Participants were taught how to treat hypoglycemia. The DCCT took place from to The study involved 1, volunteers, ages 13 to 39, and took place in 29 medical centers in the United States and Canada. At the start of the DCCT, participants had type 1 diabetes for at least 1 year, but no longer than 15 years, and had no or only early signs of diabetic eye or kidney disease. Researchers followed participants for an average of 6. After DCCT ended, participants who used conventional treatment were taught about intensive treatment.
Participants who continued into the EDIC follow-up study were transferred to their own health care team for medical care and were encouraged to use intensive treatment. EDIC researchers are trying to understand how diabetes affects the body over time and the long-term benefits of a period of early and intensive blood glucose control in the development of later diabetes complications. DCCT participants who had tight control of their blood glucose levels had a 33 percent lower risk of death, 21 years after the DCCT ended.
Historically, people with type 1 diabetes tended to die earlier than the general population. Additionally, EDIC has shown that personalizing the frequency of eye screenings for people with type 1 diabetes based on their risk of severe eye problems and A1C level would result in. These long-term benefits occurred even though all participants had an average A1C of 8 percent during the plus years of the EDIC study. When EDIC began, participants who used conventional treatment were taught about intensive treatment, and received follow-up care from their own health care teams.
These people continue to take part in a variety of studies concerning diabetes-related health problems, including hypoglycemia, irregular heartbeats, hearing loss, weakened bones, trouble thinking clearly, physical frailty, and problems with the eyes, kidneys, nerves, feet, bladder, and sexual function.
Researchers are also looking at the small amount of insulin that some EDIC participants continue to make to determine whether it improves their health. Diabetes Control and Complications Trial DCCT DCCT Results The DCCT showed that people with type 1 diabetes who kept their blood glucose levels as close to normal as safely possible with intensive diabetes treatment as early as possible in their disease had fewer diabetes-related health problems after 6.
Author information Article notes Copyright and License information Disclaimer. Corresponding author: David M. Nathan, ude. Received Sep 7; Accepted Sep Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
This article has been cited by other articles in PMC. Introduction The plight of people with type 1 diabetes changed dramatically with the introduction of insulin therapy in 1. Research Design and Methods The eligibility criteria have been described in detail 8 , DCCT Interventions and Metabolic Goals The clinical goals for both treatment groups included absence of frequent symptoms of hyperglycemia or frequent or severe hypoglycemia, defined as requiring assistance from another person.
Outcomes Retinopathy, which was measured objectively with stereoscopic fundus photography and graded with standardized methods by a central reading center 13 , was the primary outcome used for power and sample-size calculations. Table 1 Major outcome measurements. Open in a separate window. Figure 1. Adverse Effects The two major adverse events experienced by INT subjects were hypoglycemia and weight gain 15 — Outcomes More detailed descriptions of the individual outcomes are presented in the subsequent articles in this series 21 — Figure 2.
Conclusions The DCCT and its observational EDIC follow-up were designed to determine whether the long-term complications that affect people with type 1 diabetes could be ameliorated by intensive glycemic therapy. Article Information Funding. Footnotes Clinical trial reg.
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Diabetes ; 44 — [ PubMed ] [ Google Scholar ]. Diabetes ; 57 — [ PubMed ] [ Google Scholar ]. The secondary intervention cohort could have a longer duration of diabetes 1—15 years and had to have at least one microaneurysm in either eye.
This cohort could have an AER as high as mg per 24 h. The clinical goals for both treatment groups included absence of frequent symptoms of hyperglycemia or frequent or severe hypoglycemia, defined as requiring assistance from another person.
HbA 1c was measured monthly to aid adjustment of INT and quarterly as a process outcome in both therapy groups. Only the quarterly results were used for study data. In addition, a weekly a. The subjects and DCCT clinic staff chose which modality to use. The insulins used were those that were available at the time: clear zinc regular insulin for premeal boluses and in the insulin pump and NPH, lente, and beef ultralente insulin for basal delivery in MDI regimens.
CON was consistent with standard care in the s and usually included one or two daily injections of insulin with daily urine or SMBG. The only numeric glycemic target was if HbA 1c exceeded Retinopathy, which was measured objectively with stereoscopic fundus photography and graded with standardized methods by a central reading center 13 , was the primary outcome used for power and sample-size calculations. Similarly important outcomes were nephropathy and retinopathy.
The measurements and their frequency and definitions of outcomes are included in Table 1. The frequency of interactions with the subjects and of the outcome measurements decreased substantially Table 1 ; however, the methods of measuring glycemia, other metabolic outcomes, and complications remained identical to those used during DCCT.
Several procedures were added to measure atherosclerosis Table 1. The baseline characteristics were well matched between the INT and CON for the primary prevention and secondary intervention cohorts. Although in most long-term studies loss to follow-up may compromise the integrity and interpretation of study results, the follow-up in DCCT and subsequently in EDIC has been virtually complete. At the end of DCCT, after an average of 6.
Reprinted and modified with permission from Nathan et al. Diabetes ;— The two major adverse events experienced by INT subjects were hypoglycemia and weight gain 15 — The definition established for severe hypoglycemia, which has subsequently been adopted by many studies, was meant to be relatively inclusive but not to include episodes that were recognized and treated by the patients.
To qualify as severe hypoglycemia, an episode had to require assistance from another and included coma or seizures or episodes requiring glucagon, IV dextrose, or oral carbohydrate administered by another person. Although the intent was to limit bias of ascertainment by collecting the hypoglycemia events at quarterly visits for both INT and CON subjects, INT subjects were seen and contacted more frequently than those in the CON group, and some of the differences in hypoglycemia may be attributable to differences in the frequency of ascertainment.
Despite the increased frequency of hypoglycemia, there were no adverse effects of INT or of repeated severe episodes, on rigorously and repeatedly measured cognitive function in adults or adolescents, either during the DCCT or after even longer-term follow-up 18 — The 4.
More detailed descriptions of the individual outcomes are presented in the subsequent articles in this series 21 — The magnitude and consistent direction of the effects on retinopathy, neuropathy, and nephropathy led to the termination of the study 1 year ahead of schedule by the independent oversight group.
Scnd: secondary intervention group. Reprinted with permission from Nathan et al. Considering the powerful effect that glycemic separation had on the outcomes during DCCT, the subsequent narrowing and then disappearance of the difference in HbA 1c levels between the two original therapy groups during EDIC could logically have been expected to result in the subsequent parallel development of complications.
However, the first 4 years of the EDIC follow-up demonstrated a further widening of the differences in outcomes, after adjusting for EDIC baseline outcomes Studies during EDIC suggested that glycation of long-lived proteins, such as dermal collagen, might account for this persistent effect Regardless of the mechanism, metabolic memory has lasted for at least 10 years. Major beneficial effects of INT on advanced complications 34 , including retinopathy 35 , nephropathy reduced glomerular filtration rate [GFR] 36 , and autonomic manifestations of neuropathy 37 , have been demonstrated Fig.
Finally, measurements of atherosclerosis in several macrovascular beds, including carotid intima media thickness 38 and computed tomography—measured coronary artery calcification 39 , have revealed less atherosclerosis in the INT group. The DCCT and its observational EDIC follow-up were designed to determine whether the long-term complications that affect people with type 1 diabetes could be ameliorated by intensive glycemic therapy.
Clinical trial reg.
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