Pre-Diabetes

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Pre-Diabetes
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Pre-Diabetes is a very common medical condition which unfortunately remains undiagnosed. About 60 million Americans are estimated to be suffering from it and yet don't know.

You have Pre-Diabetes if you have one of the following two conditions:

Impaired fasting Glucose (IFG)

or

Impaired Glucose Tolerance (IGT)



Impaired fasting glucose (IFG) and Impaired glucose tolerance (IGT) are precursors for diabetes and therefore, are also known as pre-diabetes. From a medical standpoint, these conditions should be regarded as early diabetes.

The development of diabetes is a long process that usually spans a period of 10-20 years. During this time, the process of insulin resistance is going on. Insulin resistance is the underlying cause for IFG and IGT.



What is Impaired Fasting Glucose?

You have impaired fasting glucose if your fasting blood glucose is more than 100 mg/dl.



How is Impaired Glucose Tolerance diagnosed?

Impaired glucose tolerance is diagnosed on a 2 hours oral glucose tolerance test. In many patients with impaired glucose tolerance, a routine fasting blood glucose test is often normal. Therefore, this important condition can be missed if an oral glucose tolerance test is not performed.

An excellent article published in 1999 in the Archives of Internal Medicine, compared the fasting blood glucose test versus the 2 hours oral glucose tolerance test.

In this landmark study, known as the Decode study, a total of 22,514 individuals were followed for a mean duration of 8.8 years. The authors looked at the number of deaths due to various stages of glucose abnormalities (impaired glucose tolerance, impaired fasting glucose, and diabetes). A large number of deaths were attributable to impaired glucose tolerance. Many of these individuals had a normal fasting blood glucose.

They would not have been diagnosed if only the fasting blood glucose was given.

Unfortunately, most physicians in the US rely only on the fasting blood glucose. They don’t take the extra step of doing an oral glucose tolerance test.

Consequently this important medical condition with serious complications remains largely undiagnosed.

One purpose of writing this website is to educate the public about these medical facts so they can be better advocates of their health.

The 2 hours Oral Glucose Tolerance Test is done in the morning after an overnight fast of about 12 hours. A blood sample is drawn for glucose measurement. The patient is then given a glucose drink, which contains 75 grams of glucose. Two hours later, another blood sample is drawn for glucose measurement. The patient does not eat or drink during this two hours period.

The test results are interpreted as follows:



Fasting blood glucose Blood glucose at 2 hours Interpretation of Test

70 – 100 mg/dl Less than 140 mg/dl Normal

70 – 100 mg/dl 140 – 200 mg/dl Impaired Glucose Tolerance

70 – 100 mg/dl More than 200 mg/dl Diabetes



A fasting blood glucose of 100–125 mg/dl is called Impaired Fasting Glucose.

A fasting blood glucose of more than 125 mg/dl is diagnostic for diabetes.





Why is it so important to diagnose impaired glucose tolerance?



Impaired glucose tolerance is just tip of the iceberg. In fact, these patients are suffering from a much more complicated disease process called insulin resistance. These patients are at high risk for heart disease, stroke, dementia, peripheral neuropathy and leg amputations.

A number of excellent scientific studies clearly show that patients with impaired glucose tolerance have a markedly increased risk for heart disease. These famous studies include the Chicago Heart Study , the Rancho Bernardo Study , the Honolulu Heart Study , and the Funagata Diabetes Study . These landmark studies were published in the journal of the American Diabetes Association, Diabetes Care in 1997, 1998 and 1999 respectively.

Data from the Second National Health and Nutrition Examination Survey Mortality Study was recently analyzed by the researchers at the Johns Hopkins University School of Medicine. It was concluded that in the US population, there is 40% greater risk for cardiovascular mortality in individuals with impaired glucose tolerance. This study was published in 2001 in Diabetes Care.

In the Hoorn Study, people in the Dutch town of Hoorn with impaired glucose tolerance were found to have a higher risk for cardiovascular mortality. This study was published in 1999 in the prestigious Europian journal, Diabetologia.

Patients with impaired glucose tolerance are also at high risk for narrowing of the carotid arteries, which places them at risk for stroke, mini-stroke and dementia. Yamasaki and his colleagues did an excellent study published in Diabetologia in 1995. Utilizing ultrasounds of carotid arteries, they demonstrated that patients with impaired glucose tolerance have narrowing of these blood vessels.

In the Hoorn Study, impaired glucose tolerance was found to be a risk factor for the narrowing of the carotid arteries.

In my clinical experience, impaired glucose tolerance is frequently found in patients with stroke and dementia.

Impaired glucose tolerance is the underlying cause for peripheral neuropathy in a number of patients who do not have any obvious cause for their peripheral neuropathy. Symptoms of peripheral neuropathy include numbness, pain, tingling or a burning sensation, usually in the feet and at times, in the fingers as well.

In three recently published studies , investigators looked at patients with peripheral neuropathy of unknown cause and gave them an oral glucose tolerance test. In these studies, a significant number of patients had impaired glucose tolerance as the cause for their neuropathy. Authors of these studies recommend using an oral glucose tolerance test in patients with peripheral neuropathy of an unknown cause.

My own clinical experience certainly confirms these observations. I have seen a number of patients who were diagnosed with peripheral neuropathy, but no cause could be found. These patients had undergone extensive diagnostic testing, except for the oral glucose tolerance test. Once I ordered the oral glucose tolerance test, these patients were diagnosed with impaired glucose tolerance or diabetes.

Patients with Impaired Glucose Tolerance are at high risk for the development of diabetes. About 10% of patients with impaired glucose tolerance become diabetic every year. Therefore, within ten years, almost all patients with this condition will become diabetic.

Progression to full-blown diabetes can be prevented in these patients if this condition is properly diagnosed and aggressively treated.

Like diabetes, impaired glucose tolerance is a disease and can easily be diagnosed with an Oral Glucose Tolerance test. The importance of impaired glucose tolerance as a disease state was emphasized by an excellent article published in Diabetes Care in 1999 .

Sadly, most physicians do not order the Oral Glucose Tolerance test and therefore, this very important condition remains undiagnosed in a majority of patients. In a recently published article in Diabetes Care in 2002, the author reviewed extensive scientific evidence of the significance of diagnosing impaired glucose tolerance in the clinical practice .

If we are serious about preventing devastating medical conditions such as diabetes, heart disease, stroke, peripheral neuropathy, dementia, kidney failure, blindness and leg amputation, physicians must start using the Oral Glucose Tolerance test.



Who is at risk for Impaired Glucose Tolerance?



Several scientific studies have shown that the decline in glucose tolerance usually begins in the third decade and continues throughout adult life.

In a study published in July 2001 in Diabetes Care , Japanese investigators reviewed data from 13,694 individuals who underwent a 2 hours oral glucose tolerance test during a health screening in Japan between 1994 to 1999.

In this study, the fasting blood glucose level, aging, obesity, high triglycerides level and blood pressure were strongly associated with impaired glucose tolerance.

However, there were a number of individuals who had a normal fasting blood glucose, but turned out to have impaired glucose tolerance on an Oral Glucose Tolerance Test, especially in older individuals.

Aging is a strong predictor of impaired glucose tolerance. It is estimated that there is a mean increase of 9.4 mg/dl per decade in the values of 2 hours post meal blood glucose, starting at age thirty. The authors of this article stress the importance of performing an Oral Glucose Tolerance Test, especially in older individuals.

In another large study from Sweden published in 1999 in Diabetes Care 21,057 men and women aged 30-60 years underwent an oral glucose tolerance test. The risk for impaired glucose tolerance was higher among individuals with obesity, high blood pressure, high triglycerides level and a family history of diabetes. However, more than 70% of individuals did not have any family history of diabetes. Also impaired glucose tolerance was present in a number of non-obese individuals.

For example, a 65 years old, person might have impaired glucose tolerance even if he/she is a thin person. On the other hand, a young 35 years old might have impaired glucose tolerance if he /she is overweight.



The risk for impaired glucose tolerance is markedly increased if:



You are over the age 30

You are overweight, especially if your waist-line is more than 40 inches if you are a male or more than 35 inches if you are a female.

You have a sedentary lifestyle.

You have high blood pressure

Your triglycerides level is elevated (more than 150 mg/dl)

Your HDL cholesterol level is low (less than 40 mg/dl if you are a male or less than 50 mg/dl if you are a female).



Who should be tested for Impaired Glucose Tolerance?

Any individual with the following conditions should have an oral glucose tolerance test to diagnose the state of impaired glucose tolerance:

Everybody over the age of 30

Obese individuals, even under the age of 30.

People with high blood pressure

People with low HDL cholesterol.

People with high triglycerides.

People with a fasting blood glucose between 100 – 125 mg/dl. (A fasting blood glucose greater than 125 mg/dl is diagnostic for diabetes and these patients do not need an oral glucose tolerance test).

People with coronary artery disease, including those who have had angioplasty, stent placement or heart bypass surgery.

People with stroke, mini-stroke, dementia or memory loss.

People with peripheral vascular disease, also known as poor circulation in the legs.

People with peripheral neuropathy, which often manifests as pain, tingling or numbness in feet, which is usually worse at night.

Women with Polycystic Ovary Syndrome

Women with a history of gestational diabetes



Treatment of Impaired Glucose Tolerance:

Impaired glucose tolerance is a marker for Insulin Resistance Syndrome. Therefore, the treatment should aim to reduce insulin resistance and prevent complications of Insulin Resistance Syndrome such as heart attack, stroke and dementia. This treatment should also prevent the progression to frank diabetes.

Therefore, the goals of treatment of impaired glucose tolerance are:

To prevent heart attack, stroke and dementia.

To prevent progression to frank diabetes.

Try to revert to normal glucose tolerance



Treatment of impaired glucose tolerance consists of:

Diet

Exercise

Vitamins, Herbs, Drugs

Diet and exercise are important, but by themselves will not achieve the above mentioned goals.

Several studies have investigated the goal of preventing progression to frank diabetes in these patients. One recent landmark study, Diabetes Prevention Program (DPP), was carried out in the U.S. in 2001. In this study, 3234 people with impaired glucose tolerance were enrolled and randomized into one of the three protocols:

Intensive diet and exercise group (150 minutes of exercise/week and 5-7% weight loss)

Metformin 850 mg twice a day

Placebo.

During an average of 3 years of follow-up, approximately 29% of the placebo group, 14% of the intensive diet and exercise group and 22% of the metformin group developed diabetes.

The risk for progression to diabetes was reduced by 58% in the intensive diet and exercise group and by 31% in the Metformin group. Metformin was mainly effective in younger individuals (between the ages of 24-44) or those with significant obesity (body mass index >35 kg/m2). Metformin was almost ineffective in older individuals (> 60 years of age) or in those who were less overweight (BMI < 30 kg/m2).

In my interpretation of this data, the risk for the progression from impaired glucose tolerance to diabetes was only cut in half with a rigorous diet and exercise.

Metformin alone did not appear to be very effective in achieving this goal, especially in older individuals.

Another medicine, Acarbose, was shown to reduce the risk of diabetes by 32% in the STOP-NIDDM trial . The most frequent side-effects to Acarbose were flatulence and diarrhea. Thirty one percent of patients on Acarbose and 19% on a placebo discontinued treatment early. This study was published in Lancet in 2002.

In real life, patients want a treatment strategy with better results. If I were to prescribe a certain strict regimen of diet and exercise to my patients and tell them that they have a 50-50 chance of preventing diabetes, I don’t think that many of them would follow my advice.

I want a strategy in which more than 80% of patients with Impaired Glucose Tolerance are able to prevent progression to diabetes. This strategy should also be able to prevent the complications of impaired glucose tolerance such as heart attack, stroke and dementia. One should also remember that impaired glucose tolerance itself is a serious disorder, indicating Insulin Resistance Syndrome and all it’s associated complications.





In my opinion, a strategy utilizing intensive diet, exercise and use of vitamins, herbs, and TZD (short for thiazolidinedione) drug appear to be the most promising approach.

Certain Vitamins and herbs have been shown to reduce insulin resistance in excellent scientific studies. I have put these good vitamins and herbs together in a formula which is available now as GLUPRIDE.



TZD (short for thiazolidinedione)

TZDs act by reducing insulin resistance. Troglitazone, a TZD drug, was used in the TRIPOD study . It was shown to reduce the risk for diabetes by 56%. This protective effect of troglitazone appeared to be present even 8 months after discontinuation of troglitazone. This study was published in Diabetes in 2002.

Troglitazone was also shown to revert impaired glucose tolerance back to normal in 80% of treated patients . This study was published in Diabetes Care in 1997.

In the DPP (Diabetes Prevention Program) there was a fourth treatment protocol initially, in which patients were placed on Troglitazone. This arm of the study was discontinued in June 1998 because of liver toxicity.

In 2000, Troglitazone was taken off the US market because of its association with liver toxicity. However, two other TZD agents, Actos and Avandia, have been available since 1999. More than 30 millions prescriptions of Actos and Avandia have been written. These two drugs are very safe as far as liver toxicity is concerned.

Studies are now under way using these drugs in patients with impaired glucose tolerance. It will be several years before the results of these studies become public.

In the meantime, we cannot allow patients to continue to suffer the complications of Insulin Resistance Syndrome without doing anything. It’s like watching a train wreck in slow motion.

Recently, I have been utilizing the following approach in treating my patients with impaired glucose tolerance.

I counsel them about a low carbohydrate diet and regular exercise for about 20-30 minutes every day.

In addition, I also use a TZD drug, either Actos or Avandia and Glucophage.

Please beware that at this time, Actos, Avandia and Glucophage (metformin) are approved by the FDA (Food & Drug Administration ) for the treatment of Type 2 diabetes, but not for impaired glucose tolerance.



The following actual case study from my practice illustrates Impaired Glucose Tolerance.



Case Study

A 74 years old male consulted me for uncontrolled high blood pressure. He had a lot of fatigue and also had to urinate frequently. He presumed that it was due to his prostate enlargement, for which he was operated on twice in the past.

He was diagnosed with high blood pressure 20 years ago. Since then, he had been under the care of numerous physicians. Although they treated his blood pressure, no one had thought to evaluate him for possible Insulin Resistance Syndrome.

Medication

Diovan 160 mg/day

Hytrin 1 mg / day

Nasonex nasal spray

Physical Examination

Blood pressure = 160/90

Weight = 186 Lbs. Height = 5 8” ; (about 20 Lbs. overweight )

Abdominal obesity was present.

Diagnosis

Because this patient had high blood pressure, I suspected Insulin Resistance Syndrome and wanted to evaluate him for other components of Insulin Resistance Syndrome.

I ordered a 2 hours Oral Glucose Tolerance test, the results of which were as follows:

Fasting
At One Hour
At Two Hours

Blood Glucose
92
177
142




A 2 hours blood glucose value above 140 mg/dl confirmed that he had Impaired Glucose Tolerance.

As you can see, this patient’s fasting blood glucose was perfectly fine. His impaired glucose tolerance would not have been diagnosed, had he not undergone a 2 hours oral glucose tolerance test.



Management

I had a long discussion with him about Insulin Resistance Syndrome and its complications. I started him on my treatment plan .

Now his 2 hours post-meal blood glucose stay around 90-100 mg/dl. (which are normal blood glucose values). He did not have any vascular events such as heart attack or stroke, even though he was at a high risk.

Now he is truly enjoying his golden years.