Effect of Exercise and Surgical Weight Loss on Polyneuropathy

Intraepidermal Nerve Fiber Density (IENFD) as assessed by 3mm skin biopsies at the proximal thigh.

Intraepidermal Nerve Fiber Density (IENFD) as assessed by 3mm skin biopsies at the distal leg.

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology.

Corneal Nerve Fiber Density are quantified by fibers/mm2, a higher number represents a higher density of fibers. Lower numbers indicate worse neuropathy.

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology.

Corneal Nerve Branch Density are quantified by branches/mm2, a higher number represents a higher density of branches. Lower numbers indicate worse neuropathy.

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology.

Corneal Nerve Fiber Length are quantified by mm/mm2, a higher number represents a higher total length of fibers. Lower numbers indicate worse neuropathy .

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology.

Tortuosity Coefficient represents the total tortuosity (twisting/bending of nerves). As a coefficient the value is unitless, a higher value represents greater tortuosity. Lower numbers indicate worse neuropathy.

24-2 FDT was used to evaluate retinopathy using visual field deficits. Mean Deviation is presented below.

Mean deviation is the average difference from normal expected value in the patients' particular age group. Lower values indicate more visual deficit. Higher values indicate fewer visual deficit.

24-2 FDT was used to evaluate retinopathy using visual field deficits. Foveal sensitivity is presented below.

Foveal sensitivity is the measurement of the fovea's light detection ability. Lower values suggest visual field deficits.

24-2 FDT was used to evaluate retinopathy using visual field deficits. Pattern SD (PSD) is presented below.

PSD provides information about localized loss. A higher PSD indicates a non-uniform sensitivity loss and visual field deficit.

As assessed by fundus photographs, participants were identified as either having retinopathy or not having retinopathy. Data is shown as number of people with retinopathy at a particular study visit.

Latency measures the time in millisecond between stimulation and the recording electrode. Was performed on sural, peroneal, and tibial nerves. No response and abnormal values indicate neuropathy.

• Peroneal: 0 - No response, >6.5 - Abnormal
• Sural: 0 - No response, >4.5 - Abnormal
• Tibial: 0 - No response, >6.1 - Abnormal

Amplitude measures the height of electrical signal (waveform) in millivolts produced by the stimulated motor nerve. Was performed on peroneal, and tibial nerves. No response and abnormal values indicate neuropathy.

• Peroneal: 0 - No response, < 1.1 - Abnormal
• Tibial: 0 - No response, <1.1 - Abnormal

Amplitude measures the height of electrical signal (waveform) in microvolts produced by the stimulated sensory nerve. Was performed on sural nerve. No response and abnormal values indicate neuropathy.

• Sural: 0 - No response, <4 - Abnormal

Conduction velocity (V) measures the speed (m/s) at which the electrical impulse travels along the nerve. Was performed on peroneal nerves. No response and abnormal values indicate neuropathy. Abnormal values are <36 or 39, depending on whether certain criteria applied to the participant. Data was not analyzed separately.

F wave index measures the time in millisecond between stimulation at a distal (near the muscle) point and for the stimulus to travel to the spinal cord and back, allowing to assess the entire length of the nerve.

Was performed on peroneal, and tibial nerves. No response and abnormal values indicate neuropathy.

• Peroneal: 0 - No response, >55 - Abnormal
• Tibial: 0 - No response, >55 - Abnormal

Deep breathing/exhalation to inhalation (E:I) ratio were evaluated using PS monitor software. Values < 1 are abnormal, indicative of cardiovascular autonomic neuropathy

Postural change-30:15 ratio was evaluated using PS monitor software. Values < 1 are abnormal, indicative of cardiovascular autonomic neuropathy

Valsalva ratio was evaluated using PS monitor software. Values <= 1.10 are abnormal, indicative of cardiovascular autonomic neuropathy

Toronto definition of probable neuropathy is having at least 2 out of 3 of the following: abnormal sensory examination, reflexes, and patient-reported symptoms. Data is reported as number of participants who, under the Toronto definition, were identified as having probable polyneuropathy.

MNSI questionnaire is scored from 0-15, score > 4 indicate neuropathy, higher scores indicate worse neuropathy.

A score of 1 point is given for answers of "yes" for questions 1-6, 8-12, 14, and 15 and "no" for questions 7 and 13.

MNSI exam is scored from 0-8, score >= 2.5 indicate neuropathy. Higher scores indicate worse neuropathy.

The Michigan Neuropathy Screening Instrument (MNSI) index is a weighted composite score computed using the sum of the b-coefficients for all items within the MNSI questionnaire (15 questions) and MNSI exam (4 physical/visual exam).

Range: -0.93, 7.39 Values > 2.5407 are indicative of clinical neuropathy

UENS is a composite score with five sections measuring multiple clinical measures of nerve injury. Sections are scored separately for each side (Right vs Left), and the total score is the sum across everything. Range: 0-42, higher score represents more severe polyneuropathy.

mTNS is a scale of 0-33 that measures neuropathy symptoms and exam findings. Higher scores indicate more severe polyneuropathy.

SAS evaluates the presence and magnitude of autonomic symptoms. Total impact score ranges from 0-60 (or up to 55 for participants to whom certain criteria did not apply). Higher score indicates worse autonomic neuropathy

DNS is a questionnaire of neuropathy symptoms. Score ranges 0-4, >/=1 indicates polyneuropathy. 0 indicates no polyneuropathy.

Sum of the sensory score (0-30) and affective score (0-15) for a total score of 0-45. A higher score represents greater pain present.

Participant reported pain scale with range 0-10, higher score indicates more pain.

Neuropathy Quality of Life (NeuroQOL) evaluates symptoms and function in regard to quality of life over the past four weeks. Range 1-15, higher score indicates neuropathy having a greater impact on quality of life.

This test measures in seconds how long it takes the participant to stand up from a seated position, walk around a cone places 8 feet away, and return to the chair and sit down. Less time indicates better speed, agility, and balance when moving.

Berg Balance Scale measures participants' ability to balance and avoid falls. Scores range from 0-56, higher score indicates less likely to fall.

Patient response indicating if they have fallen in the last year. Data is shown as number of people who have fallen in the last year.

Neurothesiometer is placed on the bottom of the great toe, and slowly increased until participant reports they can feel the vibration. The greater the microns, the less feeling the participant has, suggestive of worse sensory function.

Value > 25 Microns is indicative of neuropathy. There is no known maximum range. Lower values indicate better sensory function.

NIH Toolbox Cognition Fluid (Range: 0-100) - Composite score derived as an average across five cognitive domains.

It's a fully adjusted T-score comparing the participant to a nationally representative sample, stratified by age and other demographics.

Individual domain scores are fully adjusted T score with range 0-100 and measures the following-

• Inhibitory Control and Attention - executive function, attention .
• Dimensional Change Card Sort - executive function
• Picture Sequence Memory - episodic memory
• List Sorting Working Memory - working memory
• Pattern Comparison - processing speed

A T-score of 50 represents the population mean. A score of 60 indicates that the participant is 1 SD above the national average for individuals with similar demographic characteristics

Higher scores reflect better cognitive functionality. No set clinical threshold, scores above mean indicate above average cognition for a given age group.

Used to evaluate verbal learning and memory using a list of 15 unrelated words presented to the participant over repeat trial.

Includes 3 independent scales:

• Auditory Learning (Total recall) - Measures memory and learning ability. Raw score range (0- 75)
• Delayed Recall - Measures long term memory retention. Raw score range (0-15)
• Recognition - Measures ability to recognize previously learned information. Raw score range (0-15).
• Raw scores were converted to age-standardized Z-scores using 10-year age bands (e.g., 20-29, 30-39, 40-49, etc.), with a mean of 0 and standard deviation of 1.
• A Z-score of 0 represents the population mean
• For each scale, scores above 0 are better. Standard deviations above the mean indicates a better learning and memory ability for a given age group.

No set clinical threshold, scores above mean indicate above average cognition for a given age group.