According to CDC estimates, almost 24 million people-nearly 8% of the population-have diabetes. For those diagnosed with Type 1 diabetes, complications resulting from the body's inability to produce insulin include heart disease, blindness (retinopathy), nerve damage (neuropathy) and kidney damage (nephropathy).

Researchers at the Harold Hamm Oklahoma Diabetes Center in Oklahoma City, OK, have found a way to stop the damage caused by Type 1 diabetes by using a combination of insulin and vitamin C. While neither therapy produced desired results when used alone, the combination of insulin to control blood sugar together with the use of vitamin C stopped blood vessel damage caused by the disease in patients with poor glucose control. The findings appear in the June issue of Journal of Clinical Endocrinology and Metabolism.

"We had tested this theory on research models, but this is the first time anyone has shown the therapy's effectiveness in people," said Michael Ihnat, PhD, principal investigator and a pharmacologist at the Oklahoma University College of Medicine Department of Cell Biology. "There is a huge body of knowledge on oxidative stress and diabetic complications. We (and others) had previously shown that oxidative stress persists after glucose levels in cells in culture and in diabetic animals [and] we wished to test this idea in type 1 diabetic patients."

The goal of the work being done by Dr. Ihnat and British scientists from the University of Warwick (led by Dr. Antonio Ceriello) was to find a way to stop the damage to blood vessels that is caused by diabetes. The damage, known as endothelial dysfunction, is associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes and chronic renal failure.

By reducing or stopping the damage, patients with diabetes could avoid some of the painful and fatal consequences of the disease that include heart disease, reduced circulation and amputation, kidney disease and diabetic retinopathy, which can lead to blindness.

Insulin and many other drugs have long been used to control blood sugar, but Dr. Ihnat-in an earlier project with scientists in Italy and Hungary – found that cells have a "memory" that causes damage to continue even when blood sugar is controlled. By adding antioxidants like vitamin C, Dr. Ihnat found that cell "memory" disappeared and cell function and oxidation stress were normalized.

"Many clinical studies have pointed toward oxidative stress propagating this 'metabolic memory' but had yet to be tested directly," Dr. Ihnat explained. "We have speculated that this happens with endothelial dysfunction, but we did not know until now if it was effective in humans. We finally were able to test it and proved it to be true.

"For patients with diabetes, this means simply getting their glucose under control is not enough," he continued. "An antioxidant-based therapy combined with glucose control will give patients more of an advantage and lessen the chance of complications with diabetes."

Study Details

In the study, 10 healthy subjects and three subgroups of 10 Type 1 diabetic subjects were enrolled and categorized according to the amount of time since diagnosis.

Each patient participated in three experiments: 24 hour insulin treatment, achieving a near-normalization of glycemia, together with the addition of the antioxidant vitamin C during the last 12 hours; 24 hours vitamin C treatment with insulin treatment for the last 12 hours; and treatment with both vitamin C and insulin for 24 hours.

Researchers found that endothelial function, as measured by flow-mediated vasodilation (FMD) of the brachial artery and levels of nitrotyrosine, an oxidative stress marker, were normalized by each treatment in subgroups 1 and 2. In the third subgroup, neither glucose normalization nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C, however, normalized endothelial dysfunction and nitrotyrosine.

While researchers do suggest diabetic patients eat foods and take multivitamins rich in antioxidants like vitamin C, they warned that additional study is needed. The vitamin C utilized in their study was given at very high doses and administered directly into the bloodstream, making it unlikely that similar results could be reproduced with an over-the-counter vitamin supplement. "Remember, we gave the vitamin C through IV which is not yet possible through pumps, etc We seriously doubt even large amounts of oral vitamin C would have the same effect and right now the best we can suggest is for patients to consult their physician before beginning antioxidant therapy," said Dr. Ihnat.

He added that vitamin C isn't the only inherently appropriate antioxidant to pair with insulin for the purpose of staving off this type of blood vessel damage. "In my opinion, many other antioxidants will do the same thing if you can get enough of them to the target sites (which is a very tall order)," he said.

The team is currently trying to learn how oxidative stress persists and working to determine how antioxidants function at the molecular level to halt the destructive chain reaction set in motion by high blood sugar levels. In addition, they are evaluating several other antioxidants with an ultimate hope that their work will translate into simple, effective and inexpensive treatments for the control of diabetes.

"We plan to replicate these studies with more patients, with type 2 diabetic patients, with other antioxidants," concluded Dr. Ihnat.