Nonlipid plasma biomarkers are associated with incident diabetes mellitus in patients with CAD

Arsenault BJ, Kohli P, Lambert G, et al.
Am J Card 2016;29 Publication ahead of print

Background

Traditional type 2 diabetes mellitus (T2DM) risk factors, such as hypertension and obesity, as well as triglyceride and high-density lipoprotein cholesterol (HDL-c) levels are associated with T2DM risk in patients with coronary artery disease (CAD)[1]. It is also recently shown that plasma levels of some biomarkers of lipoprotein-lipid metabolism, inflammation and glucose-insulin homeostasis may predict cardiovascular disease (CVD) risk in statin-treated patients with CAD[2].

The objective of this study was to determine whether a panel of 18 biomarkers associated with the risk of CVD also predicted incident T2DM in statin-treated patients with CAD. Incident DM was
defined prospectively as at least 2 postbaseline fasting blood glucose measurements >7 mmol/L and at least 1 postbaseline fasting blood glucose measurement >2 mmol/L above baseline. Also patients for whom T2DM was noted through adverse event reporting, were included. After patient selection, biomarkers were measured in 1,424 patients.

Main results

At baseline, patients with incident T2DM and those who had T2DM at baseline:

• Had a significantly higher mean BMI (31.0/31.0 kg/m²), systolic blood pressure (133.9/135.3 mmHg) and prevalence of metabolic syndrome (77/83%) for incident T2DM/T2DM at baseline vs. 27.9 kg/m², 129.4 mmHg, 47% respectively for those who did not experience T2DM.
• Had significantly higher levels of triglycerides (154/162 mg/dL) and total cholesterol (180/176 mg/dL) and lower levels of HDL-c (46/44 mg/dL) for incident T2DM/T2DM at baseline vs. 133, 174, 48 mg/dL respectively for those whom did not experience T2DM.
• Had significantly higher total cholesterol/HDL-c ratio (4.09/4.12) for incident T2DM/T2DM at baseline vs. 3.80 for those who did not experience T2DM.
• Had significantly lower levels of total (5.19/6.12 µg/mL) and HMW adiponectin (1.45/1.80 µg/mL), Lp-PLA2 (310/305 ng/mL), soluble receptor of advanced glycation end products (1.22/1.33 ng/mL) and vitamin D (71.5/69.0 ng/mL) for incident T2DM/T2DM at baseline vs. 6.75 µg/mL, 2.02 µg/mL, 335 ng/mL, 1.34 ng/mL, 77.0 ng/mL respectively for those who did not experience T2DM.
• Had significantly higher levels of insulin (15/16 µU/mL), soluble CD40 ligand (5.69/4.13 ng/mL) and soluble intercellular adhesion molecule-1 (160/149 ng/mL) for incident T2DM/T2DM at baseline vs. 11 µU/mL, 3.87 ng/mL, 140 ng/mL respectively for those who did not experience T2DM.

After adjusting, using hazard ratio measurements the total and HMW adiponectin and Lp-PLA2 nonlipid biomarkers were negatively associated with risk for incident T2DM.

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Conclusion

Although several plasma biomarkers at baseline were associated with incident T2DM, only Lp-PLA2 and adiponectin remained independently associated with incident T2DM. Both markers need further investigation to determine their relation with T2DM.

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References

1. Waters DD, Ho JE, DeMicco DA, Breazna A, Arsenault BJ, Wun CC, Kastelein JJ, Colhoun H, Barter P. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol 2011;57:1535e1545.
2. Arsenault BJ, Barter P, DeMicco DA, Bao W, Preston GM, LaRosa JC, Grundy SM, Deedwania P, Greten H, Wenger NK, Shepherd J, Waters DD, Kastelein JJ; Treating to New Targets (TNT) Investigators. Prediction of cardiovascular events in statin-treated stable coronary patients of the treating to new targets randomized controlled trial by lipid and non-lipid biomarkers. PLoS One 2014;9:e114519.