Effect of Physical Activity on Neurogenesis in Peripheral Diabetic Neuropathy Type-II Diabetes

Study Overview
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Brief Summary
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Approximately 425 million people worldwide suffer from diabetes, making it a global epidemic. Diabetes consumes 12% of the global health budget, addressing the disease and its complications. In Pakistan, the estimated prevalence of diabetes stands at 9.8%, affecting both males and females. Diabetic peripheral neuropathy is a common complaint that significantly impacts patients' quality of life. Neuropathy is prevalent in 40-55% of diabetes cases, and its incidence rises with age. Additionally, exercise can promote neurogenesis and the release of beneficial factors like BDNF, contributing to improved cognitive function and mood. Aerobic exercises are recommended for managing type 2 diabetes, while resistance training can improve glycemic control and muscle health. Further research is needed to understand the effects of physical activity on neurogenesis in diabetic peripheral neuropathy patients and gender-specific influences on glucose metabolism. The study aims to enhance peripheral neurogenesis, glycemic control, and sensory functions, ultimately improving the overall quality of life for patients.

Detailed Description
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The study design is a randomized controlled trial, and participants will be blinded to avoid interaction. A convenience sampling technique will be used, and the study will take place at Pakistan Railways Hospital and Quaid-E-Azam University. It will span two years after receiving approval. Inclusion criteria specify the type of patients eligible for the study, while exclusion criteria identify conditions that disqualify participants. Various data collection tools and tests will be used, including Neuropathy Total Symptom Scale (NTSS-6), Berg Balance Scale, HbA1c, nerve conduction studies, blood glucose level measurements, dynamometer, and questionnaires assessing quality of life. The study procedure involves participant recruitment, randomization into treatment and control groups, baseline assessments, and a 12-week intervention for the treatment group. This includes both aerobic exercise (treadmill) and resistance training for the lower and upper extremities. Control group participants will continue their regular medication.

Official Title
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Effect of Physical Activity on Neurogenesis in Peripheral Diabetic Neuropathy Type-II Diabetes

Conditions
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Type II Diabetes Mellitus With Neurological Manifestations

Intervention / Treatment
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* Behavioral: Phsical Activity
* Drug: Medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type-II Peripheral Diabetic Neuropathy Neuropathy Total Symptom Scale (NTSS-6)>6 loss of protective sensation to detect a 10-gram Semmes Weinstein Monofilament on either foot at one of four sites tested or a vibration perception threshold value of 25V or more at either foot's hallux Numbness or reduced ability to feel pain or temperature changes. Able to Perform 20 minutes per week >2 bouts of physical activity Tingling or burning sensation. Sharp pains or cramps. Increased sensitivity to touch Symptoms last ≥ 6 months HbA1c above 6.5% <12% Berg Balance Scale score 45-56 Exclusion Criteria: Patients with walking difficulty Retinopathy & poor vision Inability to engage in activity without assistance Peripheral vascular disease e.g. ABI <0.6 orthostatic hypotension, resting heart rate above 100 bpm any Cardiac Issues Any diagnosed neuro-psychological issue e.g. depression, dementia or anxiety Lower limb amputation,foot deformity or ulceration Acute injury Hip and Knee OA

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physical Activity (Combined Aerobic and Resistance Training)<br>Group A will perform aerobic and resistance exercises at a moderate level. Brisk Walk on treadmill 5 days/week with 40-70% of Vo2max (maximal aerobic capacity) 150 min/week 50-55% humidity and a room temperature of 24-25 °C will maintain. The subject will wear insole proper fitted shoes. Aerobic exercise will be conducted for a total of 30 minutes per session for 5 days for 12 weeks. This protocol will be followed by a 10-minute warm-up and cool-down. Followed by 10-15 minutes of resistance-based exercises at a moderate intensity of three sets with 15 repetitions of upper and lower limbs respectively i.e. Dumbbell biceps curl, Standing dumbbell triceps extension, Dumbbell stiff-legged deadlifts and Dumbbell squats Resistance loads will be 40-50% of one repetition maximum. The resting interval between resistance training sets will be < 1 min. | Behavioral: Phsical Activity<br>* Combined Aerobic and Resistance Training<br>|
| Other: Control Group<br>The control group will maintain their usual activity level, foot care, diet, and blood glucose diary on a regular basis. Continue the prescribed medication | Drug: Medication<br>* The drug will maintain their usual activity level, foot care, diet, and blood glucose diary on a regular basis. Continue the prescribed medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Derived Neurotrophic Factor (BDNF) | BDNF is a member of the trophic factors of nerve regeneration microenvironment and therefore involved in the regulation of nerve fiber regeneration and protection of neurons | Baseline to after 12th Week | 
| Nerve Growth Factor (NGF) | Nerve growth factor (NGF) is a neurotrophic protein essential for the growth, differentiation, and survival of sympathetic and sensory afferent neurons during development | Baseline to after 12th Week | 
| Vascular Endothelial Growth Factor (VEGF) | VEGF enhances nerve blood flow and oxygen supply by inducing angiogenesis, in response to nerve ischemia and hypoxia caused by Diabetic Periphral Neuropathy | Baseline to after 12th Week | 
| HBA1c | HbA1c levels are associated with increased severity of peripheral neuropathy in patients with diabetes mellitus. | Baseline to after 12th Week | 
| Nerve Conduction Study (NCS) | A nerve conduction study (NCS) can quantitatively detect peripheral nerve dysfunction, even in the pre-symptomatic stage of DPN onset. | Baseline to after 12th Week | 
| Berg Balance scale (BBS) | The Berg Balance Scale (BBS) is a widely used clinical assessment tool that measures an individual's static and dynamic balance abilities. It is not specific to diabetic neuropathy but can be used to assess balance in individuals with various neurological and musculoskeletal conditions, including diabetic neuropathy. | Baseline, after 4th week, after 8th week and after 12th week | 
| Neuropathy Total Symptom Scale (NTSS-6) | Neuropathy Total Symptom Score-6 Questionnaire (NTSS-6) is a valid instrument for assessing the positive symptoms of diabetic peripheral neuropathy (DPN). Graphic representation of pain. | Baseline, after 4th week, after 8th week and after 12th week | 
| Dynamometry lower limb | Dynamometry is a method used to measure muscle strength, and it can be particularly useful in assessing muscle strength in the lower limbs of individuals with diabetic neuropathy. | Baseline, after 4th week, after 8th week and after 12th week |