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      Continuous, non-invasive measurement of the haemodynamic response to submaximal exercise in patients with diabetes mellitus: evidence of impaired cardiac reserve and peripheral vascular response

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      Heart
      BMJ Group

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          Abstract

          Background:

          Reduced exercise capacity in diabetics has been attributed to limitations in cardiac function and microvascular dysfunction leading to impaired oxygen supply and nutritive perfusion to exercising muscles.

          Objective:

          To study changes in cardiac function and microvascular utilisation during exercise in diabetic individuals compared to age-matched controls.

          Methods:

          Diabetics with glycosylated haemoglobin (HbA 1c) <8 (n = 31), diabetics with HbA 1c ⩾8 (n = 38) and age-matched non-diabetic controls (n = 32) performed exercise at 50 W for 10 minutes followed by recovery, with continuous monitoring of cardiac function by impedance cardiography and regional flow and oxygen saturation by laser Doppler and white light spectroscopy.

          Results:

          In the diabetics, cardiac reserve during exercise and cardiac overshoot during recovery are significantly reduced because of reduction in capacity to increase stroke volume. Regional flow to the exercising muscle is reduced and there is also disproportionately greater desaturation of the regional flow. Abnormalities in cardiac function and regional perfusion are related to the severity of diabetes.

          Conclusion:

          Cardiac response to exercise is attenuated significantly in diabetic individuals. Simultaneously, there is impairment in the regional distribution. These changes could be the harbinger of reduced exercise capacity in diabetics.

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          Most cited references25

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          Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I.

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            Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications.

            The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.
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              Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes.

              It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism. We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac high-energy phosphate metabolites were measured at rest using 31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50+/-0.11, than the healthy volunteers, at 2.30+/-0.12. The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free fatty acid concentrations. Although skeletal muscle energetics and pH were normal at rest, PCr loss and pH decrease were significantly faster during exercise in the patients with diabetes, who had lower exercise tolerance. After exercise, PCr recovery was slower in the patients with diabetes and correlated with tissue reoxygenation times. The exercise times correlated negatively with the deoxygenation rates and the hemoglobin (Hb)A1c levels and the reoxygenation times correlated positively with the HbA1c levels. Type 2 diabetic patients with apparently normal cardiac function have impaired myocardial and skeletal muscle energy metabolism related to changes in circulating metabolic substrates.
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                Author and article information

                Journal
                Heart
                heart
                heartjnl
                Heart
                BMJ Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1355-6037
                1468-201X
                2010
                22 October 2009
                1 January 2010
                22 October 2009
                : 96
                : 1
                : 36-41
                Affiliations
                [1 ]Torrent Research Centre, Village Bhat, Gandhinagar, Gujarat, India
                [2 ]Veeda Clinical Research, Old Convent of Notre Dame, Derriford, Plymouth, UK
                [3 ]Veeda Clinical Research, Ambawadi Ahmedabad, Gujarat, India
                Author notes
                [Correspondence to ] Dr Chaitanya Dutt, Torrent Research Center, PO Bhat, District of Gandhinagar 382428, Gujarat, India; cdutt@ 123456torrentpharma.com
                Article
                ht177113
                10.1136/hrt.2009.177113
                3272706
                19850585
                49523413-4cad-410d-a2d2-729bae24df45
                © Joshi et al 2010

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2009
                Categories
                Original Articles
                1506
                Diabetes, lipids and metabolism

                Cardiovascular Medicine
                Cardiovascular Medicine

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