Dataset Information

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes.

ABSTRACT:

Objective

The principal aim is to estimate the benefits of earlier versus later implementation of intensive therapy in type 1 diabetes with respect to the long-term risks of progression of a renal (microvascular) and cardiovascular (macrovascular) complication in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Research design and methods

Cox proportional hazards regression models estimated the 20-year cumulative incidence (absolute risk) and the 20-year relative risk of cardiovascular disease (CVD) and reduced estimated glomerular filtration rate (eGFR) over the first 20 years of EDIC follow-up as a function of the mean HbA_1c.

Results

A hypothetical patient treated earlier with 10 years of intensive therapy and a mean HbA_1c of 7% (53 mmol/mol) followed by 10 years with a mean of 9% (75 mmol/mol) would have a 33% reduction in the risk of CVD and a 52% reduction in reduced eGFR compared with a patient with a mean HbA_1c of 9% (75 mmol/mol) over the first 10 years followed by later intensive therapy over 10 years with an HbA_1c of 7% (53 mmol/mol). Despite both patients having the same average glycemic exposure over the 20 years, the patient with the lower HbA_1c over the first 10 years had a lower risk of progression of complications over the 20 years than the patient who had the higher value initially.

Conclusions

While implementation of intensive therapy at any time in type 1 diabetes will be beneficial, within the 20-year period modeled, earlier relative to later implementation is associated with a greater reduction in the risks of kidney and cardiovascular complications.

SUBMITTER: Lachin JM

PROVIDER: S-EPMC8929189 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes.

Lachin John M JM Bebu Ionut I Nathan David M DM

Diabetes care 20210811

<h4>Objective</h4>The principal aim is to estimate the benefits of earlier versus later implementation of intensive therapy in type 1 diabetes with respect to the long-term risks of progression of a renal (microvascular) and cardiovascular (macrovascular) complication in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.<h4>Research design and methods</h4>Cox proportional hazards regression models estimated the 20-year cumulative incidence (absolute risk) and the 20-year ...[more]

PMID: 34380706

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Project description:BackgroundTuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.MethodsWe tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival.ResultsA total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients.ConclusionsInitiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).

Project description:Aims/hypothesisIntensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes.MethodsWe performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment.ResultsBased on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] <100) and 1% had a small ARR (<0.5%, NNTB5 >200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] <100) and 29% had a small ARI (NNTH5 >200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients.Conclusions/interpretationTaking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified.Trial registrationClinicalTrials.gov NCT00145925.

Project description:BackgroundThe Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes.MethodsBetween 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies.ResultsOver a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P=0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P=0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P=0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up.ConclusionsIntensive therapy in patients with type 1 diabetes was associated with a substantial reduction in the long-term risk of ocular surgery. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360893 and NCT00360815.).

Project description:BackgroundAn impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.MethodsIn the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits.ResultsOver a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates.ConclusionsThe long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.).

Project description:BackgroundObservational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.MethodsIn this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women. The average glycated hemoglobin level was 9.2±1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.ResultsOf the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P=0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P=0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5±1.8% in the medical-therapy group, 6.4±0.9% in the gastric-bypass group (P<0.001), and 6.6±1.0% in the sleeve-gastrectomy group (P=0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (-29.4±9.0 kg and -25.1±8.5 kg, respectively) than in the medical-therapy group (-5.4±8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.ConclusionsIn obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.).

Project description:BackgroundLong-term results from randomized, controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited.MethodsWe assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 to 43 were randomly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary outcome was a glycated hemoglobin level of 6.0% or less with or without the use of diabetes medications.ResultsOf the 150 patients who underwent randomization, 1 patient died during the 5-year follow-up period; 134 of the remaining 149 patients (90%) completed 5 years of follow-up. At baseline, the mean (±SD) age of the 134 patients was 49±8 years, 66% were women, the mean glycated hemoglobin level was 9.2±1.5%, and the mean BMI was 37±3.5. At 5 years, the criterion for the primary end point was met by 2 of 38 patients (5%) who received medical therapy alone, as compared with 14 of 49 patients (29%) who underwent gastric bypass (unadjusted P=0.01, adjusted P=0.03, P=0.08 in the intention-to-treat analysis) and 11 of 47 patients (23%) who underwent sleeve gastrectomy (unadjusted P=0.03, adjusted P=0.07, P=0.17 in the intention-to-treat analysis). Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone (2.1% vs. 0.3%, P=0.003). At 5 years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (-23%, -19%, and -5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (-40%, -29%, and -8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (-35%, -34%, and -13%), and quality-of-life measures (general health score increases of 17, 16, and 0.3; scores on the RAND 36-Item Health Survey ranged from 0 to 100, with higher scores indicating better health) (P<0.05 for all comparisons). No major late surgical complications were reported except for one reoperation.ConclusionsFive-year outcome data showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycemia. (Funded by Ethicon Endo-Surgery and others; STAMPEDE ClinicalTrials.gov number, NCT00432809 .).

Project description:BackgroundIn short-term randomized trials (duration, 1 to 2 years), bariatric surgery has been associated with improvement in type 2 diabetes mellitus.MethodsWe assessed outcomes 3 years after the randomization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0% or less.ResultsThe mean (±SD) age of the patients at baseline was 48±8 years, 68% were women, the mean baseline glycated hemoglobin level was 9.3±1.5%, and the mean baseline body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.0±3.5. A total of 91% of the patients completed 36 months of follow-up. At 3 years, the criterion for the primary end point was met by 5% of the patients in the medical-therapy group, as compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering medications, including insulin, was lower in the surgical groups than in the medical-therapy group. Patients in the surgical groups had greater mean percentage reductions in weight from baseline, with reductions of 24.5±9.1% in the gastric-bypass group and 21.1±8.9% in the sleeve-gastrectomy group, as compared with a reduction of 4.2±8.3% in the medical-therapy group (P<0.001 for both comparisons). Quality-of-life measures were significantly better in the two surgical groups than in the medical-therapy group. There were no major late surgical complications.ConclusionsAmong obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. Analyses of secondary end points, including body weight, use of glucose-lowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number, NCT00432809.).

Dataset Information

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes.

Objective

Research design and methods

Results

Conclusions

Publications

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes.

Similar Datasets

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