PAN is characterized by poor peripheral circulation [12,15,23], including peripheral vascular control that can result in orthostasis. Poor peripheral circulation results in dysfunction such as poor wound healing and dry skin that facilitates wound genesis. PAN does not involve sensory and motor deficits, causing paralysis and parasthesia. In fact, if it can be felt, it is not PAN. DAN is characterized by resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, “brittle diabetes,” and hypoglycemic autonomic failure [12,15,23,24]. DAN affects many organ systems throughout the body, including the kidneys and the retina [12,15,23,24], increasing mortality risk. [2,24].
Sympathetic excess is associated with hypoglycemia . One, early hypoglycemic event (typically asymptomatic) can cause (asymptomatic) SE , leading to secondary hypertension and the start of the cascade of secondary symptoms that characterize PAN and then DAN . Establishing and maintaining normal P and S balance slows the progression of autonomic dysfunction, reducing risk of morbidity and mortality [2,3], reducing medication load, reducing hospitalizations, improving patient outcomes, and reducing healthcare costs .
Ultimately, CAN (the end stage) is demonstrated. CAN is measured as very low parasympathetic activity (with P&S Monitoring CAN is defined as RFa < 0.1 bpm2). CAN indicates risk of sudden cardiac death and may be normal for the geriatric patient with diabetes, or post-MI or post-CABG patients with diabetes. However, CAN with SE (SB > 3.0) indicates high risk of sudden cardiac death. Given that autonomic dysfunction is asymptomatic until very late in the disease, independent, simultaneous P&S Monitoring is required to diagnose and differentiate parasympathetic insufficiency (CAN) with SE (CAN with SE indicates high risk of sudden death). In fact, the American Diabetes Association recommends early and frequent P&S Monitoring [12,15,23] to stay autonomic neuropathy as long as possible. The ADA specifies that P&S Monitoring is recommended as part of the standard of care for diabetes [12,15,23] . That early detection and correction of P and S imbalance (dysfunction), and maintaining normal P and S balance reduces the risk of morbidity and mortality .
Another reason for more accurate measures of P and S activity is that DAN and CAN places a patient at increased risk of mortality under general anesthesia. Pre-operative P and S assessment is required since DAN and CAN are often asymptomatic. If undetected or unreported, the mortality risk is exacerbated. [27,28]
See “P&S Monitoring vs. HRV-alone” subsection in the “Introduction” of “Age Matched Attenuation of Both Autonomic Branches in Chronic Disease: I. Hypertension” for a short discussion of the background to independent, simultaneous P and S assessment. With independent, simultaneous measures of P and S activity, a causal relationship between diabetes and autonomic dysfunction leading to autonomic neuropathy and eventually CAN may be possible. This study considers the relationship between the resting P and S activity and duration of the chronic disease, diabetes.
Serial P&S Monitoring (ANX-3.0 Autonomic Monitor, ANSAR Medical Technologies, Inc., Philadelphia, PA) was performed on 511 consecutive patients diagnosed with type 2 diabetes mellitus (Females = 248; age = 63.4 ± 13.1, range 25 to 96) from four large ambulatory endocrinology clinics, one near Norfolk, VA, one near Baltimore, MD, one near Philadelphia, PA, and one near Albany, NY. Patients were assessed as they were, currently treated for diabetes and co-morbidities, including hypertension (56.1%) and coronary artery disease (25.2%). The data are compared with preexisting data for 234 age-matched, normal controls (ages 25-90) with no history of diabetes, hypertension, cardiovascular, autonomic, or other diagnosed disorders. The controls are from a data based that has been collected over the past decade. P&S Monitoring is based on patient responses to a standard clinical study that includes a 5-min resting baseline. Normal adult ranges for P and S are 1.0 to 10.0 bpm2. Resting P or S levels below 1.0 bpm2 indicate DAN (the diabetic term for advanced autonomic dysfunction). DAN is marked on the figure by the broken horizontal line. Resting parasympathetic levels below 0.1 bpm2 indicate CAN (see figure). CAN indicates risk of sudden cardiac death, and may be normal for geriatric patients, or post-MI and post-CABG patients. Normal SB is between 0.4 and 3.0. As Umetani, et al., indicate more resting parasympathetic activity is beneficial for geriatric patients to reduce morbidity and mortality. This translates to low-normal SB as the recommended normal for geriatric patients (0.4 < SB < 1.0). CAN with high SB indicates high risk for sudden cardiac death. Low-normal SB minimizes morbidity and morality risk . Patients with arrhythmia were excluded. Data were analyzed with SPSS 14.0.