Philadelphia University + Thomas Jefferson University

Diabetes, Heart Disease, and Mortality

Protein found that may be involved in the more lethal form of heart disease in type 1 diabetes.


Using  software called Ingenuity Pathway Analysis (IPA), the researchers examined what HMGCS2 normally does in the body. Although they found it was involved in ketone synthesis – a mechanism used by the liver to capture and store energy in ketone bodies, for later use by other organs – it was never explored in type 1 diabetes-related heart disease. Dr. Rafiq’s finding that HMGCS2 was more highly expressed in the heart of type 1 diabetic mice suggests that it may play a role in the development of heart disease as well.  

Further studies will be needed to better understand how HMGCS2 contributes to heart disease. “But this protein is a very promising and new lead for the field, especially in the area of altered energy metabolism in diabetes and heart disease” says Dr. Rafiq. “And of course, the study of HMGCS2 may lead to the identification of additional proteins in other biological pathways that play a role in the development of type 1 diabetes cardiovascular disease.”   

The research was supported by National Institutes of Health R01 grant (HL111278).

The authors have declared that no competing interests exist.

Article reference: Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq.  HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk. Scientific Reports 7:4590 DOI: 10.1038, 2017.

By Edyta Zielinkska