What is Glycation & How Does it Affect Our Skin?
1. How does high blood glucose contribute to problems in the skin?
High blood glucose leads to an excessive amount of “Advanced Glycation End Products” or AGEs. AGEs are formed when the excess glucose and glucose byproducts “glycate” or form permanent cross-links with proteins, lipids and nucleic acids.
Molecules such as collagen, elastin, the lining of blood vessels (even in the placenta), nerve tissues, optic lens tissue, and kidney tissue are particularly susceptible to glycation.
As you can imagine, when these proteins, lipids and nucleic acids in the various parts of the body become glycated, they become stiff, fibrotic and non-functional. The end result is atherosclerosis, alzheimer’s disease, neuropathy, kidney failure, cataracts, macular degeneration, preeclampsia and the dreaded wrinkle!
2. What are the common skin issues related to diabetes? Which ones are the most serious/dangerous? Common problems seen in diabetes include the following:
- Acanthosis Nigricans and Skin Tags: (Extremely Common) Acanthosis nigricans presents with a darkened velvety texture to the skin found on the back of the neck, the arm pits, the folds of the elbows and the backs of the finger tips. It is almost always accompanied by one or many skin tags. I explain this condition to my patients as the “canary in the coal mine’; it is your body’s way of telling you that you either have, or soon will have, type II diabetes if you don’t change your diet and lose weight. This condition is likely associated with excessive glycation.
- Diabetic Foot Ulcers and Sensory Neuropathy: (very common) a result of AGE-induced damage to sensory nerve fibers, the lower extrememties lose their ability to feel pain, pressure, heat and/or cold. The skin breaks down and is often traumatized without detection until infection has set in. This infection often leads to a chronic wound that also has difficulty healing due to AGEs.
- Diabetic Dermopathy: Thickened brown patches usually found on the shins. This condition is likely due to AGEs being deposited and damaging the skin.
- Scleredema Adultorum: (less common) is a thickening of the skin that starts on the back of the neck and can extend around the neck to include the upper shoulders, back and chest area. This too is a result of AGEs.
- Necrobiosis Lipoidica Diabeticorum: (uncommon) is yellowish-brown waxy plaque usually seen on the anterior shins and also likely due to AGEs.
Of all these conditions, acanthosis nigricans is by far the most common and affects many non-suspecting people who are pre-diabetic and diabetic. The next most common and the most dangerous is the diabetic foot ulcer with sensory neuropathy.
3. Which skin issues can you treat at home, and which do you need to seek medical help for?
All of the above conditions are relatively recalcitrant to treatment; however, the most responsive of all is acanthosis nigricans. It is only responsive to significant loss of weight or the correction of insulin resistance. Skin brightening products are less effective on this condition, however I have seen some benefits when using products that contain high concentrations of 18-B glycyrrhetinic acid.
I always emphasize the need to not obsess about losing weight but rather, to focus on increasing muscle mass in these patients. Muscle metabolizes sugar differently than fat does and can lead to longer-term benefits and decreased glycation product formation.
The broken skin barrier of the feet is by far the most important skin condition that can and should be addresses on a daily basis at home. A regular evaluation of the skin on the lower legs, ankles and feet for any cuts, scrapes or rashes is very important. An effective skin barrier repair product is also important to maintain healthy skin in this area.
4. Will over-the-counter skin creams help with these issues? What ingredients should they look for?
It is possible that over the counter products may help with the effect of glycation in the skin, however there is little evidence and there are no clinical trials that can give us definitive data. There are a few studies that show benefits of molecules in preventing or treating AGEs in the skin when applied topically.
There may be benefits to carnosine though it is found exclusively in animal tissues and animal tissues contain more AGEs in the first place. At any rate, one study showed that carnosine may be able to disaggregate glycated proteins (Seidler et. al., 2004), but this may not be a good thing as disagreageted glycation byproducts can be more harmful than their precursors.
Another study discussed the possible benefit of phenolics in white grape skins that are left over from the vinification process. (Sri Harsha et.al., 2014). Two vegetable molecules; puerarin and chorogenic acid might also be beneficial in the prevention of glycation. Gasser et. al., 2011).
There also appears to be a possible benefit of aspirin (salicylic acid) taken orally for over a year in the prevention of only one (of many) glycation byproducts. There is no evidence for/a paucity of data about the benefits to AGEs with the topical use of salicylic acid. (Contreras et.al., 1997) There may also be benefits from a molecule from mangoes called mangiferin which was shown to reduce the effects of AGEs and the genesis of fats in the body.(Mahali et. al., 2014)
DIET Is the Most Important Way to prevent Glycation in the Skin:
Most interesting and helpful, is the role of diet in the generation of AGEs in our bodies and our skin.
Studies have shown that increased temperature, an alkaline pH in our food, and a diet rich in animal-derived foods that are high in fat and protein will usually have significantly more AGEs and are able to make new AGEs more easily than fruits, vegetables, whole grains and milk. (Uribarri et.al., 2010).
Cooking foods at lower temperatures, in a moist environment (slow cooker) and at higher pH—by using vinegar or lemon, was also shown to dramatically decrease (by 200%) the concentration of AGEs in cooked meat!
We can possibly apply this same logic to the skin. If 200 percent fewer AGEs are made by acidifying food, it would likely behoove us all to maintain the acidic pH of the skin.
We do know that the optimum pH of the skin is 4.6 to 5.6 and thet ceramide production happens only in this range. Ceramides have been shown to prevent matrix metalloproteinase-induced collagen and elastin digestion.
Some acids are more effective and safe than others. My favorite acidification system for the skin is called pH-protect and is found in the TrueLipids products.
Gluconolactone is used because it does not have the dangers of alpha hydroxyl acids, it is a free-radical scavenger and antioxidant, it has been shown to repair some of the forms of DNA damage caused by UV radiation AND it is very effective at preventing water loss from the skin in addition to many other benefits to the skin.
The use of pH balancing products would be very beneficial and may likely decrease AGE formation as well. Foods that were cooked in an acidic environment have about 200 times fewer AGEs than when the same foods were cooked without an acidic marinade such as lemon juice or vinegar.
Also, increased heat, especially dry heat, used in cooking increases the number of AGEs in our food. From this we learn that it is also likely to be very beneficial to acidify the skin to prevent glycation products from forming.
5. What skin care regimen would you recommend in order to reduce the risk of skin-related problems in people with diabetes?
The most important skin care regimen includes tactics to protect and repair the skin barrier. The disrupted diabetic skin barrier has five points of vulnerability:
- Deficient lipid production
- Abnormal pH
- Susceptibility to infection
- Susceptibility to free-radical oxidative damage that leads to decreased glycolysis and increased glycation end products
- Chemical sensitivities
This applies not only to the skin of the feet but to the rest of the body as well. Increased concentrations of AGEs in diabetic skin inhibit wound healing and make a diabetic more prone to infection.
It is important for a diabetic to use products that maintain a healthy skin pH, that have free-radical scavenging capabilities (certain anti-oxidants), that have anti-inflammatory properties to prevent the formation of AGEs and that assist with skin barrier repair. The TrueLipids line of skin care products are the only products in the world that address all six problems of the susceptible diabetic and non-diabetic skin barrier.
These products recreate the natural environment in the skin where the skin anti-oxidant capabilities as well as skin barrier repair technology can be leveraged to help the skin to heal itself and to help to maintain a state of health and prevention of wrinkling at the same time.
6. Can you explain, in layman’s terms, how glycation and diabetes are related?
Glycation happens when glucose and glucose related molecules form permanent cross-links to proteins, lipids and nucleic acids. These glycation products are much more frequent in diabetics due to the elevated glucose in a diabetic. Glycation end products are more common in higher heat and in higher pH environments.
Diabetics are particularly susceptible to glycation as a result of excess glucose that circulates throughout the body as a result of insulin resistance. Glucose normally enters the cell with the help of insulin. When insulin is absent (Type I Diabetes) or if the cells are resistant to the effects of insulin (Type II diabetes and Polycystic Ovarian Syndrome), then the glucose is free to hang out anywhere in the body and form countless glycation products. This leads not only to damaged collagen and elastin in our skin, but also leads to damaged blood vessels, damaged nerve and kidney tissue, alzheimer’s disease and increased lipid production in the body.
7. How has diabetes research helped us to understand glycation and skin aging? Is this applicable to those who do NOT have diabetes?
Diabetes research has had a large impact in understanding the dangers of a high glucose diet in diabetic and non-diabetic skin alike. Having a sweet tooth can lead to excess glucose in the blood stream in diabetics and non-diabetics and is guaranteed to foster collagen and elastin breakdown and to accelerate the signs of aging.
Once you understand the dangers of AGE formation, it makes it a little easier to walk away from the Cadbury® mini eggs at Easter, the candy bars at Halloween and the baked goods at Christmas!
Sugar is subject to glycation in everyone and the more sugar there is, the more likely that glycation and its complications are to happen. Research on glycation prevention and glycation eradication after they have been formed is greatly needed.
This field is beginning to open up and give us some very interesting and useful information that will continue to tell us what products will help or hurt our skin from a glycation stand point. Overall, the most effective treatments include anti-oxidants, anti-inflammatory molecules, low pH systems and skin barrier repair-based products.
To learn important tips and tricks for the best care for diabetic skin, please go to our Diabetic Skin Care Page.