A guide to diagnosing and managing impaired glucose tolerance

According to the American Diabetes Association (ADA), patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are considered to have prediabetes.¹ These patients are thought to be at high risk for developing diabetes and cardiovascular (CV) disease.

The term “prediabetes” has often been used to refer to the metabolic syndrome, also known as “dysmetabolic syndrome,” “syndrome X,” or “insulin resistance.” Prediabetes has also been used to define patients at risk for type 1 diabetes mellitus who have autoantibodies to insulin or to insulinoma-associated protein 2 and glutamic acid decarboxylase but have not yet manifested the disease process.^2,3 The ADA clearly classifies those with IFG and IGT as prediabetics, regardless of the etiology of impaired glucose metabolism.

Q. How is prediabetes diagnosed?

A. Prediabetes is not a disease. It is recognized by the ADA as an intermediate state in which glucose metabolism is compromised and the individual is at high risk for CAD and diabetes. The initial step in identifying individuals who are prediabetic is to distinguish those with risk factors or those who present with associated symptoms of either diabetes or CAD. Identification of persons at high risk for diabetes and CV disease will offer a great opportunity for intervention, and intervention has the potential to decrease the tremendous human and health-care costs of these two disease processes.

The definitive recognition of prediabetes, however, can only be made by measuring the fasting blood glucose (FBG) level or the plasma glucose concentration two hours after administration of an oral-glucose tolerance test (OGTT). Individuals with an FBG between 100 and 125 mg/dL (5.6-6.9 mmol/L) have IFG. Individuals who have a plasma glucose level of 140-199 mg/dL (7.8-11.1 mmol/L) two hours post glucose challenge have IGT.¹

Q. Who develops prediabetes?

A. It is estimated that between 10% and 15% of adults in the United States have either IFG or IGT.4 Analysis of data from the Third National Health and Nutrition Examination Survey, however, provides a more accurate picture for older, overweight adults — those aged 45-74 years with a BMI Æ 25. This analysis shows that 17.1% of these individuals had IGT, 11.9% had IFG, and 5.6% had both. Based on these percentages, the survey researchers estimated that in 2000, approximately 12 million overweight Americans were suffering from prediabetes.⁵

Q. What is the relationship between prediabetes and the metabolic syndrome?

A. A large number of individuals in the prediabetic state may show the hallmark signs and symptoms of the metabolic syndrome. They may be obese and have impaired fasting lipid profiles, at a minimum, or CV disease, at a maximum. Certain signs of the metabolic syndrome, however, are more closely associated with prediabetes as defined by the ADA. These include abdominal or visceral obesity, elevated BP, elevated triglycerides, and low HDL (with or without elevated triglycerides). Diabetes is associated with an increased risk of coronary heart disease.⁶

Q. What is the relationship between prediabetes and hemoglobin A_1c (HbA_1c)?

A. There is no definitive relationship between prediabetes and elevated HbA_1c. In fact, the majority of individuals with either IFG or IGT have normal or near-normal HbA_1c values. Moreover, patients with IGT (prediabetics) often have normal random glucose levels, and their prediabetes can only be detected with an OGTT. The ADA does not recommend the use of HbA_1c as a screening test for diabetes or prediabetes.

Q. What factors put patients at risk?

A. The ADA’s expert panel does not list any specific risk factors for prediabetes itself. Prediabetes, however, is recognized as an intermediate stage of almost any disease state that could result in or lead to diabetes. An extensive list of these diseases is published in the ADA’s clinical practice guidelines (Table 1).

Q. What are the screening methods for identifying patients with prediabetes?

A. One method is to determine FBG levels. The patient refrains from eating and/or drinking for eight hours (overnight). Blood glucose is then measured using the finger-stick method. FBG levels of 100-125 mg/dL are indicative of IFG.

The second method is the OGTT. For three days prior to testing, patients must restrict their carbohydrate intake to 150-200 g/day, and they must fast the night prior to the test. On the day of the test, patients are given 75 g of glucose dissolved in 300 mL of water. Plasma glucose levels are then measured at baseline and at one and two hours. A plasma glucose level of 140-199 at two hours is indicative of IGT. Two elevated plasma glucose levels of 140-199 are required to classify a patient as having IGT.

A practical suggestion is to measure random blood glucose levels in at-risk patients anytime they are in the provider’s office or the clinic. Patients with a random blood glucose <125 can then be considered normal, while those without any symptoms of hyperglycemia and values >200 should be followed up with further testing to determine the extent of impairment in their glucose metabolism.⁷

Q. Which screening method is preferred?

A. An OGTT is the most effective way to identify individuals with impaired glucose metabolism or prediabetes. This test, however, is more involved and more expensive than determining the FBG level.⁸ Determination of FBG by the finger-stick method may prove to be a more efficient means of screening for the prediabetic state. Many patients may be unwilling to return for an FBG test.Thus, random measurements of blood glucose levels seem to be the most promising strategy for identifying prediabetics.

Q. Who should be screened?

A. There are no set guidelines for diabetes screening. The ADA, however, recommends that all people age 45 and older be screened every three years unless they are at high risk for diabetes. Risk factors are listed in Table 2. The ADA recommends more frequent testing starting at a younger age for persons at risk for diabetes.9 The frequency of testing and the age at which testing should start is ultimately based on the degree of risk and left to the clinical judgment of the individual provider. It stands to reason, however, that the higher the risk the sooner and more frequent the screening should be.

Q. Are preventive measures available?

A. The Diabetes Prevention Program (DPP) was designed to discover whether either lifestyle modifications or the use of metformin could prevent or delay the development of type 2 diabetes in patients with IGT. In this trial, 3,234 overweight adults (25 years or older, BMI Æ 24) with IGT were randomized to three groups: the lifestyle-intervention group, those taking metformin, and the placebo group.

Weight loss and a change in lifestyle resulted in a 58% reduction in incidence of type 2 diabetes. The trial results also confirmed that lifestyle modification and weight loss are more effective than metformin, which resulted in only a 31% reduction of incidence in the same population.¹⁰ Metformin increases cellular sensitivity to insulin and stimulates insulin production by the pancreas. This drug is currently used to treat diabetes and, in some cases, the dysmetabolic syndrome.

As a result of these data, preventive measures should focus on changing the patient’s lifestyle to include daily exercise and a healthy diet.¹¹ The ultimate goal of therapy should be to attain a BMI <24, optimal BP, smoking cessation, and a lipid profile within the established guidelines since prediabetics are at high risk for CAD as well as diabetes. It is advisable, therefore, to monitor the fasting lipid profile and BP of prediabetic patients. Patient education aimed at teaching better eating habits, smoking cessation, and increased daily activity are also advised.

Q. How is prediabetes treated?

A. Other studies have shown that dietary intake also plays a role in eventual onset of diabetes in high-risk individuals. A study of the dietary habits of 42,000 male health-care professionals showed that those whose diet consisted of higher amounts of whole grains, fish, poultry, fruits, and vegetables had a lower risk of developing diabetes than those with a diet of mostly red or processed meats, sweets, and high-fat dairy products. Interestingly, the increased risk for diabetes in the latter group was independent of BMI, ethnic origin, or family history for diabetes.^12,13

Although there are no direct links between IGT and/or IFG and smoking, prediabetic patients should be strongly advised to stop smoking. Smoking has been linked to an increased risk for type 2 diabetes, and this risk has been shown to be dose-dependent. Adding the link between smoking and CAD and hypertension to the latter evidence makes cessation of smoking particularly important for those who have prediabetes.^14-17

There are no large-scale studies or indications to date for use of pharmaceuticals in prediabetics. Metformin is an exception. As stated above, it was used in the DPP trial, with some success, to help reduce the incidence of diabetes in prediabetic patients. Any treatment program for prediabetic patients should focus on lifestyle modifications, including the initiation and gradual increase in daily exercise to a recommended 150 minutes per week. Patients who are reluctant to make these initial lifestyle changes should be referred for further evaluation to either an endocrinologist or cardiologist, depending on the individual’s medical history.

Dr. Aliabadi is principal investigator and associate director of the Diabetic Foot Care Program, University of South Alabama, Mobile. This article was sponsored in part by a CDC grant, No. H75/CCH422906-01.

References

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9. American Diabetes Association. Clinical Practice Recommendations. Screening for type 2 diabetes. Diabetes Care. 2004;27(Suppl 1):S11-S14.

10. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.

11. Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25:2165-2171.

12. Van Dam RM, Rimm EB, Willett WC, et al. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med. 2002;136:201-209.

13. Van Dam RM, Willett WC, Rimm EB, et al. Dietary fat and meat intake in relation to risk of type 2 diabetes in men. Diabetes Care. 2002;25:417-424.

14. Manson JE, Ajani UA, Liu S, et al. A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians. Am J Med. 2000;109:538-542.

15. Feskens EJ, Kromhout D. Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study. Am J Epidemiol. 1989;130:1101-1108.

16. Rimm EB, Chan J, Stampfer MJ, et al. Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. BMJ. 1995;310:555-559.

17. Uchimoto S, Tsumura K, Hayashi T, et al. Impact of cigarette smoking on the incidence of type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey. Diabet Med. 1999;16:951-955.