The Effect of Sugar on Wound Healing

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              Most diabetics know that high sugar levels diminish our body's ability to    
           heal.  But many don't understand why sugar has a detrimental effect, or the
       extent of the effect. 

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                         This is what this page is all about.  We'll try to provide a brief explanation of how      
                high blood sugar affects healing, both indirectly and directly, then provide a visual   
     example of the effect of hyperglycemia from a clinical situation.

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Circulation

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Over longer periods of time, high glucose (sugar) levels in the blood can adversely affect circulation.   For large vessels, high blood glucose levels can cause narrowing and calcification of the blood vessels (atherosclerosis), diminishing blood flow.  This is often called peripheral artery disease or PAD.  This may lead to arterial ulcerations or gangrene.  On its own, chronic high blood sugar levels may cause peripheral artery disease, but the effect is even more profound in diabetics who smoke. 

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High blood sugar can also thicken the layer of cells lining the walls of the smallest of blood vessels, the capillaries.  This thickening, which may develop even in cases where no peripheral artery disease is present and the arteries are open and allowing normal blood flow, diminishes the ability of nutrients and red blood cells (which carry oxygen) to pass through the vessels.  Oxygen is required for cells to produce energy, so lowering cellular oxygen levels may inhibit our cells ability to function.  This damage to the capillaries is known as microangiopathy, and it is a process somewhat unique to diabetes.

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Even the blood, itself, is changed in the presence of high blood sugar, with the viscosity or thickness of the blood often worsened.  This can create abnormal clots within the vessels.

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The combined effect of all this--the large vessel disease, the small vessel disease, and the abnormal thickening of the blood itself--is that there is less oxygen and fewer nutrients delivered to energize our cells.  Hence, with high blood sugar, our circulation may diminish enough that we may have a diminished ability to carry out normal functions, let alone heal or fight off bacteria.

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Controlling sugar and the cessation of smoking may improve the circulation, but some of these changes are likely to be permanent.  So the earlier the patient gets his sugar under control, the better.

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Neuropathy

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            We've talk about neuropathy at greater length on our neuropathy page, which can be found here.  There we discuss                    the effect of neuropathy on the creation of wunds.   But it's worth mentioning again here, as neuropathy can
                          have an adverse effect in healing wounds as well.  This is true in terms of the effect neuropathy has in                                            deforming the foot, creating pressure points (motor neuropathy).  It is true in terms of its effect on
                                           diminishing the body's ability to sense damage (sensory neuropathy). 

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                     But it's also true in terms of the adverse effect on circulation via autonomic neuropathy. 
                     Blood flow is at least partially controlled by nerve function, and an autonomic neuropathy
                     may result in diminished blood flow.  Even in those without discernible peripheral artery
                     disease and blood reaching the feet, an autonomic neuropathy may cause blood to be
                  shunted back away from the feet before it is able to be delivered to the cells at the capillary
               level.  This is true for the toes in particular. 

   

                               Autonomic neuropathy may also result in dry, cracked skin of the feet, or occasionally, overly wet skin.
                        This may compromise our body's barrier to the outside world and further diminish healing potential.

 

 

Immune System

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The immune system is also compromised in the presence of high blood sugar.  White blood cells, which fight infection, may be fewer in number and less active.  Further, bacteria thrive in the presence of increased blood sugar.  This combination of effects increases the odds of infection.  Fortunately, these changes are often not permanent.  Tight control of blood sugar can improve the immune system.

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Altered Ability to Repair Tissue

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The ability of tissue to repair itself is also compromised with high sugar levels.  This effect, too, can fluctuate with the degree of glucose control.  When the sugar is high, our body's ability to repair itself diminishes.  But when the sugar is controlled, the ability of the body to rebuild damaged tissue is improved.  The ability of our body to heal damaged tissue in the presence of high blood sugar is often times under-emphasized as an effect of high blood sugar.  So we've provided this clinical example to illustrate this effect.

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To the right is a photo of a woman's foot
follow amputation of the first and second
toes and metatarsals (the bones to which
the toes attach to the foot).  The amputation
was performed to treat an infection, and the
photograph was taken at her initial visit to us. 

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It could be argued that removing two of the
foot's five metatarsals does not leave a 
stable foot mechanically, and perhaps the
patient might have been off with another
procedure.  But the discussion here is
wound healing, and the salient issue here is
that the chosen procedure left the patient
with a wound on the side of the left foot. 
 

Luckily, the location of the wound means it
is not subject to weight bearing pressures
like most diabetic wounds.  This allows us
to know that the process of healing seen in
these photographs is not a result of weight
bearing pressure.

 

The wound above right had been treated with dressing changes three times per week for

eleven months.  There was no debridement.  The patient had been told the wound

was healed,and there was just a callus (the thick layer of dead skin) remaining. 

However, as you can see, the wound site doesn't look quite normal.  The

callus is irregular and discolored.  And, calluses can mask problems

that may be present below, so the calluses should be removed,

something known as debridement. 

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In this case, when debridement was performed, the thick

skin just flaked off as a single unit, revealing an open

wound that extended down to bone (right). 

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Further, beside visible bone, we can see a

sinus tract (a hole) beneath the bone. 

 

When probed, that sinus tract

extended up beneath the bone

over an inch.  If the wound became

infected, that tunnel would provide a

highway for bacteria that would extend

directly up the leg. 

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So the wound wasn't, in fact, healed.  The

wound simply had a crust lying on top of it. 

The situation was a disaster waiting to happen. 

And the danger would not have been identified

if the callus hadn't been debrided.

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The majority of wounds with bones exposed

like this will develop an infection of soft tissue

or bone.  However, in this case, x-rays were

negative and there were no clinical signs of

infection.  So no antibiotics were initiated. 

However, they were considered, and one

could certainly  have argued fortheir use in

this case as a precaution.

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Local wound care was initiated.  This primarily
consisted of cleansing the wound, weekly 
debridement of abnormal tissue and a proper
dressing. Footwear was prescribed that placed
no pressure on the wound.

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​In the photograph to the right, you can see how
the wound looked ten days later.

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The wound looks somewhat improved. Some
redness (erythema) is seen around the wound,
but the redness was localized and not expanding. 
 

There bone is still exposed, but there was no

pus, no foul smell, no increased temperature.

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To the right we see the wound at three weeks.

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The wound is markedly improved from the
initial presentation.  The bones are no longer
exposed.  There are still no signs of infection.  

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Here is the foot at week four.

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The general guideline is that we'd like to see
40% improvement in a wound within 4 weeks. 
If you can, over 90% of wounds will be healed

within 12 weeks.

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This wound certainly meets this metric.

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To the right we see the wound at five weeks.

 

Looking a bit better compared to week four

--although the pace of healing appears slowed.

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A week later, at week six, the wound does

not look to have improved much from the

previous week.  In fact, it looks a bit worse.

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The patient shows no signs of an infection in
the foot.  However, she did have a small

infection in a catheter tube in her chest.  It

was thought this may have been the issue.

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The tubing was removed, and the  patient
was placed on antibiotics.

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To the right we see the foot at week seven. 

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The catheter tube infection appeared to be

resolved in the chest.  However, the foot
wound showed no improvement.  In fact,
it may look a little worse.  

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The patient stated she checked her sugar
regularly, and indicated it ranged from
6 - 8 mmol/L (that's 106-145 mg/ml for
our American friends reading this).  That's

not a bad sugar level for healing.

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Besides fighting the infection, the patient
stated she had been on her foot more of
late, and felt this was the reason for the
pause in her healing progress.

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Yet at week eight, we again see no real

improvement in the foot wound.

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In fact, the lower margin of the wound tissue

looked somewhat irregular and disorganized.

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After the initial four weeks, we had drastic
improvement, but we've regressed over the
following four weeks.

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At week 9, to the right, the wound looked no
better.  The skin color looks quite pale here,
but this is an artifact of lighting.  In reality, the
skin color was largely the same as the other
photos in this series. 

 

Nonetheless, the wound is foundering.  

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While the patient indicated her sugar was still
well controlled, we drew blood to assess both
blood sugar and nutritional status.  

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To the right we see the wound at its worst,
at week 10. 

 

The blood sugar level had come back at 16, 

(288 in US units).

 

At this point he patient admitted her sugars had

been ranging in the 12-16 range (216-288 US)
over the past several weeks.

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The patient indicated the sugar had gotten a
bit out of control because she had been eating
a lot of scones.

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When we look at the wound site more closely, we see that the
wound is wet (hyperidrotic), and overgrown (hyperproliferative)

with disorganized cells growing haphazardly. 

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The cells are undifferentiated, meaning it is hard to distinguish

any different types of cells, and the wound looks disorganized.

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Why Does The Wound Like This?

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In this case, the circulation to the foot over these 10 weeks was unchanged.  The degree of neuropathy and immune function hadn't changed much in that time either.  And with the wound located on the side of the foot, the changes in the appearance of the foot aren't likely associated with excessive pressure of weight bearing.

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Instead, the cause of this abnormal appearance is the one factor that has varied during these ten weeks--her high blood sugar. 

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To understand how an elevated blood sugar can make a foot look like this, it's important to know that when the body repairs a wound, there are cells that build up and repair the tissues in the wound--cell  construction specialists.  And there are cells that remove the debris that doesn't belong--waste management specialists. 

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On the construction side of the equation, the 

builders, are the cytokines and growth factors. 

These are hormones and polypeptides secreted

by nearly all cells in a wound—like neutrophils
and macrophages (which fight infection),
fibroblasts (which ceate new tissue), and
keratinocytes (cells that produce the protein that
makes skin. 

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Cytokines and growth factors are responsible for

controlling the growth, differentiation, migration,
metabolism, protein synthesis and the sequence
of wound healing. 

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The cells that close the wound--fibroblasts and 

skin cells are all directed by cytokines and growth
factors.  High sugar alters the ability of these to
function in an organized, synchronized manner.

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On the side of waste management are MMPs and TIMPs, along with macrophages.

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MMPs (Matrix Metalloproteases) are a group of over twenty structurally-related enzymes (such as collagenases, elastases, gelatinases, and serum proteases) that break down un-needed proteins in the wound site, the remnants of damaged tissues. 

 

MMPs depend upon calcium and zinc to function properly, so you can see why circulation delivering nutrients is important. 

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And as MMPs are enzymes (a substance), not cells, they need to be regulated. 

 

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TIMPs (or Tissue Inhibitors of Metalloproteases) are proteins that monitor and regulate the MMPs.  In chronic wounds with high sugar, the ratio of MMPs to TIMPs can become unbalanced, with MMPs becoming excessive. This results in the MMP

enzymes getting out of control, breaking down not only waste products, but healthy tissues. 

 

(Abnormal function of matrix metalloproteases are often seen in certain cancers.)

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Another factor on the waste management side of the equation are macrophages.  Macrophages are roving cells best known for chasing down and killing bacteria.  But they also help dissolve damaged and nonviable tissue.  Long-term high blood sugar has the opposite effect on macrophages as it does on TIMPs.  It reduces the macrophages ability to function.  Not only does this affect wound healing, but it is one reason diabetics have a more difficult time fighting off infections.

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The net result of all this is chaos in the wound cite.  Cells are being built randomly and irregularly, without any organized plan or oversight.  It's like a series of individual carpenters hammering and nailing together a small portion of a building with no blueprints, without consulting each other, and no one overseeing the construction. 

 

Yet other workers are aimlessly and haphazardly breaking apart

construction, tissue, without concern whether what they're taking

apart is solid, new construction holding the building together, or

whether it is old, waste product.
 

​​​With this in mind, we can look back at the wound and appreciate

what is happening.  Irregular and disorganized tissue is growing

erratically and indiscriminately, up and out of the wound.  The

cellular regrowth is without design or purpose.  It's hard to tell

which cells are young, fresh and productive and which are old,

weak and dysfunctional. 

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This is  good visual evidence for what high blood sugar can do

to a wound that was otherwise healing without issue.

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And this is the type of abnormal cellular function that's going on

inside the body when your sugar is elevated.

 

 

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Getting back to this case, a frank discussion was had with the patient that she was at grave risk if she didn't get her sugar

under control. 

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We arranged for a dietician.  Her primary care physician was consulted, though when the patient vowed to control her diet, no change in her medication was made.

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The patient returned a week later, week 11.  

Blood sugars were running in the 5-9 range
over the week.

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The wound had improved immensely in that 

week.

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At week 13, the wound is better still.

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Nearly closed at week 14.

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And here is the foot fully healed.  

 

The ulcer never again broke open during

the remainder of her life. 

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This case illustrates that with all treatment protocols held constant, with all other factors associated with healing (circulation, neuropathy, immune system) remaining constant, and with a wound in a location where alterations in weight bearing are not a factor, controlling hyperglycemia significantly improves wound healing. 

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And a lack of blood sugar control causes a wound to languish.

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