MD Conference Express - ENDO 2015 - (Page 23)

SElECTED UPDATES Mechanisms Underlying Cardiovascular Disease in Diabetes Mellitus Written by Emma Hitt Nichols, PhD Over the last 20 years, the prevalence of diabetes mellitus (DM) in the United States has nearly doubled to 9.3% [Selvin E et al. Ann Intern Med. 2014], with rising prevalence observed in children and adolescents [Dabelea D et al. JAMA. 2014]. Rodica Pop-Busui, MD, PhD, University of Michigan, Ann Arbor, Michigan, USA, discussed the role of diabetic neuropathy on cardiovascular (CV) risk in patients with DM. Neuropathies affect up to 50% of patients with DM [Pop-Busui R et al. Diabetes Care. 2013]. The diagnosis of peripheral diabetic neuropathy can be aided by using a simple clinical tool, the Michigan Neuropathy Screening Instrument [Herman WH et al. Diabet Med. 2012; Feldman et al. Diabetes Care. 1994]. In addition, the type of symptoms that a patient experiences can be indicative of the type of nerve fibers that are affected (Table 1). Importantly, the heart is innervated by both sympathetic and parasympathetic nerves. Diabetic neuropathy is associated with high morbidity and low quality of life and is an independent predictor of mortality in patients with type 1 DM (T1DM) and type 2 DM (T2DM). For instance, the EURODIAB IDDM Prospective Complications Study [SoedamahMuthu SS et al. Diabetes Care. 2008] reported that both CV autonomic and peripheral neuropathy were associated with similar CV disease (CVD) mortality risk after 7 years of follow-up. An analysis of > 8000 patients with T2DM enrolled in the ACCORD trial [Pop-Busui R et al. Diabetes Care. 2010] who had valid cardiac autonomic neuropathy (CAN) data found that presence of CAN at baseline was associated with higher all-cause and CVD mortality risk after 3.5 years of follow-up. Similarly, a post hoc analysis of the ACCORD trial found that all-cause mortality was significantly associated with self-reported history of neuropathy (PInteraction = .0008) [Calles-Escadrón J et al. Diabetes Care. 2010]. Furthermore, the ADMIRE-HF trial [Jacobson AF et al. J Am Coll Cardiol. 2010] demonstrated that both cardiac death (r = -0.83; P < .01) and all-cause mortality (r = -0.89; P < .001) were highly correlated with lower iodine-123 metaiodobenzylguanidine retention at baseline, an imaging technique to assess integrity of cardiac sympathetic innervation and CAN (Figure 1). Emerging data suggest a link among CAN, left ventricle remodeling, and myocardial dysfunction as reported by several studies. The DCCT/EDIC study [Pop-Busui R et al. J Am Coll Cardiol. 2013] found that patients with DM and CAN had significantly greater cardiac output (P < .0001), left ventricular mass (P < .0001), and mass-tovolume ratio (P < .0001), compared with patients who did not have CAN. Abd A. Tahrani, MD, PhD, University of Birmingham, Birmingham, United Kingdom, discussed the possible link between obstructive sleep apnea (OSA) and CVD. OSA has been linked to many factors that are involved in the pathogenesis of CVD risk in population studies, such as hypertension [Peppard PE et al. N Engl J Med. 2000], insulin resistance [Tahrani AA et al. Curr Opin Pulm Med. 2013], inflammation [Lavie L. Front Biosci (Elite Ed). 2012], and obesity. Continuous positive airway pressure (CPAP) has been shown to lower blood pressure (BP) and improve insulin resistance in randomized controlled trials [Hu X et al. J Clin Hypertens (Greenwich). 2015; Iftikhar IH et al. J Clin Sleep Med. 2013]. Limited data also suggest that CPAP can improve insulin resistance and BP in patients with T2DM [Chen L et al. Arch Med Sci. 2014; Myhill PC et al. J Clin Endocrinol Metab. 2012]. OSA has been more directly linked to CVD. In one study, the cumulative incidence of fatal and nonfatal CV events over an average follow-up of 10.1 years was higher in patients with untreated severe OSA compared with CPAP-treated patients, patients with mild OSA, simple snorers, and the control group [Marin JM et al. Lancet. 2005]. In patients with T2DM, OSA was significantly associated with stroke (OR, 2.57; 95% CI, 1.03 to 6.42; P = .04) in a cross-sectional analysis of a subgroup of the Look AHEAD trial [Rice TB et al. Sleep. 2012]. Table 1. Symptoms Indicating Nerve Fiber-Type Involvement Type of Nerve Fibers Symptoms Large myelinated fibers Numbness, tingling, poor balance; clinical exam that demonstrates abnormal reflexes or proprioception Small myelinated and unmyelinated fibers Pain, burning, electric shocks, stabbing pain; thermal or pinprick sensation; tachycardia Official Peer-Reviewed Highlights From ENDO 2015 23

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MD Conference Express - ENDO 2015