The diagnosis of diabetes is made by demonstrating abnormally increased blood glucose values under certain controlled conditions. If insulin deficiency is small, abnormality is noted only when an unusually heavy carbohydrate load is placed on the system. In uncompensated insulin deficiency, fasting glucose is abnormal; in compensated insulin deficiency, a variety of carbohydrate tolerance test procedures are available to unmask the defect. To use and interpret these procedures, one must thoroughly understand the various factors involved.

Glucose tolerance tests (GTTs) are provocative tests in which a relatively large dose of glucose challenges the body homeostatic mechanisms. If all other variables are normal, it is assumed that the subsequent rise and fall of the blood glucose is due mainly to production of insulin in response to hyperglycemia and that the degree of insulin response is mirrored in the behavior of the blood glucose. Failure to realize that this assumption is predicated on all other variables being normal explains a good deal of the confusion that exists in the literature and in clinical practice.

Test standardization

The most important factor in the GTT is the need for careful standardization of the test procedure. Without these precautions any type of GTT yields such varied results that an abnormal response cannot be interpreted. Previous carbohydrate intake is very important. If diet has been low in both calories and carbohydrates for as little as 3 days preceding the test, glucose tolerance may be diminished temporarily and the GTT may shift more or less toward diabetic levels. This has been especially true in starvation, but the situation does not have to be this extreme. Even a normal caloric diet that is low in carbohydrates may influence the GTT response. A preparatory diet has been recommended that includes approximately 300 gm of carbohydrates/day for 3 days preceding the test, although others believe that 100 gm for each of the 3 days is sufficient. The average American diet contains approximately 100-150 gm of carbohydrates; it is obviously necessary in any case to be certain that the patient actually eats at least 100 gm/day for 3 days.

Factors that affect the glucose tolerance test

Inactivity has been reported to have a significant influence on the GTT toward the diabetic side. One study found almost 50% more diabetic GTT responses in bedridden patients compared with ambulatory patients identical in most other respects. The effect of obesity is somewhat controversial. Some believe that obesity per se has little influence on the GTT. Others believe that obesity decreases carbohydrate tolerance; they have found significant differences after weight reduction, at least in obese mild diabetics. Fever tends to produce a diabetic-type GTT response; this is true regardless of the cause but more so with infections. Diurnal variation in glucose tolerance has been reported, with significantly decreased carbohydrate tolerance during the afternoon in many persons whose GTT curves were normal in the morning. This suggests that tests for diabetes should be done in the morning. Stress, when severe, results in release of various hormones (e.g., epinephrine and possibly cortisol and glucagon), which results in decreased glucose tolerance. Acute myocardial infarction, trauma, burns, and similar conditions frequently are associated with transient postprandial hyperglycemia and occasionally with mild fasting hyperglycemia. This effect may persist for some time. It has been recommended that definitive laboratory testing for diagnosis of diabetes be postponed for at least 6 weeks. However, if the fasting blood glucose (FBG) level is considerably elevated and there is substantial clinical evidence of diabetes, the diagnosis can be made without additional delay.

There is a well-recognized trend toward a decreasing carbohydrate tolerance with advanced age. For each decade after age 30, fasting glucose increases 1-2 mg/100 ml (0.05-0.10 mmol/L) and the 2-hour value increases 8-20 mg/100 ml (0.4-1.1 mmol/L). There are three schools of thought as to the interpretation of this fact. One group believes that effects of aging either unmask latent diabetes or represent true diabetes due to impairment of islet cell function in a manner analogous to subclinical renal function decrease through arteriosclerosis. Another group applies arbitrary correction formulas to decrease the number of abnormalities to a predetermined figure based on estimates of diabetes incidence in the given population. A third group, representing the most widely accepted viewpoint, regards these changes as physiologic rather than pathologic. To avoid labeling many elderly persons diabetic who have no other evidence of diabetes, some experts deliberately extend the upper limits of the oral GTT reference range. The National Diabetes Data Group (NDDG) diabetes criteria (discussed later) incorporate some of this shift of the reference range.

The question arises occasionally as to what serum glucose values are normal when a patient is receiving intravenous 5% dextrose. In 20 patients at our hospital who had no evidence of disease known to affect serum glucose, values ranged from 86-232 mg/100 ml (4.74-12.78 mmol/L), with a mean value of 144 mg/100 ml (8.0 mmol/L). Only one patient exceeded 186 mg/100 ml (103 mmol/L).