In Type 1 Diabetes, Intensive Therapy Halves Kidney Disease
Controlling blood glucose early in the course of type 1 diabetes yields huge dividends, preserving kidney function for decades. The new finding from a study funded by the National Institutes of Health was published online in the New England Journal of Medicine to coincide with presentation at a scientific meeting.
Compared to conventional therapy, near-normal control of blood glucose beginning soon after diagnosis of type 1 diabetes and continuing an average six and a half years reduced by half the long-term risk of developing kidney disease, according to the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. The risk of kidney failure was also halved, but the difference was not statistically significant, perhaps due to the relatively small total number of patients who reached that stage of the disease.
Participants entered the DCCT on average six years after onset of diabetes when complications of diabetes were absent or very mild. Half aimed for near-normal glucose control (intensive therapy) and the others received what was then standard glucose control. After an average 22-year follow-up, 24 in the intensive group developed significantly reduced kidney function and 8 progressed to kidney failure requiring dialysis or transplantation. On conventional therapy, 46 developed kidney disease, with kidney failure in 16.
The landmark DCCT demonstrated that intensive control reduced early signs of eye, kidney and nerve damage and is the basis for current guidelines for diabetes therapy. However, the initial kidney findings were based on reductions in urine protein, a sign of kidney damage but not a measure of kidney function. Preventing a loss of kidney function and reducing kidney failure had not been proven.
Since the DCCT ended in 1993, all participants have tried to maintain excellent diabetes control and have achieved similar glucose levels. The new finding emphasizes the importance of good control of type 1 diabetes soon after diagnosis.
"Achieving near-normal glucose levels in type 1 diabetes can be challenging. But our study provides strong evidence that reinforces the benefits of reaching the goal as early as possible to slow or prevent kidney disease and other complications," said first author Ian H. de Boer, M.D., a kidney specialist at the University of Washington, Seattle. He presented the findings at the American Society of Nephrology’s annual meeting in Philadelphia.
The DCCT, conducted from 1983 to 1993 in 1,441 people with type 1 diabetes, found that intensive glucose control was superior to conventional control in delaying or preventing complications overall. EDIC continues to follow 1,375 DCCT participants to determine the long-term effects of the therapies beyond the initial treatment period. Other reports have bolstered support for intensive treatment to reduce the risk of heart disease, stroke and eye and nerve damage associated with diabetes.
"The DCCT and EDIC studies illustrate the value of long-term studies. The full benefit of treatment may not be seen for decades, especially for complications of diabetes, such as kidney disease, which can progress slowly but have devastating consequences," said Griffin P. Rodgers, M.D., director of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which oversaw the research. "Not only has NIH-sponsored research shown the benefits of early glucose control, it has provided new tools to help people with type 1 diabetes achieve that control and live longer and healthier lives."
The DCCT compared intensive to conventional control of blood glucose in people with type 1 diabetes. At the time, conventional treatment was one or two insulin injections a day with daily urine or blood glucose testing. Participants randomly assigned to intensive treatment were asked to keep glucose levels as near normal as possible. That meant trying to keep hemoglobin A1c (A1C) readings at 6 percent or less with at least three insulin injections a day or an insulin pump, guided by frequent self-monitoring of blood glucose. (A1C reflects average blood glucose over the previous two to three months.)
Nearly 26 million Americans have diabetes. In adults, type 1 diabetes accounts for 5 to 10 percent of all diagnosed cases of the disease. Formerly called juvenile-onset or insulin-dependent diabetes, type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood glucose. Type 1 diabetes usually arises in children and young adults but can occur at any age. Management involves keeping blood glucose levels as close to normal as possible with three or more insulin injections a day or treatment with an insulin pump, careful monitoring of glucose, and close attention to diet and exercise.
Type 2 diabetes, or adult-onset diabetes, accounts for about 90 to 95 percent of all diabetes diagnosed in adults. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce it. Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. African-Americans, Hispanic/Latino-Americans, American Indians, and some Asian-Americans and Native Hawaiians or other Pacific Islanders are at particularly high risk for type 2 diabetes and its complications.
Chronic kidney disease can lead to kidney failure, also called end-stage renal disease, requiring dialysis or a kidney transplant for survival. Chronic kidney disease affects more than 10 percent of Americans over age 20 and 35 percent of those over age 20 with diabetes. People with diabetes and chronic kidney disease account for 26.1 percent, or $18 billion, of Medicare costs for diabetes. Diabetes is the leading cause of kidney failure, accounting for nearly 38 percent (215,000) of Americans on dialysis or living with a kidney transplant. Each year 110,000 patients in the United States start treatment for kidney failure. These lifesaving treatments cost $42.5 billion annually.