Pathophysiology
P-I-23. Diabetic neuropathy: manifestations & pathomechanism
糖尿病性神経障害の症状と病態機序
Overview
- Diabetic neuropathy = the most common diabetes-related complication
- Two types:
- Diffuse polyneuropathy (polyneuropathy)
- Focal mononeuropathy (mononeuropathy)
- Both arise from degenerative + functional damage to peripheral nerves
- Often painful, but can occur without pain → ↑risk of undetected traumatic injury → diabetic foot syndrome
Distal Symmetric Polyneuropathy (DSPN)
- Most common type, affects somatic nerves
- First: loss of sensation (“glove and stocking” distribution)
- Later: associated with pain or motor nerve involvement
Autonomic Peripheral Neuropathy
- Diffuse disorder; typical forms:
- Cardiac autonomic neuropathy (CAN)
- Cytopathy → urinary incontinence, GI dysregulation, erectile dysfunction
Pathomechanism
- Slightly different in T1DM vs T2DM; changes seen in nerve endings first → damage to nerve fibers + Schwann cells
- Possible causes:
- Insufficient blood supply
- Metabolic changes — hyperglycemia → ROS
- AGE formation (high sugar) → activates pro-inflammatory processes
Symptoms by Type
- Sensory: nerve irritability, numbness (positive); ↓sensing of pain/temperature/vibration (negative)
- Motor: muscle atrophy, flexor/extensor innervation imbalance
- Cardiovascular: tachycardia, arrhythmias, hypotension
- GI: vomiting, diarrhea, constipation, incontinence
- Urogenital: urinary retention, weak urine flow, erectile dysfunction
一問一答
▶What is the most common diabetes-related complication?
Diabetic neuropathy.
▶What are the two types of diabetic neuropathy?
Diffuse polyneuropathy and focal mononeuropathy.
▶Why is painless diabetic neuropathy dangerous?
Loss of pain sensation increases the risk of undetected traumatic injury, leading to diabetic foot syndrome.
▶What is the most common type of diabetic neuropathy, and which nerves does it affect?
Distal symmetric polyneuropathy (DSPN), which affects somatic nerves.
▶What is the characteristic sensory distribution of DSPN?
A "glove and stocking" distribution, beginning with loss of sensation.
▶What are two typical forms of autonomic peripheral neuropathy in diabetes?
Cardiac autonomic neuropathy (CAN) and cytopathy (causing urinary incontinence, GI dysregulation, erectile dysfunction).
▶Where does nerve damage in diabetic neuropathy first appear?
In the nerve endings first, then progressing to damage of nerve fibers and Schwann cells.
▶What are the main pathomechanisms of diabetic neuropathy?
Insufficient blood supply, metabolic changes (hyperglycemia → ROS), and AGE formation activating pro-inflammatory processes.
▶How does hyperglycemia contribute to nerve damage via oxidative stress?
Excess glucose metabolism generates reactive oxygen species (ROS) that damage nerve fibers and Schwann cells.
▶What are AGEs and how do they contribute to diabetic neuropathy?
Advanced glycation end-products form from high sugar levels and activate pro-inflammatory processes that damage nerves.
▶What are the positive vs negative sensory symptoms of diabetic neuropathy?
Positive: nerve irritability, numbness; negative: reduced sensing of pain, temperature, and vibration.
▶What are the motor symptoms of diabetic neuropathy?
Muscle atrophy and flexor/extensor innervation imbalance.
▶What cardiovascular symptoms occur in diabetic autonomic neuropathy?
Tachycardia, arrhythmias, and hypotension.
▶What gastrointestinal symptoms occur in diabetic autonomic neuropathy?
Vomiting, diarrhea, constipation, and incontinence.
▶What urogenital symptoms occur in diabetic autonomic neuropathy?
Urinary retention, weak urine flow, and erectile dysfunction.
▶What is the difference between polyneuropathy and mononeuropathy in diabetes?
Polyneuropathy is diffuse, symmetric damage to many nerves; mononeuropathy is focal damage to a single nerve.
▶Why does DSPN typically begin in the feet (stocking distribution)?
The longest nerve fibers are most vulnerable to metabolic and ischemic injury, so distal lower-limb sensation is lost first.
▶How does ischemia contribute to diabetic neuropathy?
Insufficient blood supply (microvascular disease) deprives nerves of oxygen and nutrients, causing degeneration.
▶Why does loss of vibration and pain sensation matter clinically?
These negative symptoms allow unnoticed foot trauma and ulceration, driving diabetic foot complications.
▶Why is cardiac autonomic neuropathy (CAN) clinically serious?
It causes resting tachycardia, arrhythmias, and orthostatic hypotension, increasing the risk of silent ischemia and sudden death.