The Doctor Explains

Metabolic Syndrome Or Insulin Resistance Syndrome

So I (or my child) has insulin resistance syndrome, is that bad?
Sometimes also called the “metabolic syndrome” or syndrome X, you are but one member of a global epidemic of insulin resistance syndrome that is fast spreading through Western  countries, and much of the non-Western world as well. While most persons affected by insulin resistance syndrome (IRS) are overweight and many highly obese persons have insulin resistance, persons who are not over-weight can become insulin resistant too. In children, insulin resistance can precede excessive weight gains.

 Certain ethnic groups are more prone to IRS than others because of their genes and ethnicity related life-styles.  Some 30% of adults in the US are medically obese with a similar number overweight. Whereas the basic predisposition appears to be strongly genetic, environmental factors notably an “unhealthy-high carb-high animal fat” diet and lack of exercise are also keys to its development. The bad news about IRS is that it may result in a number of bodily problems (lipid problems, high blood pressure, kidney disease, fatty liver disease, sex hormone imbalance and type-2 diabetes) that may culminate in widespread blood vessel disease (atherosclerosis).

The good news is that with commitment to changes in life style and effective medications, the condition can be controlled, preventing specific long term problems such as infertility, polycystic ovaries, heart disease, stroke and peripheral vascular disease of the legs and feet. Good life style habits need to be established in childhood to prevent these problems in adolescents and adults.

OK, then what is insulin resistance syndrome?
This common condition, results from the body being unable to respond normally to the pancreatic insulin it makes. Insulin is a hormone that is secreted into the blood stream after eating, in an amount that is generally proportional to the amount of carbohydrate consumed.

Muscles, fat and the liver are three of the main organs that are insulin sensitive and affected by rises in insulin levels. In muscles, insulin directs influx of glucose from the blood for energy. In the liver, insulin inhibits the breakdown and export of fats, the main energy fuel for muscles in between meals. In adipose or fat tissues, insulin inhibits breakdown of fat to high energy fatty acids. In persons with IRS, high levels of blood insulin initially build up to overcome the insulin resistance, and this in turn becomes associated with obesity and often a pigmented thickening of the skin about the neck, the arm-pits, abdominal skin folds and groin areas called acanthosis nigricans and/or an excessive formation of skin tags usually about the neck, eyes and arm pits.  Inside the body however, the insulin resistance/high insulin levels may cause more serious problems. It also contributes to fat accumulation in bodily fat stores.

So why do I (my child) have insulin resistance?
There are several known causes of the problem. In some persons with IRS, there is a defective signaling to the brain that they already have adequate fat stores and/or have had enough to eat after a substantial meal.

Recent studies have identified an increasing number of hormonal and metabolic signals involved.

• Overeating behavior can lead to onset of obesity from early life and, in turn,  IRS.

• In others, there is a primary problem affecting sensitivity to insulin actions, leading to IRS. In such cases, obesity becomes a complication of IRS rather than it’s cause.

• Specifically, some rare families have inherited defects in the insulin receptors on the surface of the insulin responsive cells in the body.

• Others can develop an antibody that attacks the insulin receptors and blocks them from responding normally to the insulin that the body produces. The latter persons commonly develop other immunological diseases such as systemic lupus erythematosis.

• Some unusual persons with IRS lack fat cells in their bodies. This condition is called lipodystrophy and results in a muscular like appearance since there is a lack of fat covering the muscles.

• Another cause  may be genetic disorders whereby hormonal signaling from body fat stores is unable to suppress appetite. Such a defect can lie at the level of the fat cells themselves or else in the receptors of the brain that receive suppressed appetite or “satiety” signals.

• Rarely, there is an inability to make the neurotransmitter substances that suppress appetite or receive such signals within the appetite center of the brain-the hypothalamus.

• Other  persons have defects inside the insulin responsive cells of the body that impair the insulin signal from doing its job.  In all probability, there are a large number of genetic disorders that can lead to IRS, however once IRS has developed, it needs to be managed to prevent it’s complications. 

When all of the above known causes if IRS are considered together, they account for just a few percent of the IRS problem that we see at BioSeek Endocrine Clinics.

For most persons affected by IRS, it seems likely that the condition is strongly inherited, affecting as many as half the family members in every generation. This is called a dominant mode of inheritance, where as many as half the children of an affected parent may have the disease too. However, despite huge research efforts, the responsible genes remain largely unknown.

Whereas you or your child is likely to have such a gene defect too, the mere inheritance of the gene is insufficient by itself to cause IRS. There are predisposing environmental “life style” factors at work too. These important factors are lack of physical exercise and the eating of more calories than necessary for your body’s energy needs, especially in the form of carbohydrates and fats.

Persons with IRS are unusually prone to accumulate fat stores from foods that they eat, especially simple carbohydrates. Patients are often “carbohydrate addicted,” eating much lower amounts of calories, when simple carbohydrates are restricted but proteins and fats are not.

In a recent study of adults, calorie consumption went down 1000 calories per day when only simple carbohydrates were consumed. Under activity and over-eating leads to obesity, which worsens insulin resistance (especially just before the time of puberty or in the pubertal years) hastening the development of the full blown IRS.

Some ethnic  groups are unusually prone to IRS, and, in them, such problems as type-2 diabetes and high blood pressure (hypertension) have become epidemic. Native Americans  are a highly susceptible, with some of their regional groups having the highest incidence of type-2 diabetes in the world.

Other very IRS prone ethnic  groups are persons from the Indian subcontinent, of African descents, from the Caribbean where genes from both of the latter ethnic  groups are prevalent, from the Arabian peninsula  and from Polynesia. Hispanic populations are unusually prone to IRS also. The reasons for this appear to lie in the ability of the insulin resistance genes to create a survival advantage in times of starvation (“metabolically thifty genes”), but which lead to obesity in times of plenty.

Thus, in some ethnic  groups who have been repeatedly exposed to starvation over generations, such genes have accumulated in frequency over long periods of time since those that did survive, would be unusally well-endowed with these 'thrifty' genes.

In a more affluent setting, where food availability is not a problem, obesity results in such persons. Thus nomadic peoples of Africa, North America and the Arabian peninsula who,  for example had a low incidences of type-2 diabetes in their natural habitats, develop a high incidence of obesity and diabetes once they became urbanized.

The BioSeek clinics has named this “the urbanization syndrome” where economic advance is having a devastating health effect of these IRS prone populations. It should be noted that all ethnic  groups are afflicted by IRS.

What problems are caused by of the insulin resistance syndrome?

• A principal problem is obesity. Obesity as measured by the body mass index (BMI). BMI is the weight in kilograms (Kg) divided by the square of the height in meters. BMIs over 27 in adults indicate overweight and > 30 obesity.

• Children with IRS are often tall and outgrow their parents. This is due to excessive levels of bioactive insulin and likely insulin like growth factors (IGFs).

• Acanthosis nigricans is a troublesome hyperpigmentation, that can give an appearance like an unwashed neck, but it is only a cosmetic problem which will not wash off. It is a hallmark of underlying IRS however. Some patients develop excessive numbers of skin tags.

• Dyslipidemia is disturbed lipids or fats in the blood. A fat containing molecule produced in the liver named very low density lipoprotein (VLDL) is involved, and blood levels of triglycerides are elevated (>140mgs/dl) and high density lipoprotein (HDL) or “good” cholesterol levels are low (<40mgs/dl). This profile is associated with premature atherosclerosis if left untreated. Elevations of bad cholesterol (LDL) are not raised because of IRS but some patients may coincidentally have elevated LDL because of another common genetic disorder.

• Hyperadrenalism: Cortisol and weak male hormones (androgens) are often secreted prematurely (premature pubarche) in childhood and excessively leading to red and later pale “stretch” marks or striae appear on the skin of the lower abdomen, shoulders and hips. This often begins around 8 years of age but can be earlier or later by a year or two.

• Polycystic ovarian syndrome (PCOS) is common in females with IRS. The ovaries overproduce male hormones (androgens) resulting in increased male pattern hair, acne, reduced menstrual periods and infertility. The affected ovaries can develop cystic changes that can be seen by ultra-sound examinations.

• Allergies: Asthma is unusually common with IRS as is eczema but less often.

• Hypertension or high blood pressure (BP) can be a complicating problem, especially in persons of African descent. It is due to an inability of the kidney to rid the body of excess salt. As salt accumulates, so does water expanding the blood volume and raising resting BP especially diastolic BP
• Type-2 diabetes is a common complication as the patient ages, and results from the pancreatic insulin secreting b cells failing to keep up with the demands of excessive insulin secretion needed to overcome insulin resistance.At first, blood glucose levels rise excessively only after eating, but eventually fasting blood glucose levels become excessive too.

• Atherosclerosis is the most serious complication, and is accelerated by dyslipidemia, high blood pressure, and diabetes. In the long term, this is a principal reason why IRS must be aggressively treated to prevent such problems.

• Tendency to thromboses or clotting within a blood vessel aggravates the risks from atherosclerosis.

• Fatty liver or steatosis is a common problem that can lead to cirrhosis. Non alcoholic hepatosteaosis (NASH) is the name given to this problem. Gall stones and attacks of pancreatitis may also occur also when triglyceride levels rise excessively.

• Gout occurs at an increased frequency in adults.

• Nephropathy appears to result in some patients and worsened by diabetes. This is tested for by small amounts of protein (microalbumin) leaking into the urine.  

Wow, this is a lot of trouble for me or my child. What can I do about it?
The answer happily, is that you can do a great deal. The remedy lies with diet, exercise and medication and prevention of progression of the syndrome. Once insulin resistance has developed, you have a problem that needs to be managed for life. This requires nothing less than a permanent life style change.