Insulin Resistance: Potential Treatment?

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It's widely recognized nowadays that many people have a condition known as insulin resistance. Internally, their cells have become desensitized to insulin, which ultimately forces the body to create more of it in order to meet the cellular demands on the body (insulin is required to move glucose into the cells for usage). Unfortunately though, high insulin levels lead to heart disease, type II diabetes, obesity (or a difficulty in losing weight), high blood pressure, and are potentially implicated in several cancers, including breast.

This metabolic condition is known in the literature as "metabolic syndrome" or "syndrome x", but unfortunately nobody has been able to determine a cause or a successful treatment for it. Exercise tends to re-sensitize muscle cells to insulin, but only temporarily. Reducing carbohydrates naturally reduces insulin levels, which helps most people lose weight and reduce the symptoms of hyperinsulinemia (chronically high levels of insulin in the blood). But these are treatments, and not cures. They simply reduce the symptoms of the problem, leaving the actual metabolic disturbance in place.

What's interesting is that if you analyze populations that are inherently obese and diabetic (one such population are the Pima Indians in the United States), what you'll usually find is that paradoxically they are malnourished. That is, instead of excess calories and an overabundance of food, you see the opposite. Most of these populations sustain themselves on meager rations of rice and beans.

As is normal on some evenings, I did a quick scan of the medical research last night to see if there were any new developments in this area. Normally I get an email blast with them all on Sunday nights, but last night I went searching for items I don't normally have on my email list. That's when I discovered a whole thread of research regarding use of the antioxidant Alpha Lipoic Acid.

The body makes use of many antioxidants, primarily vitamin C, melatonin, and vitamin E. The purpose of antioxidants is to deactivate molecules known as free radicals. Free radicals are the byproducts of various chemical reactions in the body, and are biologically active since they have a free electron available. If not deactivated by an antioxidant, they will eventually react with something they weren't meant to, often forming what are called advanced glycosylation end-products (AGEs), which are implicated in aging.

It turns out that not only is alpha lipoic acid (ALA) a strong antioxidant, it can also recharge various other antioxidants, including vitamin E and coenzyme Q-10. In addition, it seems to have a direct affect on the insulin pathway, allowing insulin to be used more effectively in cells. In fact, insulin resistant rats (which mimic very closely insulin resistant humans) lost "a profound amount of weight" on only four weeks of ALA treatment.

A group of patients who had gained weight on antipsychotic drug's were put on a treatment of ALA. After 12 weeks, there was a significant reduction in body weight and a decrease in cholesterol:

The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080).

Another study I read set about to see what changes in insulin sensitivity would occur after oral administration of ALA. After four weeks, insulin sensitivity shot up from 3.2 to 5.9, simply by taking an oral antioxidant for four weeks.

At the end of the treatment period, [insulin sensitivity] of diabetic patients was significantly increased: M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min (mean+/-sD), p<0.01; and [insulin sensitivity index] from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 (mean+/-sD), p<0.05.

Normally when I read studies like this, I find just as many studies that refute the claim as I do to support the claim. Last night though I found about 10 studies like this, all of which said the same thing -- ALA increases insulin sensitivity, often bringing it inline with the control subjects, and none that refute it at all.

Given that insulin resistance might potentially be countered by an antioxidant such as ALA, ultimately this might mean that insulin resistance (and logically, type II diabetes) is most likely a side affect of internal oxidative stress. This actually would reconcile the paradox in populations where obese subjects are often malnourished, since malnourishment would lead to a decreased state of internal antioxidants, and make oxidative stress more likely. Just a hypothesis obviously, but one that jives with the current observations.

Anyways, it's the first exciting research on the subject I've read in years, so I wanted to share it.