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In the battle to loose weight, I seem to be loosing

I never think of myself as fat. The neck sizes of my shirts are bigger than they used to be, and my middle more rounded, but I comfortably accept this larger me. In my mind, any excess weight is temporary. Like most Americans, I confidently look forward to shedding the extra weight when I get around to it, as if it were a coat I could take off.

Thus it came as something of a shock this spring when my annual checkup revealed that I was slipping into Type II (late-onset) diabetes. My blood sugar was 140, well above the threshold for diabetes. While the high level might reflect a recent rich meal, there was a more certain indicator. Sugar in the blood tends to attach itself to the hemoglobin in red blood cells. The process is slow. It takes months of high blood glucose levels before glucosylated hemoglobin is elevated above the diabetes threshold of 6. My reading was 7.

One in twenty Americans suffer from Type II diabetes, the inability to use insulin efficiently to regulate blood sugar. Untreated, Type II diabetes is a major cause of blindness, kidney disease, amputations, and death. This is not a club I want to be a member of.

80% of Type II diabetics are overweight. Why does excess weight lead to Type II diabetes? Scientists aren’t really sure, but recent work in mice suggests that fat might contribute to Type II diabetes by way of a hormone called resistin that is produced by fat cells. The hormone prompts cells to resist insulin, so that they cannot process blood sugar efficiently. This appears to be the link between fat and Type II diabetes: Excess fat cells produce added resistin, which elevates blood glucose.

This suggests that Type II diabetes might be treatable with drugs that inhibit the resistin hormone. A new class of anti-diabetic drugs called thiazolidinediones, or TZDs, seem to block resistin in mice. In TZD-treated obese mice, insulin is free to do its job, and blood sugar levels drop to normal. However, TZDs also have other effects. A drug targeted specifically at the resistin gene, preventing it from “turning on,” would be just the ticket. A lot of researchers will be looking for it.

In the meantime, it looks like its time for me to loose weight.

The Centers for Disease Control and Prevention reported at the end of last year that 61% of US adults are overweight. Specifically, 35% of adults are moderately overweight and have a body-mass index between 25 and 29.9, and 26% more are obese and have a body-mass index of 30 or higher.

Are you overweight? To calculate your body-mass index, first multiply your weight in pounds by 703, and then divide by your height in inches, squared. For example, I am 6’ 0” tall (that’s 72 inches) and today weigh 189 pounds. My body-mass index is thus [189 X 703] / [72 X 72] = 25.6.

My current 189 pound weight hasn’t come easy. Exercising, and eating a lot less than I want to, I have over four months painfully reduced my weight from mid-winter’s 205 pounds. I have little doubt that my mid-winter body-mass index of 28 was a major factor contributing to my developing Type II diabetes.

I have no idea wether or not I will be able to keep my weight this low. Eating less hasn’t been much fun. A person can loose weight on any diet that limits calories to 1,400 to 1,500 a day, but 1,500 calories a day isn’t exactly a feast. What I would really like is to be able to eat more and weigh less -- all pleasure, no pain.

Imagine my delight when reading in the journal SCIENCE last month of research that could in principle make my fantasy a reality.

In order to make fat, your body first converts foodstuffs (carbohydrates, fats, and proteins) into small energy-rich molecules called acetyl CoA. It then stitches these acetyl CoA molecules together to form the long chains that are fat molecules. The enzyme that catalyzes the first key step is called acetyl CoA carboxylase, or ACC.

Researchers at Baylor College of Medicine in Houston created genetically engineered mice that lacked one or the other of two forms of the enzyme. The mice without ACC1 all died as embryos. But the mice that lacked ACC2 did just fine, growing and reproducing normally and staying in good health. But while the mice lacking ACC2 ate more than normal mice, they weighed less and accumulated less fat. As adults, they had 50% less body fat than normal mice.

So what I want is a drug that inhibits ACC2 in the human body. And I have no doubt the pharmaceutical companies are looking for one. Imagine the potential sales of such a couch potato diet pill! I remind myself that a mouse is not a human, and there is no guarantee an ACC2 inhibitor would work to safely reduce a human’s weight. But wouldn’t it be wonderful?

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