Abril - 2017

eripheral

polyneuropathy

severely

obese

patients

with

metabolic

syndrome

but

without

diabetes

: A

ssociation

with

low

HDL-

cholesterol

ssoc

ras

2017; 63(4):324-331

329

erides with lower limb amputation, but no association

with LDL and HDL-cholesterol.

We observed that, al-

though there was initially a significant association be-

tween serum levels of LDL-cholesterol and a tendency of

association between serum triglyceride levels with the

presence of PPN, this association was not confirmed in

the multivariate regression.

Our study raised the hypothesis that non-diabetic

Ob-II,III,MetS patients and with PPN would have lower

levels of vitamin B12 compared to those without PPN

and that there would be an association with the use of

metformin, since some pre-diabetic patients receive this

prescription in order to prevent progression to DM. How-

ever, the results showed no association between the pres-

ence of PPN and vitamin B12 levels or use of metformin.

Since we showed a significant prevalence of PPN in

severely obese subjects with MetS without diabetes and

a significant association of PPN with low HDL-choles-

terol, we considered this finding as the most consistent

in our study and we will make some considerations about

this possibility.

In addition to being a marker for future

or concur-

rent

cardiovascular disease, low HDL-cholesterol is also

associated with many clinical parameters such as low lev-

els of physical activity.

Thus, the main recommendation

made to increase HDL-cholesterol is physical exercise.

23-25

Since a study conducted by our research group showed

that 1 year of Roux-en-Y gastric bypass decreased serum

levels of blood glucose, total cholesterol, LDL-cholesterol

and triglycerides, but did not improve HDL cholesterol,

it is also possible that PPN described after this kind of

bariatric surgery by other authors

could be related to the

low HDL-cholesterol levels that these sedentary patients

usually present, as well as to vitamin deficiency.

Clinical and epidemiological studies have shown that

HDL, a class of plasma lipoproteins, can be very hetero-

geneous in size and density, and have an atheroprotective

role attributed to its ability to promote efflux of choles-

terol from arterial macrophages loaded with cholesterol.

28,29

However, recent studies have recognized great physical

heterogeneity of HDL, which is associated with its mul-

tiple functions. Both the protein and lipid components

of these particles are involved in its effect. The apolipo-

protein AI (ApoA-I) is quantitatively the major protein

constituent having a structure suitable for transporting

lipids. It readily interacts with the ATP-binding cassette

transporter A1 (ABCA1) and the scavenger-receptor B-1

(SR-B1), and it activates the enzyme lecithin-cholesterol

acyl transferase (LCAT), which is essential for HDL mat-

uration. The resulting primary mature particles are HDL2

and HDL3. Moreover, ApoA-1 has antioxidant and anti-

-inflammatory properties, together with other enzymes.

Regarding lipid fraction, an atheroprotective role has been

recognized for lisosphingolipids, particularly sphingosine-1-

-phosphate (S1P), which is involved in the process of cho-

lesterol reverse transfer. All these atheroprotective func-

tions are apparently lost in the plasma of patients with

systemic inflammation, coronary heart disease, diabetes

and chronic kidney disease, as these patients’ plasma is

considered dysfunctional.

28-30

When HDL-cholesterol

levels are low, as observed in our patients classified as

neuropathic, the atheroprotective effect of HDL-choles-

terol is probably also decreased.

On the other hand, it has been observed in vitro that

HDL-cholesterol particles can be captured by injured

distal axons and used for the regeneration of these fibers.

If the uptake of HDL from plasma through binding with

SR-B1 receptors previously described as present in distal

axons also occurs in vivo, lower peripheral axonal regen-

eration can take place in patients with low HDL-choles-

terol, which would explain our findings.

Increased physical activity of animals has been as-

sociated with better autonomic function and could prevent

the decrease of nerve function related to aging when they

exercise on a regular basis.

32,33

In humans, in whom the

presence of denervation was assessed by skin biopsy and

study of intra-dermal nerves, it was observed that lifestyle

changes (exercise and diet) determined not only improve-

ment of the lipid abnormalities but also an increase of

nerve fibers density in a subsequent biopsy.

34,35

These data,

as well as the findings of our study, suggest that HDL-

-cholesterol could be either a mediator involved in this

effect or a marker that indicates little physical activity,

genetic predisposition to atherosclerosis, and other al-

terations, for example, increased oxidative stress (which

would favor neuronal dysfunction). If our findings are

later confirmed in studies with other population samples

and other designs, there would be a common explanation

for the etiology of neuropathy in sedentary subjects, es-

pecially when they are obese, with MetS and/or with DM2.

In our study, no difference was found between men

and women for the presence of PPN and other studied

variables. The low number of men with PPN in our sam-

ple population limited our evaluation. Increasing the

number of men in the neuropathic group would allow us

to analyze if all associated factors found would associate

in both sexes or if any of these would prevail in male or

female. Since men have a mean HDL-cholesterol level

lower than that of normal women, it is possible that the

higher prevalence of neuropathy and amputations found