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Neurogenic abnormalities characterize overt diabetic state. However, how early is their appearance in the clinical course of the disease is unclear.In 26 normotensive and normoweight prediabetic patients, aged 45.2 ± 3.2 years (mean ± SEM), we assessed efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography), spontaneous baroreflex sensitivity, and a number of hemodynamic and metabolic variables, including homeostatic model assessment (HOMA) index. Measurements were compared with those obtained in a group of 30 healthy controls of similar age.For similar clinic and ambulatory blood pressure and BMI values, prediabetic patients displayed significantly greater MSNA values than controls, both when expressed as bursts incidence over time (33.3 ± 2.0 vs. 25.6 ± 1.2 bursts/min, P < 0.01) and when corrected for heart rate values (49.6 ± 1.9 vs. 36.7 ± 1.4 bursts/100 heart beats, P < 0.01). This neurogenic abnormality was associated with a reduced spontaneous baroreflex MSNA sensitivity (−3.20 ± 0.2 vs. −4.72 ± 0.2 a.u., P < 0.01) and significantly greater HOMA index values (3.73 ± 0.1 vs. 1.65 ± 0.1 a.u., P < 0.01). In the multivariate analysis, performed in prediabetic patients, MSNA values were directly and significantly related to HOMA index and inversely and significantly to baroreflex-MSNA sensitivity.These data provide evidence that sympathetic and reflex abnormalities are of early appearance in the clinical course of the diabetic disease. The adrenergic overdrive and the baroreflex impairment may thus participate at the disease progression, favoring the development of the hypertensive state and adversely affecting the disease prognosis.