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September 24, 2004

Type 2, Weight and Weight Loss

Question from Hewlett, New York, USA:

My daughter has been overweight since she was eight years old. After the last three years of excessive weight gain (more than 20 pounds per year), it has been suggested that my 12 1/2 year old daughter, who is 5 feet, 7 inches, 201 pounds, has pre-diabetes and that we are at the edge. While her yearly checkup showed nothing unusual, due to the weight gain, which was 30 pounds this year, we did a full blood work-up which showed her insulin to be at 49.7. After two appointments with a pediatric endocrinologist and further blood work, fasting, but not a Glucose Tolerance Test, her thyroid and hormones were fine. Their first thought was PCOS (Polycystic Ovary Syndrome), but her glucose was at 5.9 and her testosterone is at 40. In between the two appointments, which was approximately four weeks, my daughter was able to lose four pounds pretty effortlessly. Also, the glucose monitor showed her to be at 5.5. The pediatric endocrinologist was encouraged by that, but is recommending that my daughter start taking Glucophage immediately, along with increased exercise and a careful diet, with a nutritionist. Can she be treated without the medication? She just started eighth grade, and we've seen in the past years that due to school schedules, she tends to gain weight during the school year. Unfortunately, weight loss has always been EXTREMELY difficult and the doctor stated that her Leptin was elevated as well. My husband's family has weight issues. Additionally, my father, as well as my maternal and paternal grandmothers have/had type 2 diabetes. My dad was diagnosed last year, but is no longer on medication. How do we know if there are any options? What are the cons, if any, to starting the Glucophage? I am comfortable with our doctor, who seems to have gotten through to our daughter, which is a big deal. Everything I've seen on the Internet makes it seem that exercise and diet do more for pre-diabetes than medication.


You raise some valid and understandable questions. I will try to answer them, but I will also take the liberty of editorializing a bit.

You are correct: scientific controlled studies have demonstrated that lifestyle changes with diet and increased exercise are more successful than not making changes and are a bit better than metformin (Glucophage) therapy alone. I am not aware of studies that looked at the added benefit of diet/exercise PLUS metformin. (But many, including me, advocate that often.)

Leptin is a hormone produced by fat cells; it should “signal” satiety. While there are rare exceptions, most fat people make more leptin and their bodies tend not to respond to leptin as efficiently: they are leptin resistant. They are also insulin resistant. It seems pretty intuitive to me: if you can lose weight by dieting and exercising more, then there is no need to add pharmalogic therapy.

Glucophage/metformin is a fairly easy medicine with limited side effects. But, it does indeed have side effects, some of which can be extremely serious! As far as I am aware, none of the serious side effects have ever been reported in children: In adults with impaired kidney function, or those with significant liver disease or congestive heart failure, metformin has been associated with a serious condition called lactic acidosis, a situation whereby lactic acid accumulates and can damage the kidney and lead to kidney failure and has been reported to cause death! (Again, this consequence with metformin has not been reported in children.) So, if your obese daughter has normal kidney function and non-serious liver disease, then this should not be a worry. There are reports in adults on metformin who receive iodine x-ray contrast dye that the lactic acidosis can be precipitated. I forewarn my families that they should wear medical identification that the child is on metformin and is at risk of lactic acidosis (this is to forewarn emergency crews should the child be in an accident and require special iodine x-rays, e.g.IVP, arthogram, CAT scan, etc.) If there is an elective x-ray requiring iodine dye, then it can be done after the patient has stopped the metformin for about four days. Metformin can interfere with Vitamin B12 levels and many suggest taking a B12 or multivitamin supplement when taking metformin.

Some obese patients have fat deposits in the liver This is called “non-alcoholic steatohepatitis” which is often abbreviated as NASH. Metformin is the drug of choice for NASH. Metformin does blunt appetite a bit. Commonly, a transient side effect of metformin is some intestinal irritation associated with nausea or diarrhea, which usually is temporary.

Metformin is commonly used for people with type 2 diabetes, but is now very commonly used for people at high-risk or “pre-diabetes.” Some consider it the first line against polycystic ovary disease (PCOS). All of these conditions have in common an underlying resistance to the effect of insulin. Metformin decreases the liver’s glucose manufacturing output; if you make less glucose you do not need as much insulin. But, if you do not follow a low sugar diet, then I think you’re pretty much wasting time.

So…..diet can work without metformin; metformin does not work well without diet.

I am confused about the glucose levels you report above. 5.5 and 5.9: are these SI (International System) units? In New York? So, I will assume they correlate to 99 to 106 mg/dl. Maybe you are giving her hemoglobin A1c values and these were 5.5% and 5.9% ? An insulin level of 49.7 uU/mL, fasting, is elevated and demonstrates insulin resistance. It would be nice to know what the simultaneous fasting glucose level was.

So, I think that, in an otherwise healthy 12 year old, there are many advantages of metformin. While there are risks, they are low, especially in a child.

And, now, the editorial: Your 12 1/2 year old daughter is 5 feet, 7 inches and 201 pounds. This provides a body mass index (BMI) of 31.6. A BMI of more than 30 defines obesity in an adult and your daughter is not yet 13! You describe 20 plus pounds a year for more than four years and, in the past year, it was 30 pounds. This weight gain did not occur in a vacuum. I must presume that you all recognized this and were worried and presumably at least tried some sort of maneuvers surrounding diet to try to minimize this, but without success. Why would you think now, when she is near more than 50 pounds overweight, relative to her height, that diet alone, or with exercise, will suddenly be successful? By all means, try diet and exercise now, if she has not really done that. Be sure she avoids “simple sugars” and cuts back on complex starchy foods. If she is successful, great. Otherwise, look to metformin for some additional help while maintaining that diet. I think a testosterone level of 40 ng/dL in a 12 year old girl is generous and does not exclude PCOS.

Finally, long term effects of obesity include increase risk of breast cancer, colon cancer, heart disease, and others. The obesity fight for her will likely be life-long.