Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Type 1 Diabetes and Heart Disease Linked by Inflammatory Protein

Published: Wednesday, May 08, 2013
Last Updated: Wednesday, May 08, 2013
Bookmark and Share
Therapeutic agents that block the protein calprotectin could potentially reverse or slow the progression of atherosclerosis in people with type 1 diabetes.

Type 1 (insulin-dependent) diabetes appears to increase the risk of heart disease, the leading cause of death among people with high blood sugar, partly by stimulating the production of calprotectin, a protein that sparks an inflammatory process that fuels the buildup of artery-clogging plaque. The findings, made in mice and confirmed with human data, suggest new therapeutic targets for reducing heart disease in people with type 1 diabetes. Led by Columbia University Medical Center (CUMC) researchers in collaboration with investigators at New York University and the University of Pittsburgh, the study was published today in the online edition of Cell Metabolism.

Diabetes is known to raise the risk for atherosclerosis, a disease in which fatty deposits known as plaque accumulate inside arteries. Over time, the arteries harden and narrow, leading to coronary artery disease and other forms of heart disease. Atherosclerosis is the leading cause of heart attacks, strokes, and peripheral vascular disease—collectively known as coronary heart disease, the leading cause of death in the United States.

Scientists have known that diabetes leads to atherosclerosis. The study shows that this is associated with increased circulating levels of inflammatory white blood cells (WBCs), which contribute to the build-up of plaque. “But exactly how diabetes causes white blood cells to proliferate and lead to heart disease has been a mystery,” said study co-leader Ira J. Goldberg, MD, the Dickinson W. Richards Professor of Medicine at CUMC.

In studies of mice with type 1 diabetes, Dr. Goldberg and his colleagues found that high blood sugar stimulates a type of inflammatory WBC known as neutrophils to release the protein calprotectin (also known as S100A8/9). The calprotectin travels to the bone marrow, where it binds to a cell-surface receptor called RAGE receptor, on common myeloid progenitor cells, which are involved in the production of various types of blood cells. This, in turn, leads to the proliferation of cells, known as granulocyte macrophage progenitor cells, which trigger the proliferation of even more neutrophils and of monocytes (another type of inflammatory WBC). Finally, these new WBCs enter the circulation and make their way to arterial plaques, fueling their progression.

The researchers also found that normalizing the mice’s blood glucose dampened this pathway, leading to an overall decrease in inflammation.

To determine the relevance of these findings in humans, the researchers analyzed data from 290 patients in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, led by EDC Principal Investigator Trevor J. Orchard, who has been following people with diabetes for 18 years. Total WBC, neutrophil, and monocyte counts were all significantly associated with the development of coronary artery disease. The researchers also analyzed blood samples from a subgroup of EDC patients. Those who had developed coronary artery disease had significantly higher levels of calprotectin, compared with patients who had not developed coronary artery disease.

“The human data appear to fit with the animal data, in that both WBCs and calprotectin are associated with heart disease,” said co-lead author Andrew J. Murphy, PhD, postdoctoral fellow in medicine at CUMC. The other lead author is Prabhakara R. Nagareddy, PhD, postdoctoral fellow at CUMC.

“Our findings point to the importance of controlling blood sugar levels to limit the production of the inflammatory cells that drive atherosclerosis; they also suggest novel therapeutic strategies, such as inhibiting the production of calprotectin or preventing its binding to the RAGE receptor,” said study co-leader Alan R. Tall, MD, the Tilden Weger Bieler Professor of Medicine at CUMC.

The CUMC team is currently studying how type 2 diabetes increases one’s risk for heart disease.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Major Complication of Parkinson’s Therapy Explained
Researchers have discovered why long-term use of ¬¬¬L-DOPA (levodopa), the most effective treatment for Parkinson’s disease, commonly leads to a movement problem called dyskinesia, a side effect that can be as debilitating as Parkinson’s disease itself.
Monday, September 14, 2015
An Innovative Algorithm to Decipher How Drugs Work Inside the Body
Researchers at Columbia University Medical Center (CUMC) have developed a computer algorithm that is helping scientists see how drugs produce pharmacological effects inside the body.
Friday, July 24, 2015
Neurons Controlling Appetite Made from Skin Cells
Cells provide individualized model for studying obesity and testing treatments.
Monday, March 02, 2015
Bone Stem Cells Shown To Regenerate Bone And Cartilage In Adult Mice
Cells could be exploited to treat osteoarthritis and osteoporosis.
Monday, January 19, 2015
Non-Gluten Proteins as Targets of Immune Response to Wheat in Celiac Disease
The results were reported online in the Journal of Proteome Research.
Thursday, December 18, 2014
Human Stem Cells Converted to Functional Lung Cells
Possibility of generating lung tissue for transplant using a patient’s own cells.
Thursday, December 05, 2013
New Link Between Obesity and Diabetes Found
Targeting a single enzyme that raises both sugar and insulin levels in the obese could prevent and treat diabetes.
Monday, November 25, 2013
Human Stem Cells Elucidate Mechanisms of Beta-Cell Failure in Diabetes
Mechanisms that impair insulin production in diabetes identified using a human stem cell model of Wolfram syndrome, a rare form of diabetes.
Thursday, November 14, 2013
Researchers Discover Cells that Restore Bladder’s Unique Lining
Finding that could lead to new ways to treat chronic bladder pain or to produce new tissue for patients with damaged bladders.
Tuesday, September 24, 2013
Trial Aims to Advance Prenatal Diagnosis of Genetic Defects
High-risk pregnant women being recruited for research on chromosomal abnormalities and incidence of birth defects, developmental delays.
Thursday, August 22, 2013
Is There a Role for Vitamins in Cancer Prevention?
According to recent national surveys, approximately 40 percent of U.S. adults take multivitamins/multiminerals.
Monday, August 12, 2013
DNA Robots Find and Tag Blood Cells
Researchers have created a fleet of molecular “robots” that can home in on specific human cells and mark them for drug therapy or destruction.
Thursday, August 08, 2013
Study Reveals Genes That Drive Brain Cancer
About 15 percent of glioblastoma patients could receive personalized treatment with drugs currently used in other cancers.
Tuesday, August 06, 2013
Key Molecular Pathways Leading to Alzheimer’s Identified
Research approach highlights potential therapeutic targets.
Thursday, July 25, 2013
New Genetic Cause of Pulmonary Hypertension Identified
Study finds druggable target for rare fatal lung disease.
Thursday, July 25, 2013
Scientific News
Michigan Researchers Use Raman Spectroscopy
inVia confocal Raman microscope used in the study of various childhood diseases.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Detecting HIV Diagnostic Antibodies with DNA Nanomachines
New research may revolutionize the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV.
Snapshot Turns T Cell Immunology on its Head
New research may have implications for 1 diabetes sufferers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
New Approach to Treating Heparin-induced Blood Disorder
A potential treatment for a serious clotting condition that can strike patients who receive heparin to treat or prevent blood clots may lie within reach by elucidating the structure of the protein complex at its root.
Horse Illness Shares Signs of Human Disease
Horses with a rare nerve condition have similar signs of disease as people with conditions such as Alzheimer’s, a study has found.
How a Molecular Motor Untangles Protein
Diseases such as Alzheimer’s, Parkinson’s and prion diseases, all involve “tangled” proteins.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos