Health & Medical Endocrine disease

Ask the Experts - Follow-up Testing of Patient With Impaired Fasting...

´╗┐Ask the Experts - Follow-up Testing of Patient With Impaired Fasting...
A 35-year-old man, newly diagnosed with impaired fasting glucose (120 mg/dL) and also with a strong family history of type 2 diabetes (both parents have type 2 diabetes) came to consult us about doing the 2-hour oral glucose tolerance test (OGTT). Is this test necessary, or can one rely on the existing evidence and simply advise him to enter a diet, exercise, and medical follow-up program?

Loakim Tsigeridis, MD



Until very recently, the physician asking the question would have been correct in thinking that the "existing evidence" suggests the patient should "diet, exercise, and [have a] medical follow-up." We now have intriguing information suggesting that a more aggressive policy may be appropriate, and that it may be worthwhile to perform a glucose-tolerance test (GTT).

Does the patient actually have diabetes or impaired glucose tolerance (IGT)?

Information from the National Health and Nutrition Examination Survey shows that at least among individuals over age 60, about one half of newly diagnosed patients with diabetes have a fasting glucose of less than 126 but a 2-hour glucose over 200 mg/dL. Similarly, the Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) studied data from 13 European centers with 25,364 persons, of whom 1275 had prior diagnosis of diabetes. Diabetes was present based on a fasting glucose > 126 mg/dL alone in 654 patients, a 2-hour glucose > 200 mg/dL alone in 522, and by both criteria in 489 patients (Table 1). Thus, the patient described in the question has a substantial chance (between 20% and 50%) of having diabetes rather than IGT.


2-hour Glucose (mg/dL)*

<140

140-200

>200

Total

Fasting Glucose (mg/dL)*




<100
21,968

2562

316

24,846

100-125

2020

893

206

3119

>125

276

378

489

1143

Total

24,264

3833

1011

29,108


* Whole blood

What is the significance of the 2-hour glucose level?

An important concern would be whether one can predict an increase in adverse outcome among individuals based on the degree of hyperglycemia. The DECODE study analyzed mortality at 10-year follow-up. To look specifically at the individual in question, the risk of adverse outcomes among patients in this study with fasting glucose between 110 and 125 mg/dL was strongly associated with 2-hour glucose level. Their mortality increased from 15, to 19, to 24 deaths per 1000 person-years with 2-hour glucose values of < 140, 140-200, and > 200 mg/dL (Table 2).

Table 2. Mortality/1000 Person-Years in the DECODE Study


2-hour Glucose (mg/dL)*

<140

140-200

>200

Fasting Glucose (mg/dL)*



<100
12.7

19.9

25.9

100-125

15.0

19.4

22.6

>125

20.5

22.3

39.0


* Whole blood

Indeed, within each fasting glucose level, mortality increased with 2-hour glucose value, whereas only for those with normal 2-hour glucose levels was an increase in mortality directly correlated to increasing fasting glucose.

Multivariate analysis revealed that adjusting the fasting glucose for the 2-hour glucose eliminated the ability of the former to independently predict mortality, whereas adjusting the 2-hour glucose for the fasting glucose level did not eliminate the direct relationship between the 2-hour glucose level and mortality. The data suggest that reduction of 2-hour glucose by about 35 mg/dL would decrease deaths by 28.8% in those with 2-hour glucose levels > 200 mg/dL, and by 20.5% in those with 2-hour levels > 140 mg/dL. Similar analyses have been reported from Pacific Island population studies with isolated postchallenge hyperglycemia predicting mortality almost as well as known diabetes.

Do we have an effective approach to treating glycemia in patients identified as having diabetes based on either fasting or 2-hour postchallenge glucose levels?

This is a crucial question. Studies suggest that diet and exercise interventions in such persons can decrease the risk of diabetes. The Diabetes Prevention Project (DPP) is studying hyperglycemic patients in the "upper half" of IGT range, to see if identifying patients prior to the onset of disease can prevent diabetes and its complications such as cardiovascular disease (CVD). More than 3000 persons have been randomized to metformin, to intensive diet and exercise, or to a control group. Interventions that can be directed specifically at postload hyperglycemia are the rapid-acting insulin secretagogues nateglinide and repaglinide. When nateglinide is given at a dose of 120 mg 3 times daily before meals to individuals with fasting glucose averaging 200 mg/dL, there is a fall in postprandial glucose without change in overnight or fasting levels, suggesting that this may prove an effective treatment. Studies with this agent in patients with IGT are being planned.

More aggressive CVD-risk factor treatment offers another rationale for early diagnosis of diabetes. There is convincing evidence that the risk of cardiovascular events in patients with diabetes and without a history of CVD is similar to that in patients with cardiovascular disease and without a history of diabetes.[8] Thus, by performing a GTT it may be possible to determine whether the patient in the question, for example, should either be given lipid treatment to bring the LDL cholesterol to < 100 mg/dL, or should be started on an angiotensin converting enzyme (ACE) inhibitor without having hypertension if there are other risk factors.[9]

Thus, the potential use of the GTT for assessment of glycemic and cardiovascular risk status for individuals such as the one described suggests that this test may become more frequently used. The administration of a 75-g oral glucose load with measurement of the fasting and 2-hour glucose level is sufficient. Additional blood samples, which add to the difficulty of using the test in clinical practice, need not be obtained.

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