Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy

Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments. This article discusses the latest advances in the mechanisms of diabetic sensorimotor peripheral neuropathy (DSPN) and painful DSPN, originating both from the periphery and the central nervous system, and outlines the emerging diagnostics and treatments. Key points Diabetic sensorimotor peripheral neuropathy (DSPN) is a common complication of diabetes mellitus that is associated with increased mortality, neuropathic pain, foot ulceration and lower-limb amputation. The mechanisms of DSPN are not fully understood but involve downstream injurious pathways associated with hyperglycaemia, dyslipidaemia and microvascular disease leading to neuronal inflammation, oxidative stress, mitochondrial dysfunction and cell death. There are no universally accepted disease-modifying treatments for DSPN; management is focused on optimizing glycaemic control, the achievement of cardiometabolic targets, and the prevention and/or treatment of diabetic foot complications. The reasons why some patients develop painless rather than painful DSPN are unknown; however, alterations in the peri