IMPAIRED GLUCOSE TOLERANCE – 

What is it? And Why is it So Important?

What is Impaired Glucose Tolerance (IGT)?

IGT is an impaired ability to handle an oral glucose load and, by inference, dietary carbohydrates.  IGT is an intermediate state between normal glucose tolerance and type 2 diabetes i.e. IGT is an early sign that a person’s carbohydrate metabolism is impaired. Most medical professionals do not regard IGT as a disease in its own right, merely a stage in the development of type 2 diabetes.

In people with IGT, the rise in blood glucose that occurs after eating carbohydrates is greater than normal (although not as great as in people with type 2 diabetes). The sharp rise in blood glucose following a meal is sometimes referred to as a ‘glucose spike’. Fasting blood glucose levels are normal or moderately raised.

How is IGT diagnosed?

IGT can be diagnosed from measurements of fasting blood glucose (measured first thing in the morning) and blood glucose two hours after consuming 75g glucose. This latter measurement is known as an oral glucose tolerance test (OGTT). Blood glucose measurements are usually expressed as the concentration of glucose in plasma i.e. the liquid phase of the blood that is left after the blood cells have been removed.

IGT is diagnosed if two criteria are met:

1.      Plasma glucose two hours after consuming 75g glucose is between 7.8 mmol/l and 11.1 mmol/l i.e. between ‘normal’ and ‘diabetic’ levels.

2.      Fasting plasma glucose level is less than 7.0 mmol/l i.e. it may be moderately raised, but it is below the threshold for diagnosis of diabetes.¹

What causes IGT?

IGT (and type 2 diabetes) results from a combination of impaired insulin secretion and reduced sensitivity of the body’s cells to insulin (insulin resistance). The observation that people with IGT have elevated post-meal blood glucose levels but near-normal fasting blood glucose suggests that the main defect in IGT may be impaired insulin secretion, although insulin resistance is also almost always present.

Individuals with IGT show a marked reduction in early insulin secretion i.e. the phase of insulin secretion that occurs prior to and immediately after eating.² This, compounded by the fact that insulin resistance increases the need for insulin, means that blood glucose levels rise excessively after a meal.

The loss of early insulin secretion in IGT and type 2 diabetes is the result of malfunctioning of pancreatic ß-cells. It has been suggested that early intervention might delay deterioration in ß-cell function and thus prevent or at least delay progression from IGT to type 2 diabetes. In the long-term, high blood glucose levels are toxic to ß-cells.³  Thus improved blood glucose control might help prevent further deterioration in ß-cell function.

Insulin resistance means that liver, muscle and fat cells have ceased to be highly sensitive to insulin. This means that insulin released at mealtimes does not stimulate a sufficient increase in glucose uptake. Insulin resistance is a common feature of individuals who are obese, particularly if they carry a lot of fat in the central (abdominal) region, are physically inactive, or had a low birth-weight, indicating fetal undernutrition. Genetic factors are also important. 

As people age, ß-cell function declines. There also tends to be a decrease in physical activity and an increase in body weight, increasing insulin resistance. Thus the prevalence of IGT (and type 2 diabetes) is much higher in older age groups.

How common is IGT?

The most recent estimate for the prevalence of IGT in the USA comes from the third National Health and Nutrition Examination Survey (NHANES) carried out in 1988-1994.⁴  A sub-sample of the survey’s participants, i.e. 2,844 adults aged between 40 and 74 years with no history of diabetes, received an OGTT.

Using WHO diagnostic criteria¹,15.6% of the survey’s participants were found to have IGT. The prevalence of IGT increased with age (see Figure 1). There was no significant difference in prevalence between men and women, but IGT was more common in Mexican-Americans (20.2%) than in blacks (14.0%) or whites (15.3%).

Figure 1. Prevalence of IGT in different age groups in the USA, according to NHANES 1988-94 [adapted from ref 4].

Prevalence estimates from other studies vary widely, depending on the culture of the population, the age group used and the study protocol.  However, it appears that the prevalence of IGT in Europe is similar to that in the USA. Worldwide, the highest prevalence rates are found in developing countries that have recently adopted a Western lifestyle.³

Why is IGT important?

IGT is a significant risk factor for cardiovascular morbidity and mortality. Research has shown that the macrovascular complications associated with type 2 diabetes (e.g. increased atherosclerosis, heart attack) begin to develop well before type 2 diabetes is diagnosed. By the time type 2 diabetes is diagnosed, macrovascular damage may already be well advanced.⁵ Thus it may be beneficial to treat IGT at an early stage.

Recent research indicates that blood glucose level two hours after consuming 75g glucose is a better predictor of mortality risk than fasting blood glucose. The DECODE (Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe) study, in which data were analysed from 13 prospective studies involving 25,000 participants, showed that raised blood glucose two hours after consuming 75g glucose is an independent risk factor for premature death.⁶

The DECODE study⁶ showed that people with type 2 diabetes were more than twice as likely to die during the follow-up period than people with normal glucose tolerance. People with IGT were over 50% more likely to die during follow-up than people with normal glucose tolerance. However, as there were four times as many people with IGT as with diabetes, there were more premature deaths attributable to IGT than to diabetes.

Figure 2. Effect of fasting plasma glucose level and plasma glucose level two hours after consuming 75g glucose on risk of death within follow-up period: results from the DECODE study [Adapted from ref 6].

IGT is often associated with a syndrome known as the Metabolic Syndrome, Insulin Resistance Syndrome or Syndrome X. This syndrome is a cluster of inter-related cardiovascular risk factors, including hypertension, high LDL-cholesterol, and low HDL-cholesterol, which greatly increases cardiovascular risk.⁷

Progression to type 2 diabetes

Some people who develop IGT will revert to normal glucose tolerance. Others will remain in a state of IGT. However, once IGT has developed, the body’s ability to deal with dietary carbohydrates tends to continue to decline, ultimately resulting in type 2 diabetes. Prospective (follow-up) studies looking at how people progress after IGT is diagnosed suggest that 3.6-8.7% of IGT sufferers will develop type 2 diabetes every year.^8,9 This deterioration is accompanied by increased risk of macrovascular and microvascular complications.

The main risk factors for progression from IGT to type 2 diabetes are higher fasting and/or post-meal blood glucose levels, obesity (particularly central obesity) and physical inactivity. ^8,9  People at particularly high risk for developing type 2 diabetes should be screened for diabetes at regular intervals, so that treatments can begin at an early stage. Patients with IGT are also the ideal population to use in clinical trials in diabetes prevention.

Treatment of IGT

People with IGT are encouraged to increase their physical activity level, aim for a healthy weight, and follow a healthy, balanced diet.  The vast majority of people with IGT are not on medication. Lifestyle management reduces insulin resistance and therefore diminishes the load on the b-cell (i.e. reduces the amount of insulin that b-cells have to produce). Studies have shown that very intensive counseling about weight loss, healthy eating and exercise reduces progression from IGT to type 2 diabetes¹⁰ but that less intensive counseling is ineffective.

Large-scale studies are currently being conducted to investigate whether drug therapies are effective at preventing people with IGT developing type 2 diabetes and CVD.