The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

Published on Sep 30, 1993in The New England Journal of Medicine74.699
· DOI :10.1056/NEJM199309303291401
Diabetes Control13
Estimated H-index: 13
H. Duffy1
Estimated H-index: 1
+ 16 AuthorsJ. Gonzalez1
Estimated H-index: 1
Background Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. Methods A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. Results In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Conclusions Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
📖 Papers frequently viewed together
8,220 Citations
9,179 Citations
1 Author (Michael Brownlee)
9,031 Citations
Background A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established. Methods We randomly assigned 102 patients with insulin-dependent diabetes mellitus, nonproliferative retinopathy, normal serum creatinine concentrations, and unsatisfactory blood glucose control to intensified insulin treatment (48 patients) or standard insulin treatment (54 patients). We then evaluated them for...
1,045 CitationsSource
#1Carolyn Siebert (NIH: National Institutes of Health)H-Index: 8
#2Charles M. Clark (NIH: National Institutes of Health)H-Index: 1
Abstract Many clinical trials incorporate a system for monitoring emerging data that utilizes a committee composed of individuals who are independent of the investigators conducting the study. Although this is a common practice, there is a paucity of publications examining the operating methods of these groups. This paper describes the composition, functions, and procedures of the Data, Safety and Quality Review Group (DSQ) of the Diabetes Control and Complications Trial (DCCT). The DSQ is not m...
10 CitationsSource
#1L.J. Wei (UM: University of Michigan)H-Index: 2
#2John M. Lachin (GW: George Washington University)H-Index: 99
In this article we review the important statistical properties of the urn randomization (design) for assigning patients to treatment groups in a clinical trial. The urn design is the most widely studied member of the family of adaptive biased-coin designs. Such designs are a compromise between designs that yield perfect balance in treatment assignments and complete randomization which eliminates experimental bias. The urn design forces a small-sized trial to be balanced but approaches complete r...
187 CitationsSource
#1Mary Schumer (University of Louisville)H-Index: 2
#2Gary Burton (University of Louisville)H-Index: 1
Last. Michael Pfeifer (University of Louisville)H-Index: 60
view all 5 authors...
Abstract To determine the feasibility of utilizing a central, computerized unit to analyze autonomic nervous system function tests for a 10-year, multicenter, clinical trial, the Autonomic Nervous System Reading Center was established. The Reading Center selected and standardized testing methods, designed the testing protocol, developed testing equipment, computerized data analysis, and instituted measures to monitor data quality. Three cardiovascular testing methods, RR-variation, Valsalva mane...
24 CitationsSource
Last. Leiv SandvikH-Index: 3
view all 4 authors...
• Forty-five diabetic patients were randomized and treated with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (MI), or conventional insulin treatment (CIT) for 41 months. Near-normoglycemia was obtained with CSII and MI but not with CIT. A transient increase in microaneurysms and hemorrhages was seen at three months in CSII-treated patients. After 41 months, a moderate progression in microaneurysms and hemorrhages was registered, as assessed from fundus photographs...
76 CitationsSource
#1Bo Feldt-Rasmussen (Memorial Hospital of South Bend)H-Index: 29
#2ElisabethR. Mathiesen (Memorial Hospital of South Bend)H-Index: 1
Last. Torsten Deckert (Memorial Hospital of South Bend)H-Index: 54
view all 3 authors...
Abstract 36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years. The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventio...
401 CitationsSource
Last. Aagenaes OH-Index: 2
view all 5 authors...
In a study of retinopathy during one year of tight blood glucose control 45 type I (insulin dependent) diabetics without proliferative retinopathy were randomised to receive either continuous subcutaneous insulin infusion, multiple insulin injections, or conventional insulin treatment (controls). Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment. Blind evaluation of fluorescein angiograms performed three monthly showed progressi...
275 CitationsSource
#1Ronald KleinH-Index: 215
Last. David L. DeMetsH-Index: 84
view all 5 authors...
• In a population-based study in southern Wisconsin, 1,370 patients given diagnoses of diabetes at age 30 years or older were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 28.8% in persons who had diabetes for less than five years to 77.8% in persons who had diabetes for 15 or more years. The rate of proliferative diabetic retinopathy varied from 2.0% in persons ...
1,129 CitationsSource
#1Ronald KleinH-Index: 215
Last. David L. DeMetsH-Index: 84
view all 5 authors...
• In a population-based study in southern Wisconsin, 996 insulin-taking, younger-onset diabetic persons were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 17% to 97.5% in persons with diabetes for less than five years and 15 or more years, respectively. Proliferative retinopathy varied from 1.2% to 67% in persons with diabetes for less than ten years and 35 or mo...
1,479 CitationsSource
#1Torsten Lauritzen (Gentofte Hospital)H-Index: 63
#1T. Lauritzen (Gentofte Hospital)H-Index: 14
Last. Torsten Deckert (Gentofte Hospital)H-Index: 54
view all 4 authors...
Abstract 30 insulin-dependent diabetic patients with background retinopathy were randomised to conventional treatment (UCT) or treatment with continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 1 year with fortnightly seven-sample home blood glucose measurements and retinal examinations every 6 months. Mean blood glucose and stable haemoglobin A 1c during months 3-12 were significantly lower in the CSII than the UCT group. Retinal morphology deteriorated during ...
301 CitationsSource
Cited By15160
#1Alan M. JacobsonH-Index: 57
#2Christopher M. Ryan (University of Pittsburgh)H-Index: 68
Last. DcctH-Index: 8
view all 13 authors...
BACKGROUND With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age. METHODS 1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Co...
1 CitationsSource
Abstract null null Aims null To investigate the prevalence of diabetes-related chronic complications (DRCCs) and its associated factors in Brazilian adolescents with type 1 diabetes (T1D). null null null Methods null This nationwide study was conducted in 14 public clinics in 10 cities, with 1,760 patients, 367 adolescents, with 328 eligible for this study. Evaluated DRCCs were retinopathy (DR), chronic kidney disease (CKD), peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CA...
#1Liguo Yang (Zhengzhou University)
#2Guangxing Yang (Zhengzhou University)
Last. Xialian Li (Zhengzhou University)
view all 0 authors...
BACKGROUND The hallmark of type 1 diabetes (T1D) is an absolute lack of insulin. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients. METHODS This retrospective study was conducted among 1943 patients with clinically diagnosed T1D. Medical records on patients' demographics, anthropometric measurements, and clinical manifestation were collected. Acco...
#1Peter H Scanlon (University of Gloucestershire)H-Index: 24
#2Clareece R Nevill (Cheltenham General Hospital)
Last. Victor Chong (Boehringer Ingelheim)H-Index: 4
view all 0 authors...
PURPOSE To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR). METHODS Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log-linear r...
Last. Duffee D
view all 0 authors...
BackgroundThe classic association of glycemic control as represented by glycosylated hemoglobin (Glyco% or HbA1c) with progression of micro and macro vascular clinical complications is well documented. However, use of the advanced glycation end product (AGE) axis as a marker for early diastolic hemodynamic changes leading to clinical heart failure has been suggested but is less well characterized. This study explored the association between elevated Glyco% and Fibrosis 4 (FIB-4, a 4-component ma...
#1J. Jaime Miranda (UPCH: Cayetano Heredia University)H-Index: 56
#2M. Amalia Pesantes (UPCH: Cayetano Heredia University)H-Index: 5
Last. Robert W Aldridge (UCL: University College London)H-Index: 31
view all 0 authors...
Background : Financial incentives may improve the initiation and engagement of behaviour change that reduce the negative outcomes associated with non-communicable diseases. There is still a paucity in guidelines or recommendations that help define key aspects of incentive-oriented interventions, including the type of incentive (e.g. cash rewards, vouchers), the frequency and magnitude of the incentive, and its mode of delivery. We aimed to systematically review the literature on financial incent...
#1Pun Yuet Lam (Li Ka Shing Faculty of Medicine, University of Hong Kong)H-Index: 2
#2Shing Chuen Chow (Li Ka Shing Faculty of Medicine, University of Hong Kong)
Last. Nicholas Siu Kay Fung (Li Ka Shing Faculty of Medicine, University of Hong Kong)
view all 0 authors...
Background and objective null Diabetic retinopathy, a microvascular complication of diabetes mellitus, is one of the most important causes of visual loss in developed countries. Our objective is to evaluate the efficacy of intensive versus conventional glycemic control of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients in terms of ophthalmologic outcome, pathogenesis of the early worsening of diabetic retinopathy, risk factors for early worsening and diabetic retinop...
Type 2 diabetes has been a global health challenge over the decades and is among the leading causes of death. Several treatment approaches have been developed, but more effective and new therapies are still needed. The role of adenosine in glucose and lipid homeostasis has offered a different therapeutic approach. Adenosine mediates its physiological role through the activation of adenosine receptors. These adenosine receptors have been implicated in glucose and lipid homeostasis. The ability of...
Telemonitoring in type 2 diabetes (T2D) is mainly based on glucose monitoring. A new type of connected device which routinely gathers data on weight, physical activity and food intake could improve patients’ diabetes control. The main aim of this study was to assess the efficacy of an at-home interventional programme incorporating such devices and lifestyle education software on diabetes control, i.e., change in HbA1c, compared to standard care. This multicentre study randomly assigned 282 peopl...
#1Amber M. Healy (Heritage College of Osteopathic Medicine)H-Index: 3
#2Jarrod L. Uhrig (VT: Virginia Tech)
Last. Archana R. Sadhu (Cornell University)H-Index: 8
view all 0 authors...
CONTEXT Primary care physicians need a strong foundation in diabetes management, as they are the first line of care for patients with this complex disease, which is increasing in frequency in the United States. This foundational training begins in medical school, but its applications become more important during residency. OBJECTIVES To quantify osteopathic and allopathic family medicine residents' amount of exposure to diabetes in residency training, investigate referral patterns related to dia...