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Metabolic Syndrome or Pre-diabetes? Neither…Early Diabetes

In honor of National Diabetes Awareness month, we would like to share posts and articles from various people who work with or are directly affected by diabetes.

To start us off, we asked Robert F. Dons, MD, PhD to share his thoughts  about the different terms used to describe diabetes or prediabetes.

I personally have had the pleasure of meeting Dr. Dons on a few occasions. Not only is he brilliant, he is also very kind.  It was apparent from our very first meeting that Dr. Dons cares deeply for his patients and goes above and beyond to ensure they are getting the best quality of care. I think what impressed me the most about Dr. Dons was his enthusiasm for patient education.  In addition to being one of the best Endocronologist I have met, here are some other fun facts about Dr. Dons.

  • University of Illinois MD graduate 1973, PhD biochemistry graduate 1975
  • Fellowship in Endocrinology, Diabetes and Metabolism at the National Institutes of Health 1982
  • Private practice of clinical endocrinology for more than 10 years in San Antonio
  • Published author of definitive textbook about tests used by endocrinologists for making endocrine diagnoses
  • Endurance athlete –runner – working on 3rd half marathon – projected finish time (62 years old)  in 2 hours 35 min

Please feel free to write questions about the article or Dr. Dons in the comment section below

Metabolic Syndrome or Pre-diabetes? NEITHER! What counts is “Early Diabetes”



Many folks have heard the term ‘borderline’ diabetes. Some have been told that is what they have. If you are one of them and have looked up what it means, you will probably come across the terms metabolic syndrome and ‘pre-diabetes’. You may see the term ‘early diabetes’ as well and that is what I wish to focus on in this article.

So what do all these terms mean? Do they all refer to the same thing or do they have significantly different meanings? Even more importantly, what is the underlying cause of these conditions, what does having one or more of these conditions mean in terms of future health and what can be done about them?

First, I would like to get rid of the term ‘borderline diabetes’. It can mean completely different things to patients and their doctors. In my opinion, the term is almost meaningless. One might use the phrase ‘sugar problem’ or a ‘touch of sugar’ and get the same level of information. In brief, serious problems with diabetes mellitus (DM) can be overlooked when this term is used or an over diagnosis of diabetes can be made when only a transient and insignificant change in blood sugar is detected.

Knowing something about sugar in the blood stream is important to understanding these terms. Sugar in the blood should always be called glucose. When measuring glucose the difference between glucose in the plasma versus that in whole blood must be understood. Whole blood is defined as plasma mixed with red cells; a plasma sample has had the red cells removed. Measurements done in laboratories on receipt of venous whole blood samples and those done from blood samples obtained from a finger may result in a report of either plasma or blood glucose level. In general, reports of plasma glucose are preferred since they are more accurate and have become the universal standard. These measurements are higher than those obtained from whole blood. The glucose levels used throughout the rest of this article will be those found in plasma.  

Many years ago, the term “Syndrome X’ was used to describe the mysterious coexistence of five medical problems which are now collectively called ‘metabolic syndrome’. They were hypertension, elevated fasting glucose, elevated triglycerides, low HDL and obesity. These problems are now precisely defined and are recognized as important markers of a serious, but common, condition known as insulin resistance. Much research has gone into understanding more about insulin resistance, but much more remains to be known.

It is important to know that having one or more of the features of metabolic syndrome does not mean that you are diabetic. On the other hand, most diabetics who are not dependent on insulin therapy have one or more of these problems. In the last few years, having one or more of these problems has led physicians to label a patient ‘pre-diabetic’. At first, some authorities thought that at least three of the five problems had to be present before this ‘diagnosis’ could be entertained. This idea was very arbitrary and has been abandoned. In my opinion, there is no practical set of features which defines a condition known as pre-diabetes. Thus, I discard this term much like the term ‘borderline’ diabetes.

So what are the features of metabolic syndrome? They are described in detail by the International Diabetes Foundation (IDF) and are presented in my book Endocrine and Metabolic Disorders Clinical Lab Testing Manual 4th Edition 2009. In this book are described a multitude of other tests relevant to the diagnosis of diabetes mellitus (DM) and related conditions.

Precise definitions of the problems constituting the metabolic syndrome, as formalized in 2005, are as follows:

  1. Hypertension with a systolic blood pressure or top number equal to or above 130 mm Hg or a diastolic or bottom number equal to or higher than 85 mm Hg
  2. Elevated fasting plasma glucose on arising equal to or greater than 100 mg/dL
  3. Elevated triglycerides, a lipid fraction in the blood, equal to or greater than 150 mg/dL, may be toxic to the beta cells of the pancreas by breaking up into free fatty acids.
  4. Low HDL (high density lipoprotein), defined as less than 40 mg/dL for men and less than 50 mg/dL for women
  5. Obesity, defined as an increase in abdominal girth (not waist size!) equal to or exceeding the gender and ethnic ‘cutoffs’ decided by the IDF, is perhaps the most important factor. These ‘cutoffs’ range from 37 inches for European men to 31 inches for Asian women. Other cutoffs popularly used in the U.S. are 40 inches for men and 35 inches for women.


At this point I would like to focus on the fasting and after meal glucose levels as markers of ‘early diabetes’. First of all it must be recognized that the term ‘early diabetes’ has not been precisely defined and that experts in the science of metabolism may argue for different definitions than I present here. Nonetheless, from my studies and experience, I believe that what follows is a practical and helpful guide to deciding if an individual actually has ‘early diabetes’.

When it comes to the fasting plasma glucose (FPG) level on arising from sleep, several factors must be taken into consideration. The first of these is the timing of the last intake of food or drink. While several hours (more than 2) is all it takes to bring the glucose into a ‘steady state’, a prolonged period of fasting (not eating or drinking anything, usually for more than 14 hours) can result in a falsely lower or non-diagnostic FPG. Another factor is the amount of fat stored in the liver. Higher amounts of fat are found in the livers of more obese persons and higher FPG will occur. Stress in general, sleep disturbances or sleep apnea syndromes also raise the FPG. If someone has absolutely no problem with diabetes or any of the other problems noted above, a normal FPG rarely is greater than 85 mg/dL. Early diabetes may be suspect at a FPG of greater than 94 mg/dL and is almost certainly present at 100 mg/dL or more while ‘overt’ DM is a level of 200 mg/dL or more.

So what about after meal glucose levels? It is important to differentiate these levels from ‘random’ glucose levels obtained anytime during the day. Scientifically, the after meal glucose is called a ‘post-prandial’ or post-cibum (pc) glucose and is measured in a blood sample obtained 2 hours from when the last meal was started. It is also important to recognize that this level is completely different from the glucose levels obtained after a glucose tolerance test or GTT. The GTT is a research test which involves the oral intake of an artificially high concentration of glucose (50 to 100 grams in water) over a short time followed by measurement of glucose levels at various times up to 5 hours. The GTT has only one use clinically and that is in pregnancy to help with the early diagnosis of gestational DM.

Post-prandial or pc glucose levels can go up in response to a variety of factors such as increased stress, high proportion of carbohydrates to protein and fat in the meal, a higher proportion of ‘simple’ to ‘complex’ carbohydrates in the meal, an inadequate number of calories eaten in the past few days followed by an excess carbohydrate intake, a faster rate of stomach emptying and a low-level of activity. However, when it comes to the diagnosis of early DM these factors are not critically important. Importantly, when an individual has a ‘normal’ FPG and abnormally high 2 hour pc glucose, the possibility of early DM is very likely.

If the 2 hour pc or random glucose level is 200 mg/dL or greater and is confirmed on repeat testing, the diagnosis of overt DM is established. Glucose values pc less than 200 mg/dL may or may not indicate DM. As a practical matter, in someone who is not known to be diabetic, a 2 hour pc glucose over 140 mg/dL prompts further study with repeat testing of the pc glucose and the use of another test called the hemoglobin A1c (HgbA1c). It is not unusual for someone to have a single determination of pc glucose up to 180 mg/dL and not be diabetic especially if the factors noted above or diabetogenic (e.g., steroid) medications are involved.

In the diagnosis of early diabetes, the HgbA1c is an invaluable, but occasionally misleading, test. The HgbA1c allows an estimation of the average glucose level over the past 6 to 8 weeks. It is a fully integrated value reflecting both all the highs and all the lows in glucose. This test is capable of such a feat by using the capacity of the protein hemoglobin in red cells to combine with free glucose which binds to the hemoglobin in an irreversible manner. Thus, the higher the glucose level, the more binding and the higher the percentage of hemoglobin converted into HgbA1c. While a truly non-diabetic level of HgbA1c has not been established, the following cutoffs are of practical use. A HgbA1c of less than 5.7% is not in the diabetic range unless the patient is anemic or has rapid turnover of red cells which falsely lowers the percentage of glucose bound to the hemoglobin molecule.  A HgbA1c of 6.5% or greater is consistent with overt diabetes if other tests confirm it. HgbA1c in between these levels are indeterminate, but highly suspect for the diagnosis of early diabetes especially if one or more features of the metabolic syndrome is present.

In summary, there are practical criteria for the diagnosis of early diabetes.  These criteria are a Hgb A1c of between 5.8% and 6.5%, a confirmed FPG of more than 100 mg/dL, and a 2 hour pc glucose of more than 140 mg/dL. Once the diagnosis is made, treatment, particularly cost-effective lifestyle changes, can get started. This is important because bringing down the glucose can help preserve the insulin secreting capacity of the pancreas. Medications can help to accomplish this goal – an extension of the life of the pancreas. Lifestyle changes, particularly weight loss, help reduce triglycerides and its components known as free fatty acids which are toxic to insulin secreting cells in the pancreas.

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