Reversing Diabetic Peripheral Neuropathy through exercise

• Grant number: 19/07563-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 25, 2019
• End date: April 04, 2020
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Tania de Fatima Salvini
• Grantee: Jean de Paula Ferreira
• Supervisor: Smita Rao
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: New York University, United States
• Associated to the scholarship: 17/09050-1 - Assessment of the passive and eccentric torque at knee and ankle flexion and extension in type 2 diabetics with and without peripheral neuropathy, BP.DR

Abstract

Background:Diabetes mellitus (DM) affects 26 million people in the US [1], with 30-50% of type-2 diabetes mellitus (T2DM) patients developing diabetic peripheral neuropathy (DPN) [2-4]. DPN is characterized by impairments of metabolic and microvascular (MV) functions [5], which damage the endoneural capillaries that supply the peripheral nerves [6]. Prolonged DPN can lead to local ischemic conditions in the lower extremities, causing loss of peripheral nerve integrity, neurogenic muscle atrophy, fatty infiltration [7, 8], and loss of muscle endurance [9-12]. These synergistically contribute to altered gait, impaired balance, and increased fall risk, which can lead to bone fractures, poorly healing wounds, and chronic infections [13-15] that often require an amputation [16, 17]. There are no therapies to prevent or reverse the progress of DPN [18-20]. Therefore, it is very important to establish effective treatments for DPN.Hypothesis:We hypothesize that DPN patients who undergo 10 weeks of exercise will show improved function, and that exercise will improve the structure, local metabolic, and MV functions of skeletal muscle. A major obstacle to assessing how DPN affects skeletal muscle and peripheral nerves is the lack of sensitive, objective, and reproducible tests to detect small changes in muscle and nerve functions [10]. Multinuclear-MRI can bring new insights into how DPN affects skeletal muscle function [31-33]. Our group has developed novel phosphorus (31P)-MRI techniques that can reliably assess skeletal muscle metabolic function [34, 35], as well as rapid techniques to quantify blood oxygenation level dependent (BOLD)-MRI signals, sensitive to MV function [36-38] and its adaptations after exercise interventions [39]. Finally, we will use IDEAL-MRI to quantify levels of intramuscular adipose tissue (IMAT), which are elevated in DPN [47-50]. We will prescribe a 10-week exercise program, with both aerobic and resistance components [14, 24], to 40 DPN patients who will receive personal supervision from health professionals. We will acquire multinuclear-MRI data at three time points: 1) baseline, 2) pre-intervention and 3) post-intervention. DesignThis single-center, cross-over design study uses multinuclear-MRI to evaluate the mechanistic effects of exercise on skeletal muscle function and peripheral nerve integrity in patients with DPN, and to determine whether exercise can reverse DPN symptoms. Forty DPN patients will be enrolled and be prescribed a 4-week non-exercise period followed by a 10-week exercise program. The exercise program will comprise aerobic and resistance components; a moderate level of intensity will be calculated based on results from a maximal graded exercise test (VO2R) conducted prior to the intervention. Multinuclear-MRI data will be acquired at baseline and before and after the intervention that can provide mechanistic insight into the adaptations in lower leg muscle function and peripheral nerve integrity of patients with DPN, and their role in improving DPN symptoms.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, JEAN P.; ARAUJO, VANESSA L.; LEAL, ANGELA M. O.; SERRAO, PAULA R. M. S.; PEREA, JULYA P. M.; SANTUNE, AFONSO H. A.; PON-JUNIOR, HENRIQUE; FERNANDES, RICARDO A. S.; ARANHA, GABRIEL D. A.; SACCO, ISABEL C. N.; et al. DIABETES AND PERIPHERAL NEUROPATHY ARE RELATED TO HIGHER PASSIVE TORQUE AND STIFFNESS OF THE KNEE AND ANKLE JOINTS. KINESIOLOGY, v. 54, n. 1, p. 13-pg., 2022-06-01. (19/07563-7, 18/14610-9, 17/09050-1)