Early Insulin Resistance Predicts Subsequent Risk of Metabolic Syndrome

Insulin resistance and metabolic syndrome are most often thought of in connection with middle age. However, an article in the March 2009 issue of the journal Metabolism shows that these conditions get their start early in life.

A biracial group of 475 girls was studied first at ages 9-10 years and then at ages 18-19 years. In the first stage of the study, the invesigators determined the body mass index (BMI) of each girl. They also determined a score called the HOMA-IR, or homeostatis model assessment of insulin resistance. Insulin resistance can be measured using an oral glucose tolerance test (OGTT), but this requires several hours and numerous blood draws. In the HOMA-IR, the fasting levels of insulin and glucose are determined, multiplied, and converted into a score that correlates well with the insulin resistance determined by more technically-demanding methods. The girls were divided in two ways: (1) according to whether their BMI put them in the bottom, middle or top third of the group with regard to to relative obesity (2) according to whether their HOMA-IR score put them in the bottom, middle or top third with regard to relative insulin resistance.

Nine years later the girls were assessed for five metabolic syndrome risk factors. These included:

• Triglycerides
• High-density lipoprotein cholesterol
• Systolic/diastolic blood pressure
• Waist circumference
• Blood glucose

Each risk factor measurement was converted to a z score, which is a way of expressing the relationship of a specific measurement to the population average and the standard deviation of that particular variable. The five z scores were added for each individual. If the total z score was negative, that meant that the individual had a lower risk of metabolic syndrome. (The more negative the total, the better in this instance.) If the total z score was positive, that meant that the individual had a higher risk of metabolic syndrome.

The results were not surprising. The girls who had the lowest BMI and the lowest insulin resistance at ages 9-10 were found to have the lowest risk of metabolic syndrome at ages 18-19. As initial BMI and insulin resistance scores rose, the subsequent scores for risk of metabolic syndrome also rose. The girls who had the highest BMI and the highest insulin resistance at ages 9-10 had the highest risk of metabolic syndrome at ages 18-19. It appears that childhood obesity and insulin resistance interact to produce a higher risk of metabolic syndrome in early adulthood.

Taking it one step farther, the significance of metabolic syndrome in childhood was underlined by a study recently published in the journal Pediatrics, Metabolic Syndrome in Childhood Predicts Adult Cardiovascular Disease 25 Years Later. In this study, the investigators found that the incidence of cardiovascular disease for their 31 patients with pediatric metabolic syndrome was 19.4%, while the incidence was 1.5% for the subjects without metabolic syndrome as children. If these findings are correct, children with metabolic syndrome are significantly more likely than their peers to experience cardiovascular disease twenty five years later as adults.

The obvious question becomes, what happens to these children if intervention takes place between their pre-teen years and their forties? And what would that intervention be? Would it be pharmacological? Would it involve a change in dietary habits? There is a bias at this blog for at least trying a low-carb eating strategy to lower BMI, reduce insulin resistance, avert childhood metabolic syndrome and prevent the progression to adult cardiovascular disease. Whether or not that approach will be tested in the scientific community remains to be seen.

Reversal of Type 2 Diabetes?

Unfortunately there is still no cure for type 2 diabetes. But a recent study published by Eric Westman's group at Duke University suggests that a diet with less than 20 grams of carbohydrate per day or a low-calorie/low-glycemic index diet could enable some type 2 diabetics to decrease their medication and lower their hemoglobin A1c levels.

Investigators randomized 84 obese type 2 diabetic subjects into a Low-Carb group or a Low-Calorie/Low-Glycemic Index (Low Calorie/Low-GI) group. (Full disclosure: the study was funded by the Robert C. Atkins Foundation.) For a period of 24 weeks the Low-Carb group was instructed to eat an Atkins induction-level diet (less than 20 grams of carbohydrate per day, without caloric restrictions). During the same time the Low Calorie/Low-GI group was instructed to eat a reduced-calorie diet that contained 55% low-glycemic index carbohydrates. In the Low-Calorie/Low-GI group, the target caloric intake was set for each individual to provide 500 calories less than that required for weight maintenance.

Fifty eight percent of the enrollees completed the study. Prior to the study the average food intake was 2128 calories a day, with 245 grams in the form of carbohydrates. During the study, the Low-Carb completers ate a daily average of 1550 calories with 49 grams (13%) of the total coming from carbohydrate. The Low-Calorie/Low-GI completers averaged 1335 calories per day with 149 grams (45%) coming from carbohydrate. While compliance with protocol design was not perfect, the Low-Carb group ate about 16% more calories and about two-thirds fewer carbs than the Low-Calorie/Low-GI group did.

Over the 24 weeks of the study, the Low-Carb group lost an average of 24.4 pounds and the Low-Calorie/Low-GI group lost an average of 15.2 pounds. At the same time, both groups saw significant improvements in fasting glucose, fasting insulin and hemoglobin A1c. It is commonly believed that for type 2 diabetics, weight loss causes a drop in hemoglobin A1c. Interestingly, in this group of subjects there was no correlation at all between the amount of weight loss and the level of hemoglobin A1c. (The corresponding figure can be found here.)

Of the 50 patients who were taking insulin at the start of the study, eight in the Low-Carb group and three in the Low-Calorie/Low-GI group were able to decrease or discontinue their insulin altogether. (Click here for a tabular summary.)

The authors go to some lengths to show that the Low-Carb diet was superior to the Low-Calorie/Low-GI diet in this study. In any case, it appears that type 2 diabetics who are able to adhere to either of these diets in the long term can see a significant improvement in their symptoms and a decrease in the need for injected insulin.

Health Care Sacrifices

Heart disease is increasing in the United States. According to the following graph, hospital discharges for coronary heart disease went from about 1.4 million per year in 1970 to about 2.1 million per year in 2000.

In spite of the increasing incidence of heart disease, the death rate from heart disease is decreasing. According to the figure below, from the New York Times, the one-year heart attack survival rate in Medicare patients went from about 58% in 1986 to just under 70% in 2000. The second graph suggests the reason for this: Medicaid hospital spending doubled during that time period.

Patient survival is good. Increasing Medicare costs is bad. Some people have proposed limits on medical spending as a way to cope with the increased costs. One of these is Tom Daschle, who was recently nominated to be head of the Health and Human Services Department. Mr. Daschle's sudden withdrawal from that nomination was unexpected, and he had already provided much advice about acting quickly to ensure that health care legislation could be enacted without the debate and delay that had caused the 1994 health care overhaul to be abandoned.

In 2008 Mr. Daschle wrote a book called Critical: What We Can Do About the Health-Care Crisis. In it he advocated many of the provisions that have found their way into the 2009 economic stimulus package. These include moving medical record keeping to an electronic format that will be available to a new federal bureaucracy, the National Coordinator of Health Information Technology. This organization has a mandate to reduce costs and "help guide medical decisions at the time and place of care."

Mr. Daschle also recommended the creation of another bureaucracy to be modeled the after United Kingdom's National Institute for Clinical Excellence (NICE). This entity is found in the stimulus package as the Federal Coordinating Council for Comparative Effectiveness Research. It is described in the draft report for the bill as being expected to apply a cost-effectiveness standard to approve or reject treatments using a formula that divides the approximate cost for a treatment by the years the patient is expected to benefit from that treatment. The Council will enforce the standard by evaluating doctors and hospitals based on whether or not they are "meaningful users" of the new system. Translation: as Americans get older, they should expect to receive less medical care.

It is hard to contemplate health care reform built on the principle of denial of care to the elderly. However, Mr. Daschle has said that health care reform will not be pain free. He believes that Americans should be more like Europeans in their ability to accept hopeless diagnoses, to do without experimental treatments and to refrain from expecting too much from the health care system. It may be necessary in such a system to provide health care benefits for younger citizens and then ask citizens to be willing to sacrifice those benefits in their later years.

One hopes that all of this has very little to do with low-carbing. It is still permissible to buy eggs, cheese, meat and fresh vegetables. It is still permissible to avoid refined carbohydrates. As far as the health care system, following a low-carb lifestyle will prevent or lessen the impact of many medical conditions including diabetes, heart disease, gallstones, and dental cavities. And being able to achieve excellent health without resorting to medication and hospitalization is a good thing.

If I'm so fat, why am I always hungry?

Body fat serves a number of purposes. It cushions our organs, it insulates us, and it provides a way to store energy. A normal amount of body fat is about 10-20% for men and 15-25% for women. So far, so good.

But sometimes we get too fat. What then? It seems logical to expect that our appetites would decrease, the extra fat would be burned as energy, and we would return to a normal fat percentage once again. But as millions of overweight people can testify, that is not how it always works. They can eat a meal, leave the table feeling full, and two hours later they will be ravenously hungry. They look down at their rolls of excess body fat and wonder, "Why in the world am I hungry? Why can't I just use some of this fat instead of having to eat again?"

In most cases, the answer is one word. Insulin.

Insulin is a hormone which is secreted by the pancreas whenever we eat carbohydrates or protein. Insulin sends a message to the tissues of the body--store nutrients! It is not practical for us to eat continuously. So we eat discrete meals, use some of that energy immediately, and (in response to the signal from insulin) store the rest for use later. Several hours after a meal is consumed, our insulin levels will normally fall, and this will permit nutrients to come back out of storage until it is time for our next meal.

As people get older, the insulin response system may begin to break down. The pancreas has to secrete more and more insulin in order to store nutrients following a meal. The elevated insulin takes longer and longer to return to normal levels, until it stays somewhat elevated all the time. As insulin levels stay high, it becomes progressively harder for stored nutrients to be released between meals. In other words, energy (mostly in the form of fat) is being stored at mealtime, but the energy in the fat can no longer be released efficiently between meals. The result? If a person has excess fat stores but also has persistently high insulin levels, he will be less and less able to access the energy he has stored, but will be forced to eat frequently to provide his body with the energy it needs. Even though he is fat, because of elevated insulin, he will find that he is always (or almost always) hungry.

Obviously the next question is, if a fat person wants to overcome constant hunger, how does he address his elevated insulin? This post, Reversing Insulin Resistance, shows that simply eating a low-carbohydrate diet significantly reduced insulin levels in a small group of obese type 2 diabetic patients. For a more detailed answer, please see this post. It summarizes the three primary strategies for lowering insulin (eat low-carb, eat moderate protein and wait 5-6 hours between meals) and gives several more suggestions for bringing insulin levels (and hunger signals) back into a normal range.