Synergism of Inflammatory Protein Markers and the Effect on Mortality in Patients with Type 2 Diabetes 

Certain inflammatory biomarkers may help lead to improvements in the treatment of type 2 diabetes: hs-CRP and serum Amyloid P components can predict all-cause mortality. 

As one of the leading causes of death worldwide, type 2 diabetes will become even more burdensome in the near future if not approached aggressively. To combat this, it is important to be able to identify patients at the highest risk for developing type 2 diabetes and use prevention strategies against it. One way to do so is to use novel biomarkers. Biomarkers improve risk stratification and may also be useful in pointing out pathogenic pathways that are still unknown that could potentially be the target of novel treatments. The objective of this study was to discover novel biomarkers capable of identifying high-risk patients who could be exposed to more aggressive preventative and treatment strategies. Researchers specifically explored hs-CRP and serum amyloid P component, two acute inflammation proteins, and their combined role in improving prediction of mortality in type 2 diabetes.  

There are no previous studies on the combined role of CRP and serum amyloid P on clinical events related to acute-phase inflammation and atherosclerosis. This study is the first contribution to this specific topic. Researchers of this study combined the two acute inflammation proteins and assessed the mortality rate in patients with type 2 diabetes. Then, the extent to which these biomarkers improve the prediction of all-cause death when added on top of prediction models of mortality risk in type 2 diabetes was evaluated.  

This study consisted of four cohorts of patients with type 2 diabetes. Three were from Apulia, central-southern Italy, and one from Tuscany, central Italy. The Gargano Heart Study prospective design was comprised of 368 patients with type 2 diabetes and coronary artery disease. These patients were recruited from 2001 to 2008 at the Endocrine Unit of Fonadazione and were followed yearly until 2011 for both cardiovascular and all-cause mortality. For the two acute inflammation proteins, 358 participants were assessed which was eligible for a sample in this analysis. The Foggia Mortality study was comprised of 1,115 patients that were recruited from the Endocrine Unit of the University of Foggia in central-southern Italy from 2002 to 2008. The two inflammation proteins were assessed in 530 participants that were eligible for analysis. The Pisa Mortality Study was comprised of 961 participants that were recruited from the Endocrine Unit of the University of Pisa in central Italy from 2002 to 2008. The two inflammation proteins were assessed in all 961 participants.  

For statistical analysis, unadjusted and adjusted Cox proportional hazard models were used in each study. These models assessed the association between hs-CRP and serum amyloid P levels, both singly and in a combined fashion, and all-cause mortality. All risks were reported as hazard ratios with confidence intervals as 95% per 1 standard deviation increase.  

While analyzing the results, researchers found that both hs-CRP and serum amyloid P were independently associated with all-cause mortality. For hs-CRP, the hazard ratio was 1.46, confidence interval of 1.34 to 1.58, and p-value <0.001. For serum amyloid P, the hazard ratio was 0.82, confidence interval of 0.76 to 0.89, and p-value <0.001. The results showed that there was an increased risk of death in patients with a serum amyloid P level < 33 mg/L versus those with a level >33 mg/L only if the hs-CRP was relatively high at > 2 mg/L. Researchers were able to determine that the addition of the two inflammatory proteins had a significant improvement in several discrimination and reclassification measures of both ENFORCE and RECODe all-cause mortality prediction models.  

In conclusion, the severity of type 2 diabetes’ effect on all-cause mortality is an important issue that needed to be addressed promptly. Researchers of this study were able to use two inflammatory protein markers, to show opposite and synergistic associations with all-cause mortality. There is a possibility that in the future, the combination of these two and others might further improve the ability to predict the risk of death in real-life settings.  

Practice Pearls: 

• hs-CRP and serum Amyloid P components can predict all-cause mortality in patients with type 2 diabetes. 
• The results of the study were statistically significant and show promise for future use. 
• The synergistic approach in fact does prevent mortality in patients with type 2 diabetes. 

Scarale, Maria Giovanna, et al. “The Synergic Association of Hs-CRP and Serum Amyloid P Component in Predicting All-Cause Mortality in Patients With Type 2 Diabetes.” Diabetes Care, June 2020, p. dc192489., doi:10.2337/dc19-2489. 

Deonna Andrews, PharmD Candidate 2020 of Florida Agricultural & Mechanical University College of Pharmacy and Pharmaceutical Sciences 

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