Narrowing Down The Main Cause Behind Insulin Resistance

DEAR DR. ROACH: What is the main cause for insulin resistance? I was diagnosed with Type 2 diabetes about five years ago. I've maintained a consistent weight under 200 pounds, and I'm only 5 feet, 9 inches tall. I was able to get my A1C level to 7.2% last summer, but in late fall, my numbers started spiking, even with insulin. I now find myself injecting crazy amounts of insulin just to maintain normal glucose levels.

I'm on a diet of 40 grams of carbohydrates a day. I walk close to 20,000 steps a day. But on a regular day, I a inject 30-40 units of mealtime insulin before a low-carb, high-protein meal. Still, my level spikes above 250 mg/dL, and it stays there for a few hours. -- A.R.N.

ANSWER: Insulin is a signal that there is plenty of sugar in the body, and the body uses insulin to take sugar out of the blood and into cells. Normally, just a little insulin will make blood sugar levels go down a lot. When it takes a lot of insulin to lower a blood sugar level, we say that there is insulin resistance. A great deal of work has been done trying to elicit why people develop resistance to insulin.

There are some rare congenital cases, involving mutations of the insulin receptor. There are also rarely acquired immune-mediated causes that have antibodies to insulin or the insulin receptor and have an extremely high resistance to insulin.

However, most cases of insulin resistance are associated with obesity. Your BMI is 29.5, suggesting that you're overweight but not obese. In this case, abdominal fat is more metabolically important, since it can lead to free fatty acids and compounds called adipocytokines, which may contribute to insulin resistance.

People with abdominal obesity and insulin resistance often have abnormal cholesterol levels and high blood pressures, a combination called "metabolic syndrome." Blood pressure and cholesterol must often be treated independently.

Insulin works to lower blood sugar, but there are four main hormones that oppose insulin to raise blood sugar: cortisol, catecholamines, glucagon and growth hormone. Elevated levels of any of these will cause insulin resistance. I know this isn't your case, but the pregnancy hormone human placental lactogen causes insulin resistance and is the proximate cause for gestational diabetes.

Some medicines (steroids, birth control pills and HIV medicines) can cause insulin resistance. Critically, glucose itself can cause insulin resistance! High blood sugar levels prevent insulin release as well. That's why getting and keeping a normal blood sugar level is so critically important, especially when a person is first diagnosed.

Management of a person with high amounts of insulin resistance can be challenging. You are already doing amazingly well with exercise, and it sounds as though your diet is of the type that is commonly recommended. Medications that reduce insulin levels -- such as metformin, GLP-1 agonists and thiazolidinediones -- are often recommended to reduce the amount of insulin used.

Your situation is not common, and you should absolutely be in the hands of an endocrinologist who specializes in diabetes.

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Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth@med.cornell.edu or send mail to 628 Virginia Dr., Orlando, FL 32803.