New Research Indicates Long-Term Positive Effects of Intensive Blood Sugar Control on the Progression of Diabetic Retinopathy

retina with diabetic retinopathy

New diabetes and diabetic retinopathy research indicates that people with type 2 diabetes, who intensively controlled their blood sugar levels during the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Eye Study, cut their risk of diabetic retinopathy in half in a follow-up analysis, called the ACCORD Follow-on Eye Study (ACCORDION), which was conducted four years after stopping the intensive blood sugar control regimen required by the ACCORD Trial.

“This study sends a powerful message to people with type 2 diabetes who worry about losing vision,” said Dr. Emily Chew, study co-author and deputy director of the National Eye Institute’s Division of Epidemiology and Clinical Applications. “Well-controlled glycemia, or blood sugar level, has a positive, measurable, and lasting effect on eye health.”

Please note, however, that there are cautionary issues and unresolved causative factors related to the blood sugar (glycemic) control group in the original ACCORD study (discussed below) that readers should evaluate carefully and discuss with their physicians.

About the Research from Diabetes Care

This new diabetic retinopathy research, entitled Persistent Effects of Intensive Glycemic Control on Retinopathy in Type 2 Diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study, has been published in the July 2016 edition of Diabetes Care, a peer-reviewed journal published monthly by the American Diabetes Association (ADA). Diabetes Care is a journal for health care practitioners that is intended to increase knowledge, stimulate research, and promote better management of people with diabetes.

The authors are Emily Chew, MD, from the National Eye Institute; the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group; and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group.

Some Explanations and Terminology

The ACCORD Trial

The ACCORD Trial (2003-2009) involved 77 study sites across North America and enrolled 10,251 participants, all with type 2 diabetes. The purpose of the ACCORD Trial was to test three treatment strategies to reduce the risk of cardiovascular disease among people with longstanding type 2 diabetes: (1) maintaining near-normal blood sugar levels (intensive glycemic control); (2) improving blood lipid levels, such as lowering LDL “bad” cholesterol and triglycerides and raising HDL “good” cholesterol; and (3) lowering blood pressure.

[Editor’s note: The treatment phase of the glycemic (blood sugar) control portion of ACCORD had been planned to last 5.6 years but was stopped at 3.5 years, due to an increase in death among participants in the intensive glycemic control group. Analyses thus far have not determined a specific cause for these increased deaths. However, the benefits of intensive glycemic therapy must be weighed against the potential risks – most notably the increased risk of death observed in the ACCORD Trial.]

The ACCORD Trial Eye Study analyzed a subset of 2,856 Trial participants who had not received laser photocoagulation or vitrectomy for proliferative diabetic retinopathy and who had data from the beginning through year four of the study.

ACCORD was sponsored by the National Heart, Lung, and Blood Institute, with collaborators from the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; the National Eye Institute; and the Centers for Disease Control and Prevention. You can read more about the ACCORD Trial at The National Institutes of Health and Clinical

The ACCORDION Follow-on Eye Study

ACCORDION (2010-2014) is a follow-up assessment of diabetic retinopathy progression in 1,310 people who participated in ACCORD. ACCORDION re-assessed diabetic retinopathy approximately four years after the intensive glycemic control portion of the study had ended, and eight years after enrollment in ACCORD.

By that time, the average A1c (see explanation below) was 7.8 percent for the intensive therapy group and 7.9 percent for the standard therapy group. However, diabetic retinopathy had advanced in only 5.8 percent of participants in the intensive therapy group since enrollment in ACCORD, compared to 12.7 percent in the standard therapy group. ACCORDION was funded through the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Type 2 Diabetes

Type 2 diabetes (formerly called adult-onset, Type II, or non-insulin dependent) has the following characteristics:

  • It usually occurs after age 30 and affects 90%-95% of individuals with diabetes.
  • It occurs if (1) the pancreas does not produce enough insulin (insulin deficiency), (2) the body’s cells are not able to use insulin correctly and efficiently (insulin resistance), or (3) both conditions are present.
  • Glucose continues to rise in the bloodstream because sufficient levels of insulin are not available to open the cells and allow glucose to enter.
  • Initially, it can be managed with weight loss, physical activity, and effective meal planning. For some individuals this suffices for a period of time; when the disease progresses, however, oral medication or insulin may also be required.
  • Primary risk factors include increasing age (45+); ethnic background (African-American, Latino, Native American, Asian); family history; and obesity. You can learn more at What Is Diabetes?.

The A1c Test

The A1c blood test, also known as glycated hemoglobin, hemoglobin A1c, and HbA1c, is the primary tool used to diagnose diabetes and pre-diabetes and to monitor blood glucose control in people with type 1 and type 2 diabetes. This test enables health care providers to diagnose diabetes and treat it before complications occur and to diagnose pre-diabetes to prevent or delay the development of type 2 diabetes. You can read more about the established A1c levels used to diagnose diabetes and pre-diabetes at Diabetes and the Significance of the A1c Test.

About the Research

Excerpted from Intense diabetes treatment prevents damage to vision at United Press International:

Intense treatment of diabetes can help prevent damage to blood vessels in the retina that often leads to blindness, according to a long-term study by the National Institutes of Health. Researchers used aggressive treatment to maintain glycemic control, blood lipid levels and blood pressure, cutting the risk for developing diabetic retinopathy in half, they reported.

The researchers stopped the portion focused on glycemic control 3.5 years into a planned 5.6-year test because of an increase in death among participants, though patients being treated for blood pressure and blood lipid levels continued for the rest of the intended test period.

Tight control of the condition improved health of patients, but did not reduce risk for cardiovascular disease. The treatment did, however, reduce the progress of retinopathy by about one-third.

For the new study, the researchers re-examined 1,310 patients who took part in the original ACCORD study to measure the progression of participants’ retinopathy four years after treatment concluded. While measures of blood glucose between participants who received intensive and standard care remained similar to the end of the previous study, 5.8 percent of participants had seen advancement in their retinopathy – less than half the 12.7 percent of those receiving standard treatment whose condition progressed.

More about Diabetic Eye Disease

Diabetic Retinopathy

Although people with diabetes are more likely to develop cataracts at a younger age and are twice as likely to develop glaucoma as people who do not have diabetes, the primary vision problem caused by diabetes is diabetic retinopathy, the leading cause of new cases of blindness and low vision in adults aged 20-65:

NEI example of seeing with diabetic retinopathy: many blind spots and overall blurriness
What a person with diabetic retinopathy may see
  • “Retinopathy” is a general term that describes damage to the retina.
  • The retina is a thin, light-sensitive tissue that lines the inside surface of the eye. Nerve cells in the retina convert incoming light into electrical impulses. These electrical impulses are carried by the optic nerve to the brain, which interprets them as visual images.
  • Diabetic retinopathy occurs when there is damage to the small blood vessels that nourish tissue and nerve cells in the retina.
  • “Proliferative” is a general term that means to grow or increase at a rapid rate by producing new tissue or cells. When the term “proliferative” is used in relation to diabetic retinopathy, it describes the growth, or proliferation, of abnormal new blood vessels in the retina. “Non-proliferative” indicates that this process is not yet occurring.
  • Proliferative diabetic retinopathy affects approximately 1 in 20 individuals with the disease.

Four Stages of Diabetic Retinopathy

According to the National Eye Institute, diabetic retinopathy has four stages:

  • Mild non-proliferative retinopathy: At this early stage, small areas of balloon-like swelling occur in the retina’s tiny blood vessels.
  • Moderate non-proliferative retinopathy: As the disease progresses, some blood vessels that nourish the retina become blocked.
  • Severe non-proliferative retinopathy: Many more blood vessels become blocked, which disrupts the blood supply that nourishes the retina. The damaged retina then signals the body to produce new blood vessels.
  • Proliferative retinopathy: At this advanced stage, signals sent by the retina trigger the development of new blood vessels that grow (or proliferate) in the retina and the vitreous, which is a transparent gel that fills the interior of the eye. Because these new blood vessels are abnormal, they can rupture and bleed, causing hemorrhages in the retina or vitreous. Scar tissue can develop and can tug at the retina, causing further damage or even retinal detachment.

More about the Study from Diabetes Care

Condensed and excerpted from the article summary and conclusion, with the full article available online:

Our results showed that intensive glycemic control conferred enduring protection from progression of diabetic retinopathy even though the glycated hemoglobin levels were similar 8 years after randomization and about 4 years after the cessation of the clinical trial. This is the first study in people with type 2 diabetes of about 10 years’ duration and established cardiovascular disease, unlike the newly diagnosed participants in the United Kingdom Prospective Diabetes Study (UKPDS), that demonstrated this effect. This phenomenon has been called “metabolic memory” or “legacy effect” in the studies of type 1 diabetes.

The ACCORDION findings demonstrate a similar legacy effect of intensive glycemia control on the progression of retinal disease in people with established type 2 diabetes. Moreover, this effect occurred in response to a median of 3.7 years of intensive glycemic control, and was observed in people with type 2 diabetes and additional cardiovascular risk factors, whose mean diabetes duration was 10 years, and whose initial mean HbA1c was 8.2%.

These observations suggest that glucose lowering can reduce progression of retinal disease relatively late in the course of diabetes and that the retina responds to relatively short-term changes in glucose levels. Whether an even shorter period of glucose lowering could achieve a similar long-term effect on the eyes in either type 2 or type 1 diabetes remains unknown.

In summary, our study results provide evidence that intensive glycemic control is beneficial for reducing the progression of diabetic retinopathy and that the legacy effect is evident in people with type 2 diabetes. The addition of the ACCORDION retinal results to these prior findings demonstrates a posttreatment benefit of intensive glycemia control on the progression of eye, kidney, and nerve disease.

Additional Information