Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial (DCCT), was a landmark medical study conducted by the United States National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). It significantly changed the management principles of Diabetes mellitus from the 1990s onwards. The completed study was published in the New England Journal of Medicine in 1993.

A study in the United Kingdom known as the United Kingdom Prospective Diabetes Study (UKPDS), released in 1999, found similar results for people with type 2 diabetes. Between the two studies, the treatment of people with diabetes was significantly changed.

Purpose

Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with diabetes, and is the leading cause of blindness in the developed world. This study examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of those complications.

Methods

A total of 1,441 volunteers with type 1 diabetes were recruited from 29 medical centers in the United States and Canada between 1983 and 1989, and were followed up until 1993. Each were randomly assigned to receive standard therapy or intensive control therapy. Patients with type 2 diabetes were excluded from the study, as were those who had been diagnosed less than one year ago or more than 15 years before.

Of those studied, 726 had no retinopathy at the beginning of the trial, and 715 had limited retinopathy. Those with greater degrees of retinopathy were excluded from the trial.

The volunteers were randomly assigned to one of two groups. The conventional diabetes therapy group received one or two daily insulin injections. The intensive therapy group frequently monitored blood glucose levels and received at least three daily insulin injections; a few wore an external pump.

Patients in the study were followed for an average of 6.5 years. The appearance and progression of retinopathy and certain other complications were regularly assessed.

Results

Retinopathy

• Among those volunteers who previously had exhibited no retinopathy, intensive control therapy reduced the adjusted mean risk by 76%.
• Among those who had mild retinopathy, intensive control therapy slowed the progression of retinopathy by 54% and reduced the development of severe nonproliferative retinopathy by 47%.

Albuminuria

• Intensive control therapy reduced microalbuminuria (40 mg/day) by 39%.
• Intensive control therapy reduced albuminuria (300 mg/day) by 54%.

Neuropathy

• Intensive control therapy reduced clinical neuropathy by 60%.
• Intensive control therapy reduced abnormal nerve conduction by 44%.
• Intensive control therapy reduced abnormal autonomic nervous system function by 53%.
• Nerve conduction velocities remained stable with intensive control therapy, but decreased with conventional therapy.

Severe hypoglycemia

• The chief adverse event associated with intensive therapy was a 200%–300% increase in severe hypoglycemia, which is statistically significant. However, the final results published in the New England Journal of Medicine do not disclose that the study began in 1983 with only 278 participants, and the first two years were devoted to planning and feasibility studies. The DCCT's full cohort of 1,441 participants was not achieved until 1989, only four years before the study ended. Of the original 278 participants, 8 (2.9%) dropped out and 11 (3.9%) died, mostly due to severe hypoglycemia. Changes were subsequently made in the eligibility criteria for the full-scale trial to exclude anyone with this very common short-term complication of diabetes treatment, which also raises questions about exactly how "random" the selection process really was.

Implications

The authors of the study featured the benefits of close control — clearly reduced eye, kidney, and nerve damage — in their conclusion. This supports the clinical value of tighter control afforded by multiple daily injections (MDI) or continuous subcutaneous insulin infusion combined with lower blood glucose targets and lower HbA1C goals. Prior to the DCCT, there simply was no medical proof that the additional burden of intensive insulin therapy over the convenience of fewer shot per day with conventional insulinotherapy was worth the tradeoff.

In hindsight, this conclusion now seems obvious. However, to the diabetic adult patient who resists the additional burden and/or expense of tighter control, the DCCT provides medical evidence that tighter control is measurably favorable to the patient.

The DCCT provided quantifiable justification to healthcare providers that the additional expenses associated with intensive glycemic control and close monitoring of diabetes are cost effective. The medical costs of managing the complications of poorly-treated diabetes and the welfare costs of blind or amputated diabetic adults, or who die or are incapacitated whilst still of a working (economically active) age are significantly greater than any savings that might be made by withholding primary care.

Despite the fact that the DCCT studied only a restricted group of people with type 1 diabetes, many clinicians began recommending tight control to both people with type 1 and type 2 diabetes. Additionally, many medical centers started using a team approach to treating diabetics, consisting of a physician, nurse educator, dietitian, and behavioral therapist, although the practice remains limited because of the manner in which healthcare is actually delivered and paid for in many places.

Limitations

The authors of the DCCT noted that they were unable to show any reduction in cardiovascular morbidity and mortality. This is important because people with diabetes are two to four times more likely to have heart disease than persons without diabetes, and 75% of all diabetes-related deaths are from cardiovascular disease. A possible explanation for this is that the population studied in the DCCT was relatively young (the age range of participants was 13–39 years), and therefore their likelihood of having a significant cardiovascular event during the follow-up period was low. Furthermore, although they observed a far greater increase in hypoglycemia than there was reduction in eye, kidney, and nerve damage, they failed to note this in the conclusions.

To succeed with intensive therapy, a person with diabetes must take three or more daily injections of insulin (or insulin pump therapy), four or more daily blood glucose tests, and follow dietary and insulin dosing instructions. The principle underlying the belief that more diabetes education will improve a person's ability and/or desire to practice intensive insulin therapy is grounded in the assumption that it is reasonable to expect a person to perform these acts every day for the rest of his or her life.

When all is said and done, the fact remains that the rate and incidence of blindness, amputation, heart attacks, and kidney failure caused by diabetes—as reported by the NIH—continue to rise, suggesting that there are limits to the expectation that current treatment modalities are capable of delivering on the full promise. Insurance companies and health care providers ponder this failure and, with few exceptions, conclude that "educating diabetics" to adhere to an intensive regimen of injections and diets will somehow miraculously solve the problem. But some make a fairly compelling argument that the treatment itself is unreasonable and, that until issues related to hypoglycemia and human behavior are resolved, intensive therapy will remain a lofty theory that fails abysmally in practice.

Epidemiology of Diabetes Interventions and Complications

Epidemiology of Diabetes Interventions and Complications (EDIC) was a follow-up study on 90% of the participants that looked into cardiovascular disease and the effects of intensive control on quality of life and cost effectiveness as defined by the study's authors.