What is the first neurological sign seen in a patient with a likely diagnosis of hyperglycemia (elevated blood glucose) due to diabetes mellitus?

First Neurological Sign in Diabetic Peripheral Neuropathy

Decreased vibration sensation over the toes is the first neurological sign typically seen in a patient with hyperglycemia due to diabetes mellitus. 1, 2

Pathophysiology and Progression of Diabetic Neuropathy

Diabetic peripheral neuropathy (DPN) is a length-dependent process that begins distally and progresses proximally. The pathophysiology involves:

• Hyperglycemia-induced damage to small nerve fibers (70-90% of peripheral nerves) 1
• Metabolic abnormalities affecting Schwann cells 3
• Progressive axonal damage leading to sensory loss 4

Assessment of Diabetic Peripheral Neuropathy

According to the American Diabetes Association's 2024 Standards of Care, assessment for distal symmetric polyneuropathy should include:

1. Careful history
2. Assessment of small-fiber function (temperature or pinprick sensation)
3. Assessment of large-fiber function (vibration sensation using a 128-Hz tuning fork)
4. Annual 10-g monofilament testing 1

Sequence of Neurological Signs in Diabetic Neuropathy

The progression of neurological signs in diabetic neuropathy typically follows this pattern:

1. Decreased vibration sensation over the toes (earliest sign) 1, 2
2. Loss of pinprick and temperature sensation (small fiber damage)
3. Loss of proprioception
4. Loss of deep tendon reflexes (particularly ankle reflexes)
5. Motor weakness (occurs later in disease progression)

Clinical Implications

• Vibration sensation testing using a 128-Hz tuning fork at the great toe is a sensitive screening tool for early detection of diabetic neuropathy 5
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic, making objective testing crucial 1
• Early detection allows for interventions to prevent progression, including:
  • Optimizing glycemic control
  • Foot care education
  • Appropriate footwear

Common Pitfalls in Assessment

• Relying solely on patient-reported symptoms (many patients with early neuropathy are asymptomatic)
• Waiting for pain symptoms to develop before screening (pain occurs later or may never develop)
• Focusing on motor symptoms (weakness of the foot is a late manifestation)
• Overlooking vibration testing in routine examinations

Key Points for Clinical Practice

• Screen all patients with type 2 diabetes for DPN at diagnosis and annually thereafter 1
• For type 1 diabetes, begin screening 5 years after diagnosis 1
• Decreased vibration sensation is often present before patients develop symptoms
• HbA1c levels and duration of diabetes are significantly associated with development of neuropathy 6
• Early detection and glycemic control can prevent progression of neuropathy

In this patient with a random blood glucose of 322 mg/dL, decreased vibration sensation over the toes would be the earliest neurological sign of diabetic neuropathy, preceding pain, weakness, or loss of deep tendon reflexes.