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Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes.

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      10-year follow-up of intensive glucose control in type 2 diabetes.

      During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes. Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002). Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.) 2008 Massachusetts Medical Society
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        Effects of intensive glucose lowering in type 2 diabetes.

        Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) 2008 Massachusetts Medical Society
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          Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

           Michael Gnant (1999)
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            Author and article information

            Affiliations
            [1 ] Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT silvio.inzucchi@yale.edu.
            [2 ] International Diabetes Center at Park Nicollet, Minneapolis, MN.
            [3 ] Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC.
            [4 ] Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
            [5 ] Department of Medicine, University of Pisa School of Medicine, Pisa, Italy.
            [6 ] Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
            [7 ] Division of Endocrinology, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
            [8 ] Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
            [9 ] American Cancer Society, Atlanta, GA Department of Family and Community Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
            [10 ] Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, U.K. National Institute for Health Research (NIHR), Oxford Biomedical Research Centre, Oxford, U.K. Harris Manchester College, University of Oxford, Oxford, U.K.
            Journal
            Diabetes Care
            Diabetes care
            1935-5548
            0149-5992
            Jan 2015
            : 38
            : 1
            38/1/140 10.2337/dc14-2441 25538310

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