) may indeed increase the risk of type 2 diabetes despite the absence of type 2 diabetes.

Previously, observational data suggested that lower levels of lipoprotein(a) could be associated with a greater prevalence of type 2 diabetes, but whether using medicines to lower lipoprotein(a) would influence the incident type 2 diabetes wasn’t quite known.

So in this study, led by Gregory G. Schwartz, MD, a cardiologist with the University of Colorado School of Medicine, Aurora, researchers conducted a post hoc analysis of the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) (NCT01663402) that compared the use of the PCSK9 inhibitor alirocumab against a placebo group of 18,924 patients with recent acute coronary syndrome and persistent dyslipidemia.


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The analysis by Schwartz et al., which was published in Diabetes Care, included 13,480 patients without diabetes at baseline, but over 2.7 years, 1,324 developed type 2 diabetes. At baseline, the average lipoprotein(a) level was 21.9 mg/dL. For the placebo group, a 10 mg/dL baseline lipoprotein(a) was associated with a hazard ratio of 1.04 (95% CI 1.0221.06, P < 0.001) for incident type 2 diabetes.

For patients who received alirocumab, lipoprotein(a) was reduced by an average of 23.2%, but it did not have an overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). For patients with low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while alirocumab treatment for patients with a high baseline lipoprotein(a) tended to increase incident type 2 diabetes as compared to placebo group. In the alirocumab treatment group, having a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with a hazard ratio 1.07 (95% CI 1.0321.12; P 5 0.0002) for incident type 2 diabetes.

The findings show that not only is baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes in patients with acute coronary syndrome, but overall, alirocumab had a neutral effect on whether patients would develop type 2 diabetes.

The authors highlighted three key insights into the relationship between lipoprotein(a) levels and the risk of type 2 diabetes. First, incident type 2 diabetes in the placebo group increased when baseline lipoprotein(a) was decreased, which confirms previous “observations in healthy populations and demonstrating this for the first time in a cohort with established atherosclerotic cardiovascular disease receiving intensive or maximum tolerated statin treatment.”

Secondly, alirocumab treatment does modify the relationship between baseline lipoprotein(a) concentration and incident type 2 diabetes. When lipoprotein(a) concentrations were low at baseline, alirocumab had a nuetral effect on lipoprotein(a) levels and there was evidence suggesting it reduced the risk of incident type 2 diabetes in this group. The opposite was found to be true as well:  High baseline lipoprotein(a) levels and alirocumab treatment reduced lipoprotein(a) concentrations in greater numbers and tended to increase the risk of type 2 diabetes in the treatment group.

And, finally, for the alirocumab treatment group, with each 10 mg/dL decrease in lipoprotein(a) from baseline through four months, there was a significant hazard ratio for incident type 2 diabetes after adjusting for variables, baseline lipoprotein(a), and the concurrent change from baseline in LDL-C corrected. “This finding suggests that treatment induced reduction in lipoprotein(a) concentration may increase the risk of incident type 2 diabetes,” the authors wrote.

Among the limitations the authors described for this study, included the effect of alirocumab on incident type 2 diabetes was observed on a background of intensive statin treatment, but whether alirocumab had an effect on statin treatment or had an independent effect on the risk of incident diabetes could not be determined.

Reference

Collyns OJ, Meier RA, Betts ZL, et al. Improved glycemic outcomes with Medtronic MiniMed advanced hybrid closed-loop delivery: Results from a randomized crossover trial comparing automated insulin delivery with predictive low glucose suspend in people with type 1 diabetes. Diabetes Care. 2021;44(4):969-975. doi:10.2337/dc20-2250