Diabetic autonomic neuropathy (DAN) is a group of syndromes caused by functional and/or structural impairment of the autonomic nerves, and is a common complication of diabetes. Diabetic autonomic neuropathy can involve all systems and increase the mortality rate of patients.
I. Pathogenesis
The pathogenesis of diabetic autonomic neuropathy is still unclear, and there are several theories, the most commonly used being ischemia, hypoxia and metabolic disorders. Diabetes mellitus can be associated with endoneurial microangiopathy, and parasympathetic preganglionic fibers are susceptible to hypoxic damage, which may be one of the reasons why parasympathetic nerves in diabetes mellitus are vulnerable to damage. In recent years, it is believed that the active polyol pathway and the reduced synthesis of inositol lead to autonomic nerve damage. Other theories include genetic factors and autoimmune damage.
Clinical manifestations
1.Cardiovascular system
1.1 Tachycardia: The resting heart rate of diabetic patients is about 10 times higher than normal. Diabetic autonomic neuropathy (DAN) is a group of syndromes caused by impairment of autonomic nerve function and/or structure. Diabetic autonomic neuropathy can involve all systems and increase the mortality rate of patients.
I. Pathogenesis
The pathogenesis of diabetic autonomic neuropathy is still unclear, and there are several theories, the most commonly used being ischemia, hypoxia and metabolic disorders. Diabetes mellitus can be associated with endoneurial microangiopathy, and parasympathetic preganglionic fibers are susceptible to hypoxic damage, which may be one of the reasons why diabetic parasympathetic nerves are vulnerable to damage. In recent years, it has been suggested that because polyol pathways can individually reach 130 beats/min, the heart rate slows less at night and heart rate variability decreases, which is associated with early vagal nerve damage. In later stages, when both vagus and sympathetic nerves are involved and the heart is in a completely denervated state, the heart rate does not increase significantly and tends to be fixed at about 80-95 beats/min, and does not respond to stimuli that can change the heart rate under normal circumstances.
1.2 Postural hypotension: When the patient rises from the recumbent position, the systolic blood pressure drops > 30 mmHg (1 mmHg = 0. 133 kPa) or the diastolic blood pressure drops > 20 mmHg, especially the diastolic blood pressure drops significantly, or even cannot be measured. Patients often suffer from dizziness, weakness, palpitations, sweating, visual impairment, fainting or shock, mainly due to damage to the efferent nerves in the blood pressure regulating reflex arc.
1.3 Painless myocardial infarction: Myocardial infarction in diabetic patients is often painless or associated with only mild precordial pain, which may be due to the involvement of myocardial sensory afferent nerves, weakening the sensitivity to local myocardial ischemia and interrupting pain transmission.
1.4 Sudden cardiac death: Diabetic patients occasionally suffer from severe cardiac rhythm disturbances (e.g., ventricular fibrillation, flutter) or cardiogenic shock, or even sudden death, due to various stresses.
2, digestive system Diabetic autonomic neuropathy can affect the entire digestive tract, mainly smooth muscle contraction is reduced or low muscle tone. Abnormal esophageal dynamics cause burning sensation, retrosternal discomfort, dysphagia and delayed gastric emptying, which is called “diabetic gastroparesis”. The gallbladder is enlarged and has poor contractile function, but is usually asymptomatic. Neuropathy in the small intestine is characterized by episodes of nocturnal diarrhea, which is watery and lasts from a few hours to several weeks. Neuropathy of the large intestine with constipation is a common symptom, and decreased colonic tone can lead to megacolon.
3.Genitourinary system The bladder contraction is asymptomatic in the early stage, but the residual urine may increase in the examination. In the later stage, urinary retention and sometimes filling incontinence may occur, and urinary tract infection, cystitis and pyelonephritis may be easily combined. Recent studies have shown that diabetic autonomic neuropathy plays an important role in the development of diabetic nephropathy. Damage to sympathetic and parasympathetic nerves can impair renal self-defense and cause pathological irreversible changes in the renal vasculature, which finally causes a decrease in glomerular filtration rate, impaired renal function and corresponding clinical symptoms. Autonomic neuropathy may also lead to retrograde ejaculation, penile erection, and even impotence. In women, menstrual disorders and sexual frigidity may occur.
4.Respiratory system Due to chemical, pressure receptor and intrapulmonary receptor lesions and afferent fiber denervation, the afferent impulses are reduced,
Some patients have sudden respiratory and cardiac arrest, which may be related to the autonomic neuropathy of the respiratory tract.
5.Other
In normal people, the skin temperature decreases from head to foot, but in diabetic patients, this temperature gradient is not obvious, or even the opposite. Patients with diabetes often have more sweating in the upper body,
This is related to sympathetic nerve damage. Diabetic hyperhidrosis, diabetic hypohidrosis, and localized hyperhidrosis may also be present. In a few patients, the pupils may be narrowed and the light and vergence reflexes may be weakened or absent.
Diagnosis
1.Cardiac autonomic nerve test
1.1 Parasympathetic nerve function test
The patient lies supine, breathes deeply against fixed resistance for l5 seconds, and keeps the vocal chambers open. In healthy people, tachycardia and peripheral vasoconstriction occur during expiration, and blood pressure overshoot and bradycardia occur during inspiration. In patients with autonomic neuropathy, the heart rate tends to be unchanged. In normal subjects, the R-R interval ratio of the ECG before and after movement is ≥1. 20, but in abnormal subjects, it is ≤1. 0. Or, if the patient takes 6 deep breaths/min at rest, the difference between the fastest inspiration and the slowest exhalation heart rate is ≥15 beats/m in in normal subjects, but in abnormal subjects, it is ≤10 beats/min. In normal subjects, the heart rate increases from the prone position to the standing position and then slows down. The R-R interval ratio is >1.03 in normal subjects and ≤1 in abnormal subjects.
1.2 Sympathetic function Prone blood pressure: If the systolic blood pressure drops by more than 20 mmHg when standing within 5 seconds after lying down, the autonomic neuropathy is likely to be diagnosed. The blood pressure was measured with 30% of the maximum grip force for 5 min, and the diastolic blood pressure difference was calculated before the experiment, normal ≥16mmHg, abnormal ≤10mmHg.
1.3 Radionuclide imaging allows direct observation of the innervation of the heart. The current common method to estimate sympathetic denervation of the heart by reduced myocardial uptake of norepinephrine analogs includes the application of single photon emission tomography (SPECT) or positron emission tomography (PET), both of which reveal a generalized sympathetic denervation of the heart in diabetic patients.
2. Gastrointestinal autonomic neuropathy examination
2.1 X-ray method: 3 hours after taking liquid barium meal, the abnormality is when there is still barium in the stomach.
2.2 Radioisotope method: 99mTc gliadin sulfate is used to label chicken liver,
or 99mTc phytanic acid to eggs and other food labeling, to determine the food half-emptying or full emptying time, the effect is good. Alternatively, solid foods can be labeled with 99mTc and liquids with 113I-DTPA, and both solid and liquid emptying can be observed.
2.3 Other methods include real-time ultrasound imaging, drug absorption function measurement, magnetic tracer method, resistance resistance method, gastric electrogram, intubation method, etc.
3.3 Measurement of gallbladder contraction function Patients fasted for 12 hours, fasting in the morning, lying on their back, breathing calmly, scanning the maximum long-axis section of the gallbladder with ultrasound at the right intercostal area or under the rib cage, and orally administering gallbladder contraction agent 20% mannitol 100ml, then measuring the maximum long-axis section area of the gallbladder again after 1 hour, calculating the contraction rate of the gallbladder, which is less than 30% as poor contraction.
4.Bladder function examination including bladder ultrasound, voiding map, intravenous pyelogram.
5.Sympathetic skin response (SSR): By stimulating the afferent peripheral nerves and observing the sweat gland response via the unmyelinated fibers of the efferent sympathetic nerves, diabetic autonomic neuropathy has a smaller amplitude and longer latency compared to normal subjects.
SSR provides an earlier and more sensitive response to the presence of autonomic neuropathy in diabetes than cardiac autonomic neuropathy testing. Quantitative sweating axon test (QSART) is a quantitative assessment of postganglionic sweating nerve fiber function by measuring the axon reflex-mediated sweating response using intracutaneous application of a cholinergic agonist by iontophoresis. Quantitative measurement of peripheral skin vasodilatation: Warm or cool stimulation is applied to the left arm, and skin temperature of the right hand and both feet is measured at the same time.
7. Pupil examination includes light reflex, electronic flash artificial polarized plate photography method, pupil cycle time, etc.