Painful Diabetic Neuropathy Linked To Higher Nocturnal Blood Pressure Interview with:Vincenza Spallone MD PhD Endocrinology and Neurology Department of Systems Medicine Tor Vergata University, Rome, Italy
Vincenza Spallone MD PhD

Endocrinology and Neurology
Department of Systems Medicine
Tor Vergata University, Rome, Italy

Medical Research: What are the main findings of the study?

Dr. Spallone:To investigate a possible relationship between painful diabetic polyneuropathy (PDPN) and the circadian pattern of blood pressure (BP), we performed ambulatory blood pressure monitoring in 113 diabetic patients with PDPN, with painless diabetic polyneuropathy (DPN) and without DPN. In addition, we evaluated neuropathic pain, sleep, risk for obstructive sleep apnoea (OSA), autonomic function, and in a subgroup of patients, depressive symptoms.

The main finding was that patients with painful diabetic polyneuropathy displayed impaired nocturnal fall in BP compared to those without neuropathy, and higher nocturnal systolic blood pressure than the other two groups. Although the day-night change (∆) in blood pressure failed to reach a significant difference between painful diabetic polyneuropathy and DPN groups, nondipping (the loss of nocturnal fall in systolic BP) was more strictly associated with painful diabetic polyneuropathy than DPN and in multivariate analysis, including comorbidities and most potential confounders, neuropathic pain was an independent determinant of ∆ BP and nocturnal systolic blood pressure.

In summary, we showed a novel association of peripheral diabetic neuropathic pain with nondipping and higher systolic nocturnal blood pressure, which was not entirely explained through pain dependent sleep problems or other pain- or diabetes-related comorbidities, like CAN, OSA and depression.

Medical Research: Were any of the findings unexpected?

Dr. Spallone: Pain-dependent sleep disturbances were a rather expected finding, even though previous studies lacked a comparison between patients with painful and painless DPN. Here, we confirmed the negative impact of neuropathic pain on sleep and provided the finding of a peculiar link between diabetic peripheral neuropathic pain and sleep behaviour independently on possible influences of neuropathy and diabetes per se.

Nondipping and reverse dipping patterns have been reported to be associated with CAN and linked to a disruption of the circadian variation in sympathovagal activity, i.e. a diminished increase in vagal activity during the night with a consequent sympathetic predominance. Nondipping has also been associated with short sleep duration in patients with diabetes and with OSAS in the general population. Thus, it was not obvious that the PDPN was related to nondipping and night-time BP independently from CAN influence and from the presence of sleep problems and high OSA risk. This finding possibly suggests that, in patients with painful diabetic polyneuropathy, nocturnal pain itself acts as a stressor by inducing a sympathetic response during the night with a consequent exacerbation of the pre-existent sympathovagal unbalance (associated with autonomic dysfunction secondary to diabetes and to chronic pain) and thus inhibiting BP fall during the night.

Medical Research: What should clinicians and patients take away from your report?

Dr. Spallone: We think that the finding of an association between painful diabetic polyneuropathy and both nondipping and higher night-time BP could be of clinical relevance given the independent prognostic value of these two BP features for end-organ damage and cardiovascular morbidity and mortality in the general population and even more in diabetic population. The prognostic burden represented by nondipping and higher night-time BP increases the negative prognostic value already constituted by diabetic neuropathy itself and other comorbidities of chronic neuropathic pain, as sleep loss and disturbance.

Painful diabetic polyneuropathy is common (with a prevalence of about 18%), and exerts a deep impact on sleep, mood, and quality of life. It is, however often undiagnosed and under-treated. This study indicates one more reason to pay attention to this diabetic complication and supports the view that diabetic peripheral neuropathic pain should increasingly be regarded as a condition of high cardiovascular risk. Chronic neuropathic pain in diabetic patients should be promptly recognized and properly managed to offer relief to patients and improve their cardiovascular risk profile.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Spallone: A logical development of this study would be to verify whether effective pain treatment can correct the abnormal BP findings, i.e. lowering night-time BP and restoring dipping status, and to ascertain whether and to what degree the potential beneficial effect on BP of pain relief is direct or mediated through sleep or mood changes.


A Novel Association Between Nondipping and Painful Diabetic Polyneuropathy
Cinzia D’Amato, Roberto Morganti, Federica Di Gennaro, Carla Greco, Girolama A. Marfia, and Vincenza Spallone
Diabetes Care published ahead of print June 26, 2014, doi:10.2337/dc14-0528 1935-5548


Last Updated on July 8, 2014 by Marie Benz MD FAAD