Diabetes control and complications trial
Encyclopedia
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
.
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.
and neurologic
complication
s 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.
and Canada
between 1983 and 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.
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.
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.
and the effects of intensive control on quality of life
and cost effectiveness as defined by the study's authors.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
The National Institute of Diabetes and Digestive and Kidney Diseases , of the U.S. National Institutes of Health, conducts and supports research on many of the most serious diseases affecting public health...
(NIDDK). It significantly changed the management principles of Diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
from the 1990s onwards. The completed study was published in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
.
A study in the United Kingdom known as the United Kingdom Prospective Diabetes Study
United Kingdom Prospective Diabetes Study
The United Kingdom Prospective Diabetes Study was the largest clinical research study into diabetes ever conducted at the time. The study was conceived by Professor Robert Turner at Oxford University in 1976, conducted in the UK in 1977-1997, and published main results in 1998.-External links:* *...
(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 microvascularMicrovascular disease
Microangiopathy is an angiopathy affecting small blood vessels in the body. It can be contrasted to macroangiopathy....
and neurologic
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
complication
Complication (medicine)
Complication, in medicine, is an unfavorable evolution of a disease, a health condition or a medical treatment. The disease can become worse in its severity or show a higher number of signs, symptoms or new pathological changes, become widespread throughout the body or affect other organ systems. A...
s cause major morbidity and mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
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 StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
between 1983 and 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
Diabetic retinopathy
Diabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness....
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
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
injections. The intensive therapy group frequently monitored blood glucose levels and received at least three daily insulin injections; a few wore an external pump
Insulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
.
Patients in the study were followed for an average
Arithmetic mean
In mathematics and statistics, the arithmetic mean, often referred to as simply the mean or average when the context is clear, is a method to derive the central tendency of a sample space...
of 6.5 years. 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 microalbuminuriaMicroalbuminuriaMicroalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus.-Diagnosis:...
(40 mg/day) by 39%. - Intensive control therapy reduced albuminuriaAlbuminuriaAlbuminuria is a pathological condition wherein albumin is present in the urine. It is a type of proteinuria.Measurement=The amount of protein being lost in the urine can be quantified by collecting the urine for 24 hours, measuring a sample of the pooled urine, and extrapolating to the volume...
(300 mg/day) by 54%.
Neuropathy
- Intensive control therapy reduced clinical neuropathy by 60%.
- Intensive control therapy reduced abnormal nerve conductionNerve conduction studyA nerve conduction study is a test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body.Nerve conduction velocity is a common measurement made during this test...
by 44%. - Intensive control therapy reduced abnormal autonomic nervous systemAutonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
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 hypoglycemiaHypoglycemiaHypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, which is statistically significant. However, the final results published in the New England Journal of MedicineNew England Journal of MedicineThe New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
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)Intensive insulinotherapy
Intensive insulinotherapy is a therapeutic regimen for diabetes mellitus treatment. This newer approach contrasts with conventional insulinotherapy...
or continuous subcutaneous insulin infusion
Insulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
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
Conventional insulinotherapy
Conventional insulinotherapy is a therapeutic regimen for treatment of diabetes mellitus which contrasts with the newer intensive 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
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
, nurse educator, dietitian
Dietitian
Dietitians supervise the preparation and service of food, develop modified diets, participate in research, and educate individuals and groups on good nutritional habits. The goals of dietitians are to provide medical nutritional intervention, and to obtain, safely prepare, serve and advise on...
, 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 diseaseCardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
and the effects of intensive control on quality of life
Quality of life (healthcare)
Quality of Life is a phrase used to refer to an individual’s total wellbeing. This includes all emotional, social, and physical aspects of the individual’s life. However, when the phrase is used in reference to medicine and healthcare as Health Related Quality of Life, it refers to how the...
and cost effectiveness as defined by the study's authors.