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      Intensive versus conventional glycaemic control for treating diabetic foot ulcers

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          Abstract

          The estimated likelihood of lower limb amputation is 10 to 30 times higher amongst people with diabetes compared to those without diabetes. Of all non-traumatic amputations in people with diabetes, 85% are preceded by a foot ulcer. Foot ulceration associated with diabetes (diabetic foot ulcers) is caused by the interplay of several factors, most notably diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD) and changes in foot structure. These factors have been linked to chronic hyperglycaemia (high levels of glucose in the blood) and the altered metabolic state of diabetes. Control of hyperglycaemia may be important in the healing of ulcers.

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          Most cited references 60

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          Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.

          Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent. Copyright 2003 Massachusetts Medical Society
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            Impaired leucocyte functions in diabetic patients.

            This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.
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              Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005).

              Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >or=2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease. After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.
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                Author and article information

                Journal
                Cochrane Database of Systematic Reviews
                Wiley
                14651858
                January 13 2016
                Affiliations
                [1 ]College of Medicine and Dentistry, James Cook University; Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease; Townsville Queensland Australia 4814
                [2 ]Kirwan Community Health Campus; Podiatry Service; Townsville Queensland Australia
                [3 ]The Townsville Hospital; Department of Diabetes and Endocrinology; 100 Angus Smith Drive Townsville Queensland Australia 4814
                [4 ]Queensland Health; Allied Health Research Collaborative; Level 3 15 Butterfield Street Herston, Brisbane Queensland Australia 4029
                [5 ]Queensland University of Technology; School of Clinical Sciences; Brisbane Queensland Australia
                [6 ]University of Stirling; Nursing, Midwifery and Allied Health Professions Research Unit (NMAHP RU); Stirling Stirlingshire UK FK9 4LA
                [7 ]Tropical Health Solutions Pty Ltd; 72 Kokoda St Townsville Queensland Australia 4811
                [8 ]The Townsville Hospital; Department of Vascular and Endovascular Surgery; Townsville Queensland Australia 4814
                Article
                10.1002/14651858.CD010764.pub2
                26758576
                © 2016
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