Epidemiology

Studies in the United Kingdom have reported the prevalence of impaired glucose tolerance in the 35-65 year age group to be about 17%.⁴

Risk factors

• Obesity
• First-degree relative with diabetes
• Certain ethnic groups, e.g. Asian, Afro-Caribbean⁵
• Hypertension⁶

Presentation

• Patients with impaired glucose tolerance are usually asymptomatic.
• Features of related risk factors for cardiovascular disease may be present, even with a mild degree of hyperglycemia. They include hypertension, obesity, dyslipidaemia, and macrovascular disease, such as stroke, coronary disease or peripheral vascular disease.

Investigations

Oral glucose tolerance test:

• Overnight fast of 8-14 hours; only water may be drunk. Smoking should also be avoided during this time.
• Adults: drink 75 g anhydrous glucose dissolved in 250-300 ml water over 5 minutes. For children, the glucose load is 1.75 g per kg body weight.
• Blood glucose is measured before the drink and after 30, 60, 90 and 120 minutes.

Associated diseases

• Several cardiovascular findings are more prevalent, including hypertension, raised serum cholesterol, angina, abnormal heart findings and medical history of arteriosclerosis and stroke.⁷
• Impaired fasting glycaemia is defined as a fasting plasma glucose of 6.1 mmol/l or greater but less than 7.0 mmol/l. There is an increased risk of development of diabetes but less evidence of an associated risk of cardiovascular disease.

Management

• Increasing evidence indicates that intervention can favourably influence the clinical course of impaired glucose tolerance, with some studies showing a 58% reduction in progression to diabetes.⁸
• The metabolic syndrome (defined by impaired fasting glucose, large waist circumference, and high triglycerides) efficiently identifies subjects likely to have impaired glucose tolerance on oral glucose tolerance test, and thus be appropriate for diabetes prevention interventions.⁹
• Annual screening of people with impaired glucose tolerance by fasting blood glucose is currently recommended.

General measures

• It has been shown that the risk of progression from impaired glucose tolerance to type 2 diabetes mellitus can be reduced by lifestyle interventions.¹⁰
• The advice is essentially the same as diet and exercise advice in diabetes:
  • Weight reduction, if appropriate
  • Reduction in total intake of fat and intake of saturated fat
  • Increasing intake of dietary fibre
  • Increasing physical activity

Pharmacological

• Reversal of drug-related iatrogenic causation of glucose intolerance. Whenever possible, substitute agent(s) that do not have an adverse effect on glucose tolerance, or reduce the dosage of the offending drug, e.g. replacing a thiazide diuretic when treating hypertension, minimising use of corticosteroids.
• Several clinical trials have found that lifestyle modification is the most effective strategy to prevent progression to type 2 diabetes.¹¹ Both metformin and acarbose have been demonstrated to decrease the development of type 2 diabetes.
• Ongoing clinical trials are evaluating other agents, including ACE inhibitors, angiotensin receptor antagonists and thiazolidinediones, to prevent both type 2 diabetes and cardiovascular events. In combination with lifestyle modification, these therapies may provide effective prevention of type 2 diabetes and its consequences in high-risk patients.¹²
• There has been some showing that ACE inhibitors may have a role in preventing diabetes in individuals with high cardiovascular risk factors.¹³

Complications

• 20-50% of people with impaired glucose tolerance will progress to type 2 diabetes within 10 years of diagnosis.¹⁴
• In addition, people with impaired glucose tolerance are known to be at significantly increased risk of cardiovascular disease, which may present before the onset of diabetes. Rates of cardiovascular risk factors are intermediate between those with normal glucose tolerance and those with diabetes. Impaired fasting glycaemia has not been shown to be a risk factor for cardiovascular disease.¹⁵
• Baseline plasma glucose is the most consistent predictor of progression to diabetes.
• Impaired glucose tolerance has not been clearly associated with microvascular complications e.g. nephropathy, retinopathy or neuropathy.

Prevention

• Avoid being overweight and eat a healthy diet, with high fibre, low fat and lots of fruit and vegetables.
• Encourage regular physical activity.
• Avoid alcohol abuse.

Document references

1. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, World Health Organization/International Diabetes Federation, 2006
2. Zavaroni I, Dall'Aglio E, Bonora E, et al; Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance. Am J Med. 1987 Oct;83(4):609-12. [abstract]
3. No authors listed, JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart. 2005 Dec;91 Suppl 5:v1-52.
4. Davies MJ, Gray IP; Impaired glucose tolerance. BMJ. 1996 Feb 3;312(7026):264-5.
5. Whincup PH, Gilg JA, Papacosta O, et al; Early evidence of ethnic differences in cardiovascular risk: cross sectional comparison of British South Asian and white children. BMJ. 2002 Mar 16;324(7338):635. [abstract]
6. No authors listed; Hypertension, insulin, and proinsulin in participants with impaired glucose tolerance. Hypertension. 2002 Nov;40(5):679-86. [abstract]
7. Harris MI; Impaired glucose tolerance in the U.S. population. Diabetes Care. 1989 Jul-Aug;12(7):464-74. [abstract]
8. Tuomilehto J, Lindstrom J, Eriksson JG, et al; Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. [abstract]
9. Meigs JB, Williams K, Sullivan LM, et al; Using metabolic syndrome traits for efficient detection of impaired glucose tolerance. Diabetes Care. 2004 Jun;27(6):1417-26. [abstract]
10. Mensink M, Blaak EE, Corpeleijn E, et al; Lifestyle intervention according to general recommendations improves glucose tolerance. Obes Res. 2003 Dec;11(12):1588-96. [abstract]
11. Ratner R, Goldberg R, Haffner S, et al; Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care. 2005 Apr;28(4):888-94. [abstract]
12. Petersen JL, McGuire DK; Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management. Diab Vasc Dis Res. 2005 Feb;2(1):9-15. [abstract]
13. Yusuf S, Gerstein H, Hoogwerf B, et al; Ramipril and the development of diabetes. JAMA. 2001 Oct 17;286(15):1882-5. [abstract]
14. Alberti KG; Impaired glucose tolerance: what are the clinical implications? Diabetes Res Clin Pract. 1998 Jul;40 Suppl:S3-8. [abstract]
15. Tominaga M, Eguchi H, Manaka H, et al; Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999 Jun;22(6):920-4. [abstract]

Internet and further reading

• Olatunbosun ST, Dagogo-Jack S; Glucose Intolerance, e-Medicine, Aug 2008

Acknowledgements