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A Middle-Aged Man With Painful Dysesthesias in the Lower Limbs


Diabetic peripheral neuropathy may develop in patients who have normal or impaired fasting blood glucose or impaired glucose tolerance, precursors to frank diabetes.

A 58-year-old man presents as a new patient. He is generally well but has been concerned for about 4 months about some tingling, numbness, and mild burning in his lower legs. He denies any history of leg problems. There is no back pain, muscle weakness, bowel or bladder changes, and no symptoms in his upper extremities. He denies any visual changes, dizziness, weakness, fatigue, chest pain, shortness of breath, or abdominal discomfort. He does not smoke and drinks alcohol socially.

The patient has had hypertension for 15 years and his triglyceride level is high. His medications include lisinopril, 20 mg/d; hydrochlorothiazide, 25 mg/d; and fenofibrate, 145 mg/d.

Laboratory results from 18 months ago include normal values for CBC count and electrolytes; BUN, 16 mg/dL; creatinine, 1.6 mg/dL; fasting glucose, 102 mg/dL. Total cholesterol, 185 mg/dL; LDL-C, 110 mg/dL; triglycerides, 180 mg/dL; and HDL-C, 39 mg/dL. Results of liver function tests and urinanalysis are normal; his ECG is unremarkable.

He is 5 ft 7 in tall and weighs 192 lb. His BP is 132/75 mm Hg, pulse is 74/min, and respiratory rate is 16/min. His waist measurement is 40 in. His HEENT examination is normal. There are no bruits, lymphadenopathy, or thyromegaly. Findings from the heart, lung, and abdominal examinations are normal. His back is not tender; rectal examination shows normal tone; extremities have no rashes or edema. Neurologic examination finds decreased sensation bilaterally below the knees. Muscle strength is normal but his ankle jerks are decreased while other reflexes are equal and normal.

Are there any red flags in the history, physical examination, or labs that concern you?

Which of the following would best help you evaluate the patient? (Please choose one)

A. Electromyogram (EMG)

B. MRI study of brain and spine

C. Vitamin B12 level

D. Fasting and 2-hour postprandial glucose levels

E. Additional alcohol history from the family


You chose A. EMG. Not recommended.

Electromyography detects electrical potentials generated by muscle cells. The study may help evaluate and distinguish neuropathies from myopathies and from neuromuscular junctional disease. In this case, it seems clear that we are dealing with a neuropathy, so while this test might confirm that diagnosis, it will not help clarify the etiology and as such would not be recommended.

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You chose B. MRI of the brain and spine. Not Recommended.

When evaluating a neurologic problem it is often helpful to try to identify where the lesion is located. This man’s symptoms involve both legs below the knees and have only a sensory component. The chances of this being caused by a lesion in the brain or in the spinal cord with no other symptoms are extraordinarily rare, so imaging is not recommended.

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You chose C. Vitamin B12 level. Not the best choice.

Vitamin B12 deficiency can cause central neurologic damage and peripheral neuropathy. Classically, the deficiency is associated with a macrocytic anemia, leukopenia with hypersegmented polys, and thrombocytopenia-none of which are seen in our patient. Neurologic findings are possible in the absence of hematologic abnormalities, so this option is reasonable because the test is not costly and a B12 deficiency is easy to treat, but it is not the best choice.

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You chose D. Fasting and 2-hour postprandial glucose levels. Recommended.


The symptoms and physical findings in this patient suggest that he has a peripheral neuropathy. It is distal and non-dermatomal. There is no muscle weakness. There are many etiologies for neuropathies. In this case, it appears to be related to a host of metabolic abnormalities, including impaired fasting glucose.

At the time of presentation, the patient did not have a diagnosis of diabetes. Nevertheless, he has 5 out of 5 criteria for metabolic syndrome (Table): waist measurement, 40 in or more; elevated blood pressure, triglycerides greater than 150 mg/dL, HDL-C less than 40 mg/dL, and fasting glucose greater than 100 mg/dL.

While many health care providers might not be impressed with a fasting glucose of 102 mg/dL, that level technically is classified as impaired fasting glucose. Type 2 diabetes mellitus (T2DM) is associated with a long preclinical period of insulin resistance during which the pancreas produces excessive amounts of insulin to keep blood glucose levels normal. One often sees elevated triglyceride levels, depressed HDL-C levels, and associated hypertension. When insulin levels start to fall, glucose levels rise and the patient becomes hyperglycemic. Many investigators believe that these features of the metabolic syndrome may exist for 10 years before glucose levels become abnormal. While most patients with diabetic peripheral neuropathy have a known history of diabetes, a significant number have normal or impaired fasting blood glucose or impaired glucose tolerance.

In a patient like ours, the appropriate investigations would be a repeat fasting glucose and a 2-hour glucose challenge. Some data suggest that a HgbA1C value also may be helpful.

This patient’s fasting glucose level was 108 mg/dL, and 2-hour glucose challenge level, 227 mg/dL. The latter finding confirms the diagnosis of T2DM.

Table. Criteria for clinical diagnosis of the metabolic syndrome

Category cut points
Elevated waist circumference (US)
≥40 in (men) ≥36 in (women)
Elevated triglycerides
≥150 mg/dL
Reduced HDL cholesterol
<40 mg/dL (men) <50 mg/dL (women)

Systolic ≥130 mm Hg and/or
Diastolic ≥85 mm Hg

Elevated fasting plasma glucose
≥100 mg/dL

a Treatment for the condition serves as alternate indicator.
Source: Alberti KG et al. Circulation. 2009;120:1640-1645.

Teaching points:

• The metabolic syndrome often is a pre-diabetic state and puts the patient at marked risk for overt diabetes.

• Diabetic peripheral neuropathy can occur in patients who have normal or impaired fasting blood glucose or impaired glucose tolerance.

• The presence of peripheral neuropathy in a patient with metabolic syndrome should lead to a workup for undiagnosed diabetes.


• Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640-1645.

• Holland NR, Prodon CI. Peripheral neuropathy and “borderline” diabetes. J Am Board Fam Med. 2004;17:127-130.

• Ziegler D, Rathmann W, Dickhaus T, et al. KORA Study Group. Prevalence of polyneuropathy in pre-diabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care. 2008;31:464-469.

• Gregg EW, Gu Q, Williams D, et al. Prevalence of lower extremity diseases associated with normal glucose levels, impaired fasting glucose, and diabetes among U.S. adults aged 40 or older. Diabetes Res Clin Pract. 2007;77:485-488.

« Click to see other choices.« Click to see other “Primary Care Challenges”

You chose E. Obtain alcohol history from the family. Not the best choice right now.

Excessive alcohol intake can also cause a peripheral neuropathy. Our patient claims to be a “social drinker,” but patients may not disclose, especially on a first visit, how much they really drink. The elevated blood pressure and triglycerides could be associated with excessive alcohol use. His liver function tests are normal, however, and he has no physical signs of chronic alcoholism (red palms, spider angiomata, hepatomegaly, splenomegaly, gynecomastia). In people who are alcoholic, the CBC count may show macrocytosis, which is not true of this patient. While more history is always a good option, in this case, it it is not the best choice for a next step.

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