A cross-sectional study examined the relationships among neurophysiological tests in patients with diabetes. The study included 130 individuals: 25 healthy controls and 105 with diabetes, classified by the presence or absence of neuropathy. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation, along with neurological exams and symptom scores. Correlation and cluster analysis were used to determine relationships between neurophysiological tests. Results showed that neurophysiological tests were abnormal in patients with diabetic neuropathy compared to healthy controls and those without neuropathy. Correlations among tests varied widely, with some tests showing little to no correlation. A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical nerve fiber subtypes. The study concluded that different neurophysiological tests measure distinct parameters and are not interchangeable. However, only a small number of tests are needed to clinically differentiate individuals with neuropathy from those without. The natural clustering of patients and healthy controls suggests that population variations should be considered in future studies of diabetic neuropathy. The study found that nerve conduction studies, assessing large myelinated fibers, are widely used in clinical practice. Damage to small, unmyelinated nerves or autonomic fibers can be measured by quantitative sensory testing, autonomic testing, and laser Doppler flowmetry. The study also found that tests of large fiber function had higher sensitivity and specificity than small fiber or autonomic tests. The results showed that all tests of nerve conduction studies, 4 of 6 autonomic tests, and 9 of 11 quantitative sensation tests differentiated diabetic subjects with neuropathy from those without. Tests of cutaneous blood flow did not reliably differentiate diabetic subjects with neuropathy from those without. The tests with the highest sensitivity and specificity were the blood pressure fall during phase 2 of the Valsalva maneuver and the cold-pain detection threshold in the foot. The study found that the correlation coefficients among tests were modest, suggesting that these techniques measure different neurophysiological parameters. The natural clustering of patients and healthy controls into specific subgroups suggests that variations in the population should be considered when selecting subjects for studies. The study also found that certain tests are more sensitive and specific for diagnosing neuropathy, while others are better at identifying subjects without neuropathy. The results suggest that a complex relationship exists between autonomic, large, and small nerve fiber tests in diabetic neuropathy.A cross-sectional study examined the relationships among neurophysiological tests in patients with diabetes. The study included 130 individuals: 25 healthy controls and 105 with diabetes, classified by the presence or absence of neuropathy. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation, along with neurological exams and symptom scores. Correlation and cluster analysis were used to determine relationships between neurophysiological tests. Results showed that neurophysiological tests were abnormal in patients with diabetic neuropathy compared to healthy controls and those without neuropathy. Correlations among tests varied widely, with some tests showing little to no correlation. A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical nerve fiber subtypes. The study concluded that different neurophysiological tests measure distinct parameters and are not interchangeable. However, only a small number of tests are needed to clinically differentiate individuals with neuropathy from those without. The natural clustering of patients and healthy controls suggests that population variations should be considered in future studies of diabetic neuropathy. The study found that nerve conduction studies, assessing large myelinated fibers, are widely used in clinical practice. Damage to small, unmyelinated nerves or autonomic fibers can be measured by quantitative sensory testing, autonomic testing, and laser Doppler flowmetry. The study also found that tests of large fiber function had higher sensitivity and specificity than small fiber or autonomic tests. The results showed that all tests of nerve conduction studies, 4 of 6 autonomic tests, and 9 of 11 quantitative sensation tests differentiated diabetic subjects with neuropathy from those without. Tests of cutaneous blood flow did not reliably differentiate diabetic subjects with neuropathy from those without. The tests with the highest sensitivity and specificity were the blood pressure fall during phase 2 of the Valsalva maneuver and the cold-pain detection threshold in the foot. The study found that the correlation coefficients among tests were modest, suggesting that these techniques measure different neurophysiological parameters. The natural clustering of patients and healthy controls into specific subgroups suggests that variations in the population should be considered when selecting subjects for studies. The study also found that certain tests are more sensitive and specific for diagnosing neuropathy, while others are better at identifying subjects without neuropathy. The results suggest that a complex relationship exists between autonomic, large, and small nerve fiber tests in diabetic neuropathy.