Problems with the ANS can range from mild to life-threatening. Sometimes, only one part of the
nervous system is affected. In other cases, the entire ANS is involved. Some conditions are
temporary and can be reversed, while others are chronic and worsen over time. Diseases such as
diabetes or Parkinson’s Disease can cause irregularities with ANS. Problems with ANS regulation
often involve organ failure or the failure of the nerves to transmit a necessary signal.

Sudomotor dysfunction testing may indicate to physicians a patient's peripheral nerve and cardiac
sympathetic dysfunction. Neuropathy is a common complication in diabetes mellitus (DM), with
60%-70% of patients affected over their lifetime. Symptoms of neuropathy are more common than
clinical neuropathy. Neuropathy may remain undetected and progress over time, leading to severe
complications. The most common associated clinical condition is peripheral neuropathy, affecting
the feet. Autonomic nerve involvement is joint but probably the most undiagnosed. Low scores in the
sudomotor may lead a medical provider to look at clinical neuropathy.

Current evidence suggests that endothelial function is an integrative marker of the net effects of
damage from traditional and emerging risk factors on the arterial wall and its intrinsic capacity for
repair. Endothelial dysfunction, detected as the presence of reduced vasodilating response to
endothelial stimuli, has been associated with major cardiovascular risk factors, such as aging,
hyperhomocysteinemia, post-menopause state, smoking, diabetes, hypercholesterolemia,
and hypertension.

Insulin resistance is defined clinically as the inability of a known quantity of exogenous or
endogenous insulin to increase glucose uptake and utilization in an individual as it does in a normal
population. Insulin resistance occurs as part of a cluster of cardiovascular, metabolic abnormalities
commonly referred to as "The Insulin Resistance Syndrome" or "The Metabolic Syndrome". This
cluster of abnormalities may lead to Type-2 diabetes, accelerated atherosclerosis, hypertension, or
polycystic ovarian syndrome depending on the genetic background of the individual
developing insulin resistance.

The specific factors that can cause this increased risk include obesity (mainly central),
hyperglycemia, hypertension, insulin resistance, and dyslipoproteinemia. When patients have
oneor more risk factors and are physically inactive or smoke, the cardiometabolic risk is
increased even more. Medical conditions that often share the above characteristics, such as
type 2 diabetes, can also increase cardiometabolic risk. The primary focus of cardiometabolic
risk treatment is managing each high-risk factor, including dyslipoproteinemia, hypertension,
and diabetes. The management of these subjects is based principally on lifestyle
measures, but various antihypertensive, lipid-lowering, insulin-sensitizing,
anti-obesity, and antiplatelet drugs could help to reduce cardiometabolic risk.

A small fiber neuropathy occurs when damage to the peripheral nerves predominantly
or entirely affects the small myelinated fibers or unmyelinated C fibers. The specific
fiber types involved in this process include both tiny somatic and autonomic fibers.
The sensory functions of these fibers include thermal perception and nociception.
These fibers are involved in many autonomic and enteric functions.

High blood glucose levels over an Additional of the year may cause a condition called autonomic
neuropathy. This is damage to the nerves that control the regulation of involuntary function. When
nerve damage affects the heart, it is called cardiac autonomic neuropathy (CAN). CAN
encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels,
resulting in abnormalities in heart rate control, vascular dynamics, and the body's ability to adjust
blood pressure. CAN is a significant cause of morbidity and mortality associated with a high risk of
cardiac arrhythmias and sudden death.

The PTG CVD risk factor is the combined total of the other seven risk factors assessments. Thus,
it considers the cardiovascular and the autonomic nervous system (ANS) measurements.