Editor's note: Diabetic neuropathy is the most common chronic complication of diabetes, and early screening and diagnosis and early intervention are of great significance to improve the prognosis of patients. At the 2024 Academic Conference on Diabetic Neurological Complications and Related Diseases of the Chinese Society of Diabetes held recently, Professor Lu Bin from Huadong Hospital Affiliated to Fudan University gave a wonderful talk on the topic of "Full Management of Neurological Complications of Type 2 Diabetes Mellitus (T2DM)".
1. Current situation: T2DM neuropathy and diabetic peripheral neuralgia have a high incidence and great harm
01 Half of the patients with DSPN often have no obvious symptoms in the early stage, which is abnormal on clinical examination
Neuropathy is the most common chronic complication in patients with T2DM in mainland China, with a reported prevalence of 61.8% [1], which is the main disease burden of diabetes, and neuropathy often co-occurs with other complications of diabetes. Distal symmetric polyneuropathy (DSPN) and autonomic neuropathy are the predominant types of diabetic peripheral neuropathy [2], and focal neuropathy, including mononeuropathy and radiculopathy, is relatively uncommon.
DSPN is one of the most distressing and costly of all chronic complications of diabetes, seriously affecting the quality of life of patients. First, DSPN is one of the main risk factors for diabetic foot, which is the leading cause of hospitalization and amputation in diabetic patients. Second, DSPN leads to increased healthcare costs, with more than $10 billion per year spent on diabetic neuropathy and its associated complications; Finally, DSPN can lead to serious mental illness, including depression, anxiety, and sleep disorders.
If DSPN is not recognized, decreased foot sensation significantly increases the risk of diabetic foot. DSPN patients with typical symptoms are easy to detect and diagnose, and the most common early symptoms include pain and paresthesias, but about half of DSPN patients may be asymptomatic and often found abnormalities during clinical examination. Asymptomatic patients are recommended for screening and diagnosis by physical examination, and neuroelectrophysiological testing is available if available (Figure 1).
Figure 1. Symptoms and clinical examination items of DSPN
02 The occurrence of diabetic neuropathy is closely related to the course of T2DM, age and blood glucose control
A domestic study [3] found that age, duration of diabetes mellitus, and HbA1c were risk factors for DSPN through binary logistic regression analysis. A foreign logistic regression analysis study [4] showed that unemployment, cardiovascular disease, dyslipidemia, diabetic retinopathy, and the course of the disease ≥ 5 years were significantly associated with DSPN. A cross-sectional study of HbA1c variability and DSPN in patients with T2DM [5] showed that diabetic peripheral neuropathy was significantly associated with long-term glycemic variability in T2DM, and that the proportion of patients with DSPN increased with increasing HbA1c variability (P<0.001).
03The pain caused by DSPN seriously affects the quality of life and work ability of patients
Diabetic neuropathy is often associated with pain, and the severity of pain is significantly correlated with the course of diabetes. The study found [6] that 13%~35% of patients with diabetic neuropathy have pain, which is called diabetic peripheral neuralgia (DPNP). In a European study [7], a European study [7] surveyed 3956 patients with neuropathic pain with 413 physicians from France, Germany, Italy, Spain, and the United Kingdom to analyze the direct and indirect costs of neuropathic pain, as well as its impact on quality of life and ability to work. The results showed that the score of daily activity interference in patients with neuropathic pain was 3.92~4.85, and the impairment of work ability reached 35.3%~58.3%.
2. Management: Methods for the full management of T2DM neuropathy and diabetic peripheral neuralgia
01DSPN is critical to manage the entire process
Both the latest ADA [8] and CDS guidelines [9] recommend that all patients should be screened for diabetic neuropathy at the time of diagnosis of T2DM, and then at least annually thereafter. DSPN is diagnosed by symptoms, signs, and ancillary tests.
The Chinese guidelines for the prevention and treatment of T2DM (2020 edition) propose tertiary prevention of T2DM [9]: 1) primary prevention: prevent the occurrence of T2DM in people without diabetes; 2) secondary prevention: in patients with diagnosed diabetes, prevention of future complications; 3) Tertiary prevention: Diabetic patients have already developed complications to prevent future disability or death.
Tertiary prevention with T2DM shows that full management of DSPNs is critical. The whole process of DSPN management includes: prevention of DSPN, timely diagnosis of DSPN, and comprehensive treatment of DSPN (including treatment for etiology/pathogenesis and pain treatment).
02DSPN Prophylaxis – Blood Glucose Control and Patient Education
Glycemic control: For type 1 diabetes mellitus (T1DM), glycemic control can prevent the development of DSPN, and although the strength of evidence for T2DM is not as strong as that for T1DM, it is still recommended for patients with newly diagnosed, young, and T2DM with no serious complications or comorbidities to aggressively control blood glucose at an early stage to reduce the risk of diabetic complications.
Patient education: All people with diabetes should receive diabetes self-management education to acquire the knowledge and skills needed for self-management. One of the priorities for educating DSPN patients is the importance of good foot care, proper footwear, and annual foot exams.
03Timely diagnosis of DSPN
A combination of five tests, ankle reflex, pinprick pain, vibration, pressure, and temperature, is recommended in clinical practice to screen for DSPN (Figure 2). Acupuncture pain and temperature sensation often reflect small fiber nerves, and ankle reflexes, vibration, and pressure sensation often reflect large fiber nerves.
Figure 2. DSPN Diagnostic Flow Chart
04DSPN Comprehensive Treatment
The comprehensive treatment of DSPN includes treatment of the cause, treatment of the pathogenesis of neuropathy, and pain management (Fig. 3).
Figure 3. Comprehensive treatment of DSPN
3. Recommendations: Medication recommendations for the full management of T2DM neuropathy and diabetic peripheral neuralgia
01Blood sugar control
Ideal glycemic control should balance hypoglycemic efficacy, risk of hypoglycemia, and blood glucose fluctuations. The Chinese Guidelines for the Prevention and Treatment of T2DM (2020 Edition) point out that strict control of hyperglycemia and reduction of blood glucose fluctuations are the most important measures for the prevention and treatment of T2DM neuropathy.
02Targeted treatment
Treatment of diabetic neuropathy should focus on the etiology and pathogenesis of neuropathy (Fig. 4).
Figure 4. Diabetic neuropathy is classified as a drug for the treatment of causes
03Pain Management
In recent years, China's 2018 Expert Consensus on the Diagnosis and Treatment of Diabetic Peripheral Neuropathic Pain [10], the Expert Consensus on the Diagnosis and Treatment of Diabetic Neuropathy (2021 Edition) [11], and the 2022 AAN Guidelines for the Treatment of Painful Diabetic Polyneuropathy with Oral and Topical Drugs [12] have been published one after another, recommending the screening, diagnosis, management and management processes and drug treatment of DPN including DPNP. Venlafaxine and amitriptyline are used as first-line agents.
IV. Conclusion
The incidence of T2DM neuropathy is high, DSPN is the main complication of neuropathy, DSPN has a high disability rate and is easy to cause psychological problems, and DSPN is often accompanied by pain, that is, DPNP, and the longer the course of the disease, the more serious the DPNP, which seriously affects the quality of life and work ability of patients. Neuropathy in T2DM should be managed from prevention and diagnosis to targeted treatment and pain treatment. In the choice of drugs for neuropathy, glycemic control, targeted treatment, and pain management need to be taken into account.
Expert Profile
Lu Bin
Huadong Hospital Affiliated to Fudan University
Director of the Department of Endocrinology, Executive Director of the Center for Rare Diseases
Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor
Leader of the health discipline of the Shanghai Municipal Health Commission
He is a member of the Shanghai Diabetes Society and the leader of the neuropathology group
Member of the Standing Committee of the Tumor Endocrinology Committee of the Chinese Anti-Cancer Association
Member of the Standing Committee of the Endocrinology Professional Committee of the Chinese Association of Integrative Medicine
Member of the Neurological Complications Group/Epidemiology and Prevention Group of the Diabetes Branch of the Chinese Medical Association
Member of the Neurology and Endocrinology Group of the Endocrinology Branch of the Chinese Medical Association
He has presided over 4 projects of the National Natural Science Foundation of China, and published 36 SCI papers as the first author/corresponding author; Participated in the compilation of 6 monographs on practical internal medicine;
Funded by Shanghai Talent Development Fund, Second Prize of Shanghai Science and Technology Progress Award/Chinese Medical Science and Technology Award (Second Completer)
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