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      Historical HbA 1c Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88

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          Abstract

          OBJECTIVE

          Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycemic legacy effects have not been explained. We examined their relationships with prior individual HbA 1c values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy.

          RESEARCH DESIGN AND METHODS

          Twenty-year ACM and MI hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. Impact of HbA 1c values over time was analyzed by weighting them according to their influence on downstream ACM and MI risks.

          RESULTS

          Hazard ratios for a one percentage unit higher HbA 1c for ACM were 1.08 (95% CI 1.07–1.09), 1.18 (1.15–1.21), and 1.36 (1.30–1.42) at 5, 10, and 20 years, respectively, and for MI was 1.13 (1.11–1.15) at 5 years, increasing to 1.31 (1.25–1.36) at 20 years. Imposing a one percentage unit lower HbA 1c from diagnosis generated an 18.8% (95% CI 21.1–16.0) ACM risk reduction 10–15 years later, whereas delaying this reduction until 10 years after diagnosis showed a sevenfold lower 2.7% (3.1–2.3) risk reduction. Corresponding MI risk reductions were 19.7% (22.4–16.5) when lowering HbA 1c at diagnosis, and threefold lower 6.5% (7.4–5.3%) when imposed 10 years later.

          CONCLUSIONS

          The glycemic legacy effects seen in type 2 diabetes are explained largely by historical HbA 1c values having a greater impact than recent values on clinical outcomes. Early detection of diabetes and intensive glucose control from the time of diagnosis is essential to maximize reduction of the long-term risk of glycemic complications.

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          Most cited references34

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus

            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. 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. 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. Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
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              Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

              The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                October 2021
                08 July 2021
                08 July 2021
                : 44
                : 10
                : 2231-2237
                Affiliations
                [1] 1Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
                [2] 2Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
                [3] 3Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden
                [4] 4Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, U.K.
                Author notes
                Corresponding author: Marcus Lind, marcus.lind@ 123456gu.se
                Author information
                https://orcid.org/0000-0002-3796-9283
                https://orcid.org/0000-0002-1256-874X
                Article
                202439
                10.2337/dc20-2439
                8740943
                34244332
                c2db2ec8-482f-416e-af75-db87f501fe22
                © 2021 by the American Diabetes Association

                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. More information is available at https://www.diabetesjournals.org/content/license.

                History
                : 02 October 2020
                : 03 May 2021
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 36, Pages: 7
                Categories
                1043
                Long-term Effects of Earlier Glycemic Control

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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