Research & Education

The Underappreciated Role of Elevated Insulin in Skin Disorders

For patients living with acne, skin tags, psoriasis and other visible skin disturbances, these issues can severely diminish self-esteem and quality of life. But these things are far more than skin deep. A staggering amount of research indicates they are the surface manifestations of damaging hormonal imbalances on the inside—imbalances that could eventually result in type 2 diabetes, cardiovascular disease and other long-term consequences of chronically elevated insulin, a.k.a. metabolic syndrome. 

Most of us are accustomed to thinking that greasy foods equal a greasy face, and we assume that acne, especially in teenagers, comes from indulging in pizza, potato chips and french fries. But what about other skin conditions that we don’t associate with these foods—things like hidradenitis suppurativa and increased pigmentation? Chronic hyperinsulinemia is a driving factor in a host of other conditions not typically associated with insulin, such as gout, migraines, erectile dysfunction and enlarged prostate, so it shouldn’t surprise us that insulin could be the culprit with certain skin disorders as well.

Before looking more closely at some of the research supporting this idea, it must be clarified that while insulin resistance (IR) is typically associated with overweight, obesity and type 2 diabetes (T2D), chronic hyperinsulinemia can and does occur in people of “normal” body weight and who are not diabetic. Consider the fact that neither body weight, nor BMI, nor even body fat percentage, are part of the official diagnostic criteria for metabolic syndrome. Fasting glucose is a criterion, but the diagnosis can be made with just three of the criteria (such as elevated blood pressure, high triglycerides and low HDL), so one need not have elevated fasting glucose to be living with metabolic syndrome. Many of the sequelae from T2D (retinopathy, nephropathy, vascular disease) are thought of as consequences of chronic hyperglycemia, but there is a massive epidemic of patients with normal blood glucose but chronically high insulin, and the elevated insulin, even in the absence of elevated glucose, drives a number of chronic non-communicable illnesses. This is a massively underrecognized problem that underlies numerous conditions not typically associated with insulin at all.


Insulin and the Skin

It’s under-recognized among medical professionals—and even more so among patients—that a wide array of skin issues are caused or exacerbated by chronic hyperinsulinemia. The list includes but may not be limited to acne, skin tags, acanthosis nigricans, psoriasis, cellulitis, and hidradenitis suppurativa. One paper referred to these as “cutaneous manifestations of obesity and the associated metabolic syndrome,” but what about patients with these skin issues who are not obese? Again, hyperinsulinemia is not a condition exclusive to individuals who are overweight or obese. Metabolic syndrome should not be ruled out in patients at what would be considered a “healthy” body weight who present with one or more of these skin issues.  

The influence of insulin on the various hormonal abnormalities in PCOS is well known (e.g., elevated testosterone, reduced sex hormone binding globulin and an elevated ratio of luteinizing hormone to follicle stimulating hormone), and PCOS brings with it several skin manifestations such as oily skin, acne, and hirsutism, so there’s good reason to believe chronic hyperinsulinemia may be driving other skin issues as well.

Acrochordons (a.k.a. skin tags) are an interesting thing to explore with regard to the role of insulin. While perhaps aesthetically unpleasing, these are usually considered benign in terms of a medical problem. However, research indicates these are anything but benign. Study authors have described skin tags as “a cutaneous marker for impaired carbohydrate metabolism,” and others have noted the same thing, saying that skin tags are “a cutaneous sign of impaired carbohydrate metabolism, hyperlipidemia, liver enzyme abnormalities and hypertension” – all issues that cluster with insulin resistance.

In a case-control study of subjects with two or more skin tags and age- and gender-matched controls, compared to controls, subjects with skin tags had significantly higher mean levels of fasting glucose, triglycerides, and liver enzymes (ALT, AST, GGT and alkaline phosphatase), along with higher blood pressure and lower HDL, all indicative of metabolic disturbances tied to chronic hyperinsulinemia.

In a separate case-control study comparing subjects with at least three skin tags to controls matched for age, sex and BMI, subjects with skin tags had a higher frequency of T2D (23% among cases versus 8.5% for controls). There was a positive correlation between the total number of skin tags and mean fasting plasma glucose, leading the study authors to write, “With regard to the importance of early diagnosis of diabetes, we recommend a high level of suspicion for impaired carbohydrate metabolism in patients with skin tag.” No correlation was found between the number of skin tags and BMI. Again, it’s not about body weight; it’s about insulin levels, and in some individuals perhaps glucose as well.

These are not isolated findings. Another case-control study compared three groups of subjects with multiple skin tags (30 normal BMI, 30 overweight and 30 obese individuals) to healthy controls matched for age, sex and BMI. HOMA-IR was significantly higher in all groups of skin tag patients compared to BMI-matched controls, with 71% of cases meeting the criteria for metabolic syndrome. Yet again we see that body weight is not the driving factor in development of skin tags, because individuals at the same BMI do not show equal development of skin tags.

It should be noted, though, that among the skin tag patients, higher BMI was correlated to increased number and greater extent of skin tags. This finding was echoed in a later study of nondiabetic subjects who were overweight or obese and had acanthosis nigricans (97% of subjects), keratosis pilaris (42%), skin tags (77%), and plantar hyperkeratosis (38%). The degree of obesity was significantly associated with acanthosis nigricans, skin tags and plantar hyperkeratosis, while number of skin tags, acanthosis nigricans distribution and neck severity score were significantly and independently associated with insulin levels. These subjects were nondiabetic; here again we see it’s not the glucose; it’s the insulin.


Metformin for Skin Conditions and Future Treatment Outlook

The fact that so much research has been done studying the effects of metformin on difficult-to-treat dermatological conditions—and that so much of it is so promising—indicates that there clearly is a connection between these issues and insulin and/or blood glucose. This diabetes drug has been studied with encouraging results in patients with acne, skin tags, acanthosis nigricans, eruptive xanthomas, hidradenitis suppurativa and more.

These findings suggest that dermatologists may be in a unique position to identify chronic hyperinsulinemia in its early stages, long before it progresses to metabolic syndrome, type 2 diabetes or cardiovascular disease. One paper states this in no uncertain terms: “Being aware of such clinical signs and the underlying systemic disorders may facilitate earlier diagnoses, thereby permitting earlier of therapy initiation and prevention of long-term sequelae. In this process, dermatologists are key figures in the early detection of MetS and its clinical manifestations.” 

If these cutaneous issues are early warning signs of IR, doctors can inform their patients that elevated insulin is driving their skin issues and that there’s something they can do about it, such as adopting a low-carb or ketogenic diet. Just as erectile dysfunction of otherwise unknown origin may be the first clinical sign of metabolic disease, these skin problems can be the canary in the coalmine indicating pathological processes going on internally, particularly in those with few other biomarkers that would indicate this metabolic situation.

Perhaps fasting insulin and HOMA-IR testing should be added to the dermatologist’s toolkit. There’s an endless array of creams and ointments, laser therapies and light treatments, but perhaps patients might be better helped not by what they put on their skin, but by addressing what’s happening internally, inside and underneath the skin. Visible manifestations of underlying hormonal imbalances can’t be permanently corrected by topical application of medicinal products. The root cause must be addressed: if the driving factor is a hormone imbalance, then the hormone imbalance needs to be corrected. Dietary and lifestyle changes are instrumental here, including supplementation with compounds known to improve carbohydrate metabolism and glucose and insulin dynamics, such as chromium, berberine, alpha-lipoic acid and inositol.