Glucose Intolerance (Problems with Blood Glucose Control)

What is glucose intolerance?

Glucose intolerance is a broad term encompassing several conditions that leads to abnormally high blood glucose levels (hyperglycemia). It is often confused with impaired glucose tolerance (IGT), one of the conditions listed under the term glucose intolerance. Sometimes glucose intolerance is also mistaken for a digestive disorder where glucose in not digested or absorbed, like with lactose intolerance or gluten intolerance. However, glucose intolerance actually means conditions where the body is not processing glucose as it should leading to elevated glucose levels in the blood.

How common is glucose intolerance?

Since glucose intolerance is a broad term that includes conditions like diabetes mellitus, it is fair to say that the glucose tolerance is common and on the rise globally. The second most common form, diabetes mellitus, is closely linked to genetic factors and obesity. About 20 million people in the United States suffer with diabetes mellitus and it is estimated that about 30% cases are undiagnosed. Even more common is impaired glucose tolerance (IGT) but the majority of cases are never diagnosed until it has progressed to diabetes.

Types of Glucose Intolerance

Glucose intolerance includes several categories :

  • Diabetes – type 1 and type 2 diabetes mellitus and gestational diabetes (diabetes of pregnancy)
  • Impaired glucose metabolism – impaired glucose tolerance and impaired fasting gluse

In addition, there may be other specific types of diabetes that arise with certain conditions like liver disease.

Diabetes mellitus

In diabetes mellitus, there is either a lack of insulin (type 1), diminished response to insulin (type 2)  or the presence of high levels of other hormones that affect insulin activity (gestational). While gestational diabetes may reverse on its own after pregnancy, type 1 and type 2 diabetes mellitus are usually permanent. Other types may be associated with diseases of the liver or gut where glucose is absorbed and processed.

Impaired glucose metabolism

The two types of impaired glucose metabolism – impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) – are commonly referred to as pre-diabetes. This means that these conditions tend to precede the onset of diabetes mellitus if there is no intervention. With impaired fasting glucose, the blood glucose levels are elevated during fasting – a period of no food intake for several hours like after waking up from sleep. In impaired glucose tolerance, the body is unable to keep the blood glucose levels within the normal range shortly after food intake.

Problems with Glucose Metabolism

Glucose is the simplest sugar used in the body for energy. During the course of digestion, complex carbohydrates are broken down into smaller carbohydrates and eventually into glucose, if not in the gut then in the liver after absorption.

Although glucose is necessary to sustain life processes, high levels of glucose can damage cells in the body. Normally the level of glucose in the blood is mainly controlled by the hormone insulin which is secreted by the pancreas. Insulin ‘encourages’ cells to take in more glucose, thereby removing it from the blood. It also stimulates the liver to stop releasing more glucose, promotes its storage and even affects digestion to reduce intake of new glucose.

In glucose intolerance the body cannot control the blood glucose levels within the normal range. Elevated blood glucose levels may not be present throughout the day. Instead the disturbance can affect the way the body regulates the blood levels shortly after eating when the blood glucose levels are the highest, or after a prolonged period of no food intake when the blood glucose levels should technically be the lowest. It may not necessarily be a problem with insulin itself but the way the body’s cells respond to insulin.

Signs and Symptoms

Depending on the type of glucose intolerance, there may be varying symptoms. In pre-diabetes states, like impaired fasting glucose and impaired glucose tolerance, there may be no overt signs and symptoms. This is one of the main reasons that patients never seek medical attention and the conditions remain undiagnosed until discovered upon routine screening or when diabetes mellitus sets in.

Symptoms may include :

  • Polydipsia – increased thirst.
  • Polyuria – passing of large volumes of urine defined by frequent urination.
  • Polyphagia – increased appetite.
  • Fatigue.
  • Unintentional weight loss.

More severe symptoms may be seen with dehydration or ketoacidosis. Once complications arise, patients may report :

  • Poor wound healing.
  • Recurrent infections.
  • Visual disturbances.
  • Abnormal sensations like “pins and needles”, tingling and numbness.
  • Swelling of the ankles, feet and abdomen.

Causes of Glucose Intolerance

Although there is an inability to maintain the blood glucose levels within a normal range, the exact cause may be unknown. Commonly implicated etiological factors and risks for the development of glucose intolerance includes genetic factors and obesity. However, there are various other possible causes and risk factors.


Various genes have been implicated in the development of glucose intolerance. This is often inherited making a family history of diabetes one of the strongest risk factors. Genetic defects may affect the function of the beta cells of the pancreas which produces insulin. Diabetes is also more likely to occur in certain genetic syndromes like Down syndrome and Turner syndrome.


A higher body fat content may affect normal glucose tolerance and ultimately contribute to diabetes mellitus. Obesity may have a genetic component, however, it is often due to lifestyle particularly a high calorie diet and physical inactivity.


One of the main hormone states where the action of insulin is disrupted is in pregnancy. This is a physiological state. However, a range of endocrine diseases may also contribute to diabetes mellitus by blocking the action of insulin. This includes conditions like Cushing syndrome and hyperthyroidism.


Glucose intolerance has been linked to the intake of several different chemicals, most of which are consumed in the form of drugs. This includes medication like corticosteroids, oral contraceptives, thiazides and antiretroviral drugs.


Pancreatic diseases are by far the most likely to lead to glucose intolerance as the production and secretion of insulin is affected.  This includes pancreatitis, traumatic pancreatic injury, pancreatic cancer and surgery to the pancreas. Certain infections may lead to beta cell destruction such as rubella (German measles) and mumps.

Tests and Diagnosis

 The two most effective means of diagnosing glucose intolerance is by measuring the blood glucose levels, particularly during an oral glucose tolerance test, and glycated hemoglobin (HBA1C). The former is often preferred to confirm pre-diabetes although HBA1C levels may also be higher in patients with HBA1C.

Blood Glucose Readings

Normal blood glucose levels should not exceed 100mg/dL (fasting) and 140mg/dL two hours after the oral administration of a 75g glucose load. The relevant type of glucose intolerance is diagnosed based on the following readings :

  • Impaired fasting glucose : fasting blood glucose level is >99mg/dL (100mg/dL onwards) but <126mg/dL.
  • Impaired glucose tolerance : 2 hour blood glucose levels are >139mg/dL (140 mg/dL onwards) but <200mg/dL.
  • Diabetes mellitus :
    – Fasting level > 125mg/dL (126mg/dL onwards), or
    – 2 hour level > 199mg/dL (200mg/dL onwards), or
    – two random blood glucose levels above 199mg/dL (200mg/dL onwards).

HBA1C Readings

Glycated hemoglobin (HBA1C) is a reflection of the blood glucose levels over a 6 to 8 week period. The readings for glucose intolerance are as follows :

  • Pre-diabetes : 5.7% to 6.4%.
  • Diabetes : >6.4% (6.5% onwards).

Glucose Intolerance Treatment

Where the cause of glucose intolerance can be identified, it should be treated and the glucose tolerance may return to normal. Attending to modifiable risk factors with lifestyle measures – exercise, diet, smoking cessation, alcohol reduction – may be sufficient to reverse the pre-diabetes or at least delay the onset of diabetes.  Metformin used by patients with pre-diabetes may be able to  reverse diabetes mellitus. Lifestyle measures should also be continued in diabetes mellitus. Even though it may not reverse the condition, it can greatly improve glucose tolerance and delay the onset of diabetic complications.


Medication for the treatment of diabetes is essential. Oral medication includes :

  • Sulfonylureas and other secretagogues stimulates the release of insulin from the beta cells of the pancreas.
    – Glimepiride
    – Glyburide (glibenclamide)
    – Glipizide
    – Gliclazide
  • Biguanides (metformin) decreases glucose production in the liver and increases the uptake of glucose by cells.
  • Thiazolidinediones increases the sensitivity of fat and muscles cells to glucose thereby increasing its uptake.
    – Pioglitazone
    – Trovaglitazone
    – Rosiglitazone
  • Alpha-glucosidase inhibitors blocks the digestive enzymes that breaks down carbohydrates.
    – Acarbose
    – Miglitol
  • Incretin mimetics mimis naturally occurring incretins which increases insulin secretion along in accordance with the ingested glucose.
    – Exenatide
    – Liraglutide
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors enhances the effects of incretins and delays its breakdown.
    – Sitagliptin
    – Saxagliptin
  • Amylin analogues (pramlintide) mimic amylin which is secreted with insulin which slows down digestion and release of glucose by the action of the hormone glucagon.


Type 1 diabetics need insulin since their body does not produce the hormone. Only a small proportion of type 2 diabetics require insulin, usually once the beta cells produce too little or no insulin. There are different insulin preparations which may act for various periods of time. It can be classified as :

  • Ultra short-acting
  • Short-acting
  • Intermediate-acting
  • Long-acting
  • Ultra long-acting

References :

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