Psoriasis as a risk factor for type II diabetes
by Ed Anderson Sept 20, 2000
In recent years, there has been persistent promotion of a hypothesis by Gary R Jackson that psoriasis is the result of widespread subclinical insulin resistance. Unfortunately, the deluge of references and connections he has presented in thousands of often ad hominem posts do not sufficiently support his theory. Combined with even more responses correcting his many misconceptions and claims over the last four years, this one-sided "debate" has been a persistent disruption to the global psoriasis support group. This is an attempt to put the known facts in perspective.
The problem with the theory is that it claims a universal cause and effect from small statistical associations and variations in different populations. Misleading exaggerations have repeatedly been used in an attempt to magnify the true numbers. It has been the basis for sometimes risky treatment recommendations by its proponent, who more often pushes a controversial low-carb diet approach. Reports of psoriasis improvement after dietary modification and associated weight loss are more readily explained by other factors.
Background
Diabetes is a disease characterized by excessive glucose levels. Digestion, especially of carbohydrates and sugars, increases glucose levels, which then decrease as the glucose is metabolized. One of the key elements in glucose regulation is insulin.
There are two classifications of diabetes. When insulin cannot be produced by the pancreas, often because of an autoimmune attack or tumor, this is known as Type I or Insulin Dependent Diabetes Mellitus (IDDM). When available insulin cannot be utilized, this is Type II or Non-Insulin Dependent Diabetes (NIDDM). There are specific risks associated with having diabetes. Since undiagnosed or marginal glucose regulation problems may put one at risk, it is good to be aware of potential problems.
Subclinical NIDDM has gotten a lot of attention because diabetes is reportedly reaching epidemic proportions in western populations, yet may be easily preventable by dietary changes. A hot topic in diet forums is Syndrome X. The definition from the Stanford researchers' website says:
Syndrome X is a cluster of risk factors for heart disease associated with insulin resistance. These risk factors include: hypertriglyceridemia (high blood lipid), low HDL-cholesterol, hyperinsulinemia (high blood insulin), often hyperglycemia (high blood glucose), and hypertension (high blood pressure).
Insulin resistance (IR) is a defect, generally associated with cellular insulin receptors, that prevents proper glucose regulation.
Hyperinsulinism to an emergency room doctor means excessive levels of insulin associated with certain symptoms (weakness, hunger, sweating, staggering, even convulsions or coma), but to a researcher it may simply mean noticably elevated insulin levels.
Insulin resistance can progress to NIDDM. At that point the pancreas cannot produce the amount of insulin required to regulate glucose during digestion. Production of the overloaded pancreas may eventually decline, leading to chronic hyperglycemia. As the condition worsens the pancreas may be exhausted, and excess glucose even generated (by the liver) during fasting between meals, at which point it is likely to be detected during a medical exam.
Genetic factors for insulin receptor defects may be involved with insulin resistance, and it is often associated with obesity. Excess glucose is stored as body fat.
Psoriasis and elevated insulin
There have indeed been several studies that show an association of psoriasis with elevated insulin, and also with the diseases of elevated insulin. This is seen in population studies of diseases that appear with psoriasis.
When the association was first published in the 1950's, the research consensus was that diabetes had no causal relationship with psoriasis. Even if these studies may have used a clinical definition of diabetes more severe than the modern classification, that would be expected to emphasize the lack of a direct connection to psoriasis, since a more extreme condition of elevated insulin and glucose levels would be expected to have more evident side effects. That isn't the case. There is a characteristic array of skin conditions associated with diabetes, but psoriasis is rarely mentioned among them.
A statistical study of skin diseases that appear with diabetes reports that the incidence of psoriasis related to NIDDM is approximately 4.6%, which is only slightly higher than in the general population. Another counterpoint to the IR theory of psoriasis is that NIDDM diabetics suffer most often from skin infections, sometimes uncontrollable (9% in the above study), and they are most serious in the legs and feet. Psoriatics, on the other hand, tend to have fewer skin infections than the general population, most often opportunistic fungi on the lesions.
Since psoriasis is not a disease of extreme insulin resistance, it is unlikely that merely elevated insulin or glucose is the cause. Even if it were so, then psoriasis would be expected to appear in conditions of hyperinsulemia. Elevated insulin appears naturally in some populations, and in at least one common condition.
During normal pregnancy, a state similar to insulin resistance arises as the mother's body metabolism changes to meet the increased demands. This natural state can actually send women who are already at risk for NIDDM into another type of NIDDM known as gestational diabetes. If psoriasis were caused by insulin resistance, it would be expected to worsen during pregnancy. Just the opposite happens. A mother with psoriasis often finds that it improves during pregnancy, and often later flares again after the baby is born. This is more readily explained by her immune system shifting from being suppressed so as not to reject the fetus, to then delivering all the needed antibodies for the newborn baby's undeveloped immune protection.
There are naturally variations in glucose metabolism among different populations. Different enthicities have higher or lower insulin levels, and women reportedly have overall higher levels than men. While these are all natural "set points", the elevated insulin levels are of most concern, because they put that population at greater risk of developing insulin resistance and NIDDM. This is especially true among african, hispanic, native american, and pacific island people. (The highest incidence in the world is among the Pima indian tribe, where over half the adults have diabetes.)
Again, if IR were a major contributing factor in psoriasis, it would be expected to appear more often in populations with elevated insulin levels. Just the opposite is true. Psoriasis is nearly absent in native americans (zero incidence in a study of 26,000 south american indians), and relatively rare among african, hispanic, and asian populations.
The accepted explanation for the variation in both psoriasis and diabetes incidence is the genetic makeup. Psoriasis is a complex disease with multiple genetic factors, and more genes are being discovered as research progresses. Many autoimmune diseases are related to the HLA region on chromosome 6. There are many different markers there that are often used to gauge disease risk and HLA mapping is used to predict rejection/compatabiliy in organ donors. People with active HLA-cw6 region are about 13 times more likely to have psoriasis than the general population. People with HLA-dr3 or HLA-dr4 are at the highest risk for IDDM. NIDDM, however, appears to be another genetically complex disease, with ongoing research in many candidate genes. Like psoriasis, environment also plays a large part in insulin resistance.
It is important to note that population averages do not determine individual variations. Given that about 3% of the general population has psoriasis, over 6% have (diagnosed) diabetes, and that the odds increase with age, it is not at all uncommon for an older adult to have both.
One more notable example of insulin resistance is during treatment with corticosteroids (glucocorticoids) such as prednisone. Steroids are commonly used in treating skin diseases, and they are very effective as short term treatments for psoriasis. Steroid use does carry some risk however, especially with oral use, systemic absorption from injections, or excessive use of potent topicals. Some of the side effects are similar to those of hyperinsulinism, such as rapid weight gain, "moon face", and sweating. Perhaps a more immediate risk is that of a "rebound" effect, where psoriasis flares when the steroids are stopped abruptly, sometimes requiring hospitalization or converting to a more difficult to treat form of pustular psoriasis.
If hyperinsulinism were responsible for psoriasis, inducing it with steroids would not be expected to improve the condition. Nor would a rebound be expected, since insulin metabolism settles back to normal within 48 hours after treatment is stopped. The rebound actually occurs because of a lack of natural cortisol production from the adrenal glands, which have shut down because the body recognizes the synthetic corticosteroids as excess cortisol.
In the late 1970's, a team of italian NIDDM researchers became interested in psoriasis as a risk factor, and conducted at least two clinical studies. They found elevated insulin levels. In their 1977 study, they confirmed indications of insulin resistance fonud in earlier studies, and formed a hypothesis that having psoriasis increases the risk of developing NIDDM (not the other way around). In a later 1979 study, they conducted more detailed measurements, including the counting of insulin receptors in liver cells. They determined that even when obesity is not present, fewer receptors are found on average among psoriatics. They also found a difference in receptor activity between obesity and psoriasis which determined their conclusion:
"Finally, the results we have obtained appear to confirm our first hypothesis, that psoriasis per se is a condition initally responsible for endocrine-metabolic modifications."
Conclusions
The above facts cannot be selectively ignored in an attempt to "prove" a pseudoscientific theory of insulin resistance as a cause for psoriasis. It has been repeatedly debunked from every angle. Until further research uncovers some compelling new basis, the theory needs to be set aside.
Given the various findings of elevated insulin levels among some people with psoriasis, they should be aware that they may be at some risk for developing Type II diabetes. The risk is not great, but at least one study shows it may be double the risk found in the general population. Especially since steroids are overprescribed in the treatment of psoriasis and psoriatic arthritis, patients and doctors should take extra care by watching for symptoms of insulin resistance.
A dietary change that has been recommended for both diabetes and psoriasis is to minimize saturated fat intake, while improving the ratio of "good" fats by increasing the intake of omega-3 oils (abundant in flax seed and in deep sea fish.) The "mediterranean diet" with plenty of fresh fruits and vegetables is often recommended, but "low-carb" evangelists suggest eating more fat and fewer grains.
Many psoriatics who experiment with modifying their normal diet have found that a particular food tends to trigger their psoriasis, but unfortunately these effects are very individualized; What works for one person may do nothing for the next.
-- Ed Anderson
Dave's PsorSite now provides an excellent summary of The Insulin Resistance Risk in Psoriasis
For an excellent consensus report on diabetes risks and research. See this online 275 page book: Diabetes in America, second edition. (requires Adobe Acrobat PDF reader)
The Journal of Clinical Investigation presented a series of perspective articles on insulin resistance. The Full text of the articles are availiable online in both html and Acrobat .pdf format. See the indices for: July 15, August 1, and August 15
The Skin Page hosts all the dermatology research tools used in this report.
Gary Jackson's Rubuttal page was posted in late 2000, last revised August 2001
Created Sept 20, 2000, last updated 9/21, link fix 1/03