Diabetes control and complications trial

The Diabetes Control and Complications Trial, or DCCT, was the largest, most comprehensive diabetes study ever conducted at the time.

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducted this clinical study of 1,441 volunteers with type 1 diabetes at 29 medical centers in the US and Canada between 1983 and 1993.

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

Purpose of the study
Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with diabetes. 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.

A total of 1,441 volunteers at 29 medical centers in the US and Canada were randomly assigned to receive standard therapy or intensive control therapy. All 1,441 volunteers had type 1 diabetes (then known as insulin-dependent diabetes mellitus or IDDM in the medical community and "juvenile diabetes" in the general population). People with type 2 diabetes (then known as non-insulin-dependent diabetes mellitus or NIDDM in the medical community and "sugar diabetes" or "adult-onset diabetes" in the general population) were excluded from the study, as were patients who had been diagnosed less than one year 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; some wore an external pump.

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

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

 * Clinical neuropathy was reduced 60% with intensive control treatment.
 * 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, decreased with conventional therapy

Severe hypoglycemia

 * The chief adverse event associated with intensive therapy was a 200%–300% increase in severe hypoglycemia.

Significance of the DCCT
The authors of the study featured the benefits of close control &mdash; clearly reduced eye, kidney, and nerve damage &mdash; 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 burdon 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 of tighter control in favor of the ease of the older regimens, the DCCT provides medical evidence that tighter control is measurably favorable to the patient.

To the medical insurance companies who resist the additional expense of improved insulins and improved blood glucose testing, the DCCT provides medical evidence that tighter control measurably reduces the medical costs to the insurance company in the long term.

To the governments who resist socialized or subsidized care for diabetic persons, the DCCT provides medical evidence that the costs to society for poorly treated diabetes that are avoided in the short term will only compound many times and manifest itself in the medical costs of the treatment of long term complications and in the welfare costs of blind or amputated diabetic adults.

Despite the fact that the DCCT studied only a restricted group of type 1 diabetics, many clinicians began recommending tight control to both type 1 and type 2 diabetics. Additionally, many medical centers started using a team approach to treating diabetics, consisting of a physician, nurse educator, dietitian, and behavioral therapist.

The authors of the DCCT did not however note 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. Furthermore, although they observed a far greater increase in hypoglycemia than there was reduction in eye, kidney, and nerve damage, they also failed to note that in their conclusions.