Acanthosis nigricans
There’s strong evidence of a causal role for chronic hyperinsulinemia in acanthosis nigricans (AN). The authors of one paper noted that AN could even be considered as a clinical surrogate for laboratory-documented hyperinsulinemia. AN is more common in people who are overweight or obese, but it’s not exclusive to these patients. (Insulin resistance occurs across the spectrum of body weight, including in those at a “normal” BMI.)
How does elevated insulin affect the skin this way? According to one paper, “The endocrine origin of this condition is beyond doubt. Insulin and insulin-like growth factor-1, and their receptors on keratinocytes are obviously involved in the complex regulations leading to the peculiar epidermal hyperplasia.” Constant exposure to high levels of insulin causes keratinocytes or dermal fibroblasts to grow or proliferate. This seems to be the primary mechanism: “Elevated insulin concentrations result in direct and indirect activation of IGF-1 receptors on keratinocytes and fibroblasts, leading to proliferation.”
Acanthosis nigricans doesn’t affect only adults. Younger people may be afflicted as well. One study’s authors proposed that all children and adolescents with AN should be evaluated for insulin resistance regardless of BMI. In this study, all subjects with AN had elevated fasting insulin but normal glucose. Average fasting glucose was in the high 80s (mg/dL) but insulin was at the high end of the normal range: among those with AN, mean fasting insulin was 15.6, 18.8, and 27.6 µIU/mL in subjects who were at a normal weight, overweight, or obese, respectively. (Some labs use reference ranges for fasting insulin that go as high as 20 or 24 µIU/mL, but an optimal level may be below 10 µIU/mL.) This cannot be emphasized enough: even when fasting glucose and BMI are “normal,” this does not rule out the presence of hyperinsulinemia.
The metabolic origins of AN have been known for at least thirty years. A paper from 1992 noted that “acanthosis nigricans is an easily detected empirical marker for elevated risk of type II diabetes. The lesion can appear long before the onset of glucose intolerance. Thus, including acanthosis nigricans screening in a comprehensive disease-prevention program can help identify people at risk for type II diabetes prior to the actual onset of glucose intolerance, as well as individuals with undiagnosed diabetes.” People should not have to wait until they have prediabetes or type 2 diabetes to be told they have serious metabolic dysfunction brewing when something immediately visible on their skin can tip them off much earlier—and perhaps prompt them to make lifestyle changes to reverse this.
Acne
Conventional thinking says that eating greasy foods equals a greasy face. It’s commonly believed that acne comes from poor hygiene, or from indulging in things like pizza, potato chips and french fries. But what if excess consumption of carbohydrates—not fats—is the real culprit?
In a study of women with acne, compared to women without acne, those affected were found to have higher levels of fasting insulin, fasting glucose, HOMA-IR, and area under the curve (AUC) for glucose and insulin measured during an oral glucose tolerance test. Hyperinsulinemia may contribute to acne in men, too. In a study of young men, subjects with acne had double the prevalence of insulin resistance compared to those without acne (22% versus 11%, based on HOMA-IR). The prevalence of metabolic syndrome was also double: 17% versus 9%. A different study in young men showed that compared to men without acne, men with it had higher blood pressure, higher BMI, lower HDL-cholesterol, larger waist circumference, higher HOMA-IR, higher fasting insulin and glucose, and higher insulin & glucose during an OGTT.
Potential mechanisms by which elevated insulin contributes to acne were proposed almost twenty years ago. They may be related to insulin-induced increases in IGF-1 and reductions in binding proteins, which may in turn affect functioning of the body’s natural retinoids. Additionally, elevated androgens (as seen in PCOS) may stimulate increased sebum production, a necessary step in the development of acne. (Increased serum levels of IGF-1 have been observed in adult women and men with acne even in the absence of higher androgens, though.)
Other skin conditions
Psoriasis and hidradenitis suppurativa are additional conditions that may be consequences of metabolic syndrome or insulin resistance. The latter issues are common findings among children and adults with psoriasis. Even in those who are not formally diagnosed with metabolic syndrome, insulin resistance should be suspected in those with severe psoriasis. One paper notes that “progressive adiposity and resultant metabolic syndrome are but the beginning steps in the ‘psoriatic march.”
Turning to hidradenitis suppurativa (HS), the Mayo Clinic notes that HS is associated with diabetes and metabolic syndrome and is more severe in people who are overweight. Compared to age- and sex-matched controls, HS patients have higher rates of type 2 diabetes, PCOS, dyslipidemia, hypertension, obesity, fatty liver, and other issues we would expect in people with chronic hyperinsulinemia. According to one paper, “Metabolic disorders including obesity and metabolic syndrome are the most common associated conditions observed in patients with hidradenitis suppurativa.” On the surface, it’s understandable that HS occurs in those who are overweight, as skin rubbing together more than usual could result in the broken skin, pustules and other signs of HS, but this does not explain HS in patients who are not overweight. So, perhaps elevated insulin and the resulting changes to the skin itself is a contributing factor even in people at a normal weight.
Diabetes Drugs for Skin Conditions
Considering the undeniable role of hyperinsulinemia in a host of skin issues, it’s not surprising that metformin is becoming commonplace in dermatology. Metformin and rosiglitazone have been studied in patients with acne, acanthosis nigricans, hidradenitis suppurativa and more. In a study of men with acne resistant to common treatments, compared to subjects using a conventional anti-acne cream, subjects who used the cream and followed a low-glycemic diet (also considered low-calorie, at 1500-2000 kcal/day) plus metformin for 6 months, subjects in the diet plus metformin group had much greater improvement in skin appearance.
In a study of metformin in patients with hidradenitis suppurativa, 75% of subjects were found to have insulin resistance. Metformin therapy led to improvements in 68 percent of subjects, including some who experienced “quiescent disease”—a remission or period of inactivity.
While medications may be helpful, if insulin resistance or metabolic syndrome are primary contributors to these skin conditions, it may be more effective for the long term to target that underlying metabolic dysfunction more directly, such as with a very low-carb diet.