Landmark Studies in Diabetes Care

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Landmark Studies in Diabetes Care

Dr. Rita Kalyani

Contributor:
Dr. Rita Kalyani, MD, MHS

In the past 25 years, several large research studies in persons with prediabetes and diabetes have led to a great deal of important, scientifically supported information. These studies have shown how to effectively prevent diabetes and its complications and how, in some persons with diabetes at high risk for cardiovascular disease, less intensive targets for blood glucose control may be safer. Some of the most important findings in diabetes prevention and blood glucose control are summarized here. This list does not include all studies to date but reveals those that have arguably had the greatest impact on the current management of diabetes.

What You Need to Know

Studies on the Prevention of Diabetes

Da Qing Study: Chinese researchers randomly assigned 577 men and women with prediabetes to different diabetes prevention treatments from 1986 to 1992. They found that regular exercise and a healthy diet can reduce the risk of developing type 2 diabetes. People who modified their diet over an average period of 6 years had a 31% lower risk of diabetes, while those who adopted an exercise regimen had a 46% lower risk. People who embraced both diet and exercise lifestyle changes had a 42% lower risk compared to those who continued their usual diet and exercise patterns. The benefits of these lifestyle changes for preventing diabetes persisted up to 14 years later.

The Finnish Diabetes Prevention Study: In this study, Finnish researchers randomly assigned 522 overweight middle-aged adults with prediabetes to receive intensive dietary counseling along with regular exercise or continue their usual diet and exercise patterns from 1993 to 1998. After an average of 3 years, 11% of people in the intensive lifestyle group developed diabetes compared to 23% in the usual care group, representing a 58% reduction in the risk of diabetes. The benefits of these intensive lifestyle changes for preventing diabetes persisted up to 9 years later.

Diabetes Prevention Program (DPP): In this key U.S. study from 1996 to 2001 of 3,234 overweight middle-aged adults with prediabetes, each person was randomly assigned to either an intensive lifestyle change, metformin, or placebo pills. Over an average of 3 years, the study found that those assigned to the intensive lifestyle change, which included healthier eating (based on individualized daily calorie and dietary fat goals), regular exercise (a total of 150 minutes of moder-ate physical activity every week, such as brisk walking for 30 minutes every day, 5 days a week), and a goal of 7% weight loss (for example, in a person who weighs 200 pounds, this would correspond to a 14-pound weight loss), reduced their risk of developing type 2 diabetes by 58% compared to the placebo group. In comparison, metformin treatment reduced the onset of diabetes by 31%. The lifestyle changes were particularly effective in persons 60 years and over and lessened this age group’s risk of diabetes by 71%. The benefits of reducing the development of type 2 diabetes persisted for up to 15 years for both the lifestyle and metformin groups, supporting the importance of type 2 diabetes prevention.

Studies of type 1 diabetes have found no evidence that the early use of injected or oral insulin in people at high risk for the disease can prevent or delay its onset. Research on treatments that alter the immune system (immune-modulating therapies) to delay or prevent the development of type 1 diabetes is ongoing.

Studies on the Optimal Blood Glucose Targets for People with Diabetes

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study: In this important U.S. study, 1,441 people with type 1 diabetes were randomly assigned to either an intensive or a conventional diabetes treatment from 1983 to 1993. Researchers found that damage to the retina, known as diabetic retinopathy, was dramatically reduced by maintaining an average A1C of 7% or 53 millimoles per mole (mmol/mol) in the intensively treated group compared to an average A1C of 9% or 75 mmol/mol in the conventionally treated group over an average 6.5-year period. Intensive blood glucose control also reduced the incidence of kidney disease and nerve damage, resulting in a 35% to 75% decrease in developing these types of small blood vessel (microvascular) complications during this period. However, people with tightly controlled blood glucose levels were also more likely to experience low blood glucose levels (hypoglycemia). A long-term follow-up found that participants continued to benefit after trial ended despite a slight deterioration in the glucose control of the intensively treated group and an improvement in the glucose control of the conventionally treated group. After 17 years, the group who had initially received intensive treatment had a 42% reduction in major cardiovascular events (nonfatal heart attack, stroke, or cardiovascular death) and at 30 years, modestly decreased rates of death from any cause. This all appears to be related to the 6.5 years of better glucose control during the early treatment phase of the study, suggesting that such management early in type 1 diabetes can delay or prevent cardiovascular disease.

UK Prospective Diabetes Study (UKPDS): In this hallmark study from 1977 to 1997, 5,102 people with newly diagnosed type 2 diabetes in the United Kingdom were randomly assigned to intensive therapy, leading to tighter blood glucose control (average A1C of 7% or 53 mmol/mol), compared to a group receiving conventional therapy (average A1C of 7.9% or 63 mmol/mol). Over a 10-year period, the risk of diabetes microvascular complications, including eye, kidney, and nerve disease, decreased by about 25%. A follow-up study of these patients over another 10 years after the trial ended found a lower risk of cardiovascular disease and death from any cause in the previously more intensively treated group.

Action to Control Cardiovascular Risk in Diabetes (ACCORD): Researchers in North America randomly assigned 10,251 older people (average age 62 years) with type 2 diabetes and a high risk or history of cardiovascular disease to a very intensive versus standard therapy group from 2001 to 2008. They found that trying to achieve an A1C of less than 6% (42 mmol/mol) in the intensive therapy group (compared to an A1C between 7% to 7.9% [53 to 63 mmol/mol] in the standard therapy group) increased the risk of death from any cause after just an average of 3.5 years. This was the first major trial to suggest that a very intensive treatment regimen in people with type 2 diabetes at high risk for heart disease might lead to harm. However, the overall risk of developing albuminuria (an early sign of kidney disease) was much less among those very intensively treated.

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE): Another study of 11,140 older adults with type 2 diabetes in multiple countries investigated the benefits of intensive glucose control over 5 years from 2001 to 2007. The intensive control group (average A1C of 6.5% or 48 mmol/mol) versus the standard therapy group (average A1C of 7.3% or  56  mmol/mol)  had  lower  overall  rates  of  diabetic  complications,  primarily  due to a 21% reduction in kidney disease. However, cardiovascular disease (such as  heart  attack  or  stroke)  and  death  were  not  dramatically  reduced,  even  in  a  long-term follow-up study after the trial was completed.

Veterans Affairs Diabetes Trial (VADT): This trial involving 1,791 older U.S. male military veterans with type 2 diabetes studied the effects of intensive glucose control over an average of 6 years from 2000 to 2008. The trial showed lower rates in  the  progression  of  diabetic  kidney  disease  in  the  intensive  treatment  group  (average  A1C  of  6.9%  or  52  mmol/mol)  compared  to  the  standard  treatment  group (average A1C of 8.4% or 68 mmol/mol). Though not found during the initial trial, a follow-up study demonstrated lower rates of a first cardiovascular event in the intensive treatment group but no difference in survival.

What Does It All Mean?

  • Lifestyle changes (most importantly weight loss and exercise) and certain medications (such as metformin) can delay or prevent the progression from prediabetes to type 2 diabetes.
  • Type 1 diabetes is more difficult to prevent. Some studies are exploring the use of drugs that suppress the immune system that may at least slow this condition, though side effects can develop from such treatments.
  • Tightly managing blood glucose levels (A1C of less than 7% or 53 mmol/mol) after a diagnosis of type 1 or type 2 diabetes leads to lower rates of microvascular complications (such as eye, kidney, and nerve damage) and, in long-term follow-up, cardiovascular events (such as heart disease or stroke) and likely death.
  • Vision loss and kidney damage, in particular, can be prevented by maintaining near-normal A1C levels over many years.
  • Some studies, however, suggest that very tightly managing A1C levels to less than 6% or 6.5% (42 to 48 mmol/mol) may actually do harm to certain people with type 2 diabetes and cardiovascular disease, particularly those who have had diabetes for a long time.
  • Each person with diabetes likely needs an individualized A1C goal that depends on age, medical history, and other factors.

 

Diabetes Head To ToeDr. Rita Kalyani is an Associate Professor of Medicine at Johns Hopkins University School of Medicine in the Division of Endocrinology, Diabetes & Metabolism. She is an active clinician in the Johns Hopkins Comprehensive Diabetes Center. Dr. Kalyani directs the Diabetes Management Service for Johns Hopkins’ Total Pancreatectomy Islet Auto Transplant Program. She is a new member of the DiabetesSisters Board of Directors.

This excerpt is taken from the recently published book “Diabetes Head to Toe: Everything You Need to Know about Diagnosis, Treatment, and Living with Diabetes” by Dr. Rita Kalyani, Dr. Mark Corriere, Dr. Thomas Donner, and Dr. Michael Quartuccio. Published by Johns Hopkins University Press © 2018. Reprinted by permission of the publisher.