Diabetes and Heart Problems: Analyzing the Connection

It’s an unfortunate fact, but one that bears repeating ‒ the number of diabetics in the United States has exploded over the last few decades. The Centers for Disease Control and Prevention (CDC) reports that the number of Americans with diabetes rose dramatically from 1980 through 2011, soaring from 5.6 to 20.9 million cases. In addition to the symptoms caused directly by diabetes, researchers have also found that this condition may have an adverse impact on the heart.

The Multiple Forms of Diabetes

In short, diabetes is a condition in which the body suffers from the effects of high levels of blood sugar, or glucose. The three common forms of this condition are known as type 1 diabetes, type 2 diabetes and gestational diabetes. Originally referred to as juvenile diabetes, type 1 diabetes occurs when the pancreas fails to produce insulin, a hormone which enables cells to utilize glucose. Consequentially, glucose begins to accumulate within the body’s bloodstream. If not properly addressed, type 1 diabetes can eventually affect the eyes, teeth, nervous system, kidneys and heart.

Type 2 diabetes is by far the most prominent form of diabetes in the United States. It is estimated that 90 to 95 percent of all US diabetics have this illness. A person develops type 2 diabetes for one of two reasons; either the pancreas’ insulin production falls short of the body’s needs, or the body itself is unable absorb insulin. The latter issue is known as insulin resistance. Like its less common counterpart, type 2 diabetes can lead to serious complications if poorly treated. Problems associated with this condition include chest pains, narrowed arteries and nerve damage, along with deteriorating eyesight and hearing.

Finally, gestational diabetes afflicts only pregnant women. In most cases, this issue occurs during the latter half of a pregnancy. Medical researchers are still not exactly sure of the root causes behind gestational diabetes, though it is believed that the baby’s placenta might play a significant factor. While a fetus is growing in the womb, the placenta manufactures certain hormones which disrupt the body’s ability to absorb insulin.

Fortunately, most mothers-to-be with this complication successfully give birth to healthy children. However, such women are more likely to eventually develop type 2 diabetes. Moreover, children born to mothers with gestational diabetes face a greater threat from both type 2 diabetes and obesity.

Damaging the Heart

The American Heart Association (AHA) is very clear about the threat diabetes poses to the heart. In fact, this organization counts diabetes as one of seven major manageable risk factors for cardiovascular disease. The AHA also notes that this condition is two to four times more likely to strike diabetics than their non-diabetic counterparts.  

Many diabetics fall victim to cardiovascular disease (CVD) due to the presence of other medical problems:

• Obesity
• Sedentary lifestyle
• Habitual smoking
• Unhealthy levels of cholesterol and triglycerides
• Abnormally high blood pressure
• High glucose readings

Sugar Molecules and Proteins

A closer look at the diabetes-CVD connection was recently provided by the University of California, Davis, Health System. This study, which appeared on the journal Nature’s website in September 2013, argued that a specific biological pathway may connect these two conditions (the National Human Genome Research Institute defines a biological pathway as “a series of actions among molecules in a cell that leads to a certain product or a change in a cell”).

Aided by researchers from Johns Hopkins University, the UC Davis team conducted experiments involving tissues and proteins. These samples came from both human and rat donors. In addition, the authors also performed calcium imaging on rat heart muscle cells, which had been subjected to high amounts of glucose. Finally, the researchers used optical mapping technology to document heart arrhythmias (irregular heart beats) in living diabetic rats and isolated hearts.

Using this approach, the authors noticed that the behavior of a certain sugar molecule in heart cells was influenced by moderate to high levels of glucose. The molecule was identified as O-GlcNAc, or O-linked N-acetylglucosamine. Under such circumstances, these sugar molecules would attach themselves to a specific area of CaMKII, a protein that helps enable the heart to operate in a normal manner. The authors noted that heart’s calcium levels, electrical activity and pumping motions are all affected by this protein.

After the O-GlcNAc molecules fused with CaMKII proteins, the study found that the latter became overly active. In turn, the calcium signaling system controlled by CaMKII began to malfunction. Within the span of a few minutes, this biological reaction induced full-fledged arrhythmias.

The irregular heart beats caused by this interaction could be prevented, however, by suppressing the functions of CaMKIIs. The research team was also able to achieve this goal by keeping O-GlcNAc molecules from binding with CaMKII proteins.

A separate experiment added more evidence to the possible link between diabetes and heart disease. For this endeavor, the research team examined hearts and brains from deceased human diabetics. Unusually high levels of O-GlcNAc-modified CaMKII were observed in these organs. Donors who had been diagnosed with both diabetes and heart disease had the highest amount of O-GlcNAc/CaMKII fusions.

The authors of this study contend that their work could help doctors protect the hearts of diabetes sufferers. In a UC Davis press release, senior study author Donald Bers stated that “The novel molecular understanding we have uncovered paves the way for new therapeutic strategies that protect the heart health of patients with diabetes. While scientists have known for a while that CaMKII plays a critical role in normal cardiac function, ours is the first study to identify O-GlcNAc as a direct activator of CaMKII with hyperglycemia.” Bers further mentioned that the team will next attempt to unearth a similar relationship between O-GlcNAc, CaMKII and damage to the areas of the nervous system.