| Carbohydrate Metabolism: The Glucose-Insulin Homeostatic System |
| Tests to evaluate the glucose-insulin homeostatic system were given during the following periods: |
- Intravenous glucose tolerance test (IVGTT), January 1963-June 1977.
- Intravenous insulin tolerance test (IVITT), June 1963-June 1964.
- Cortisone glucose tolerance test (CGTT), January 1964-June 1977.
- Oral glucose tolerance test (OGTT), 1.75 g/kg body weight, July 1964-June l977;
since June 1977 the glucose dose has been 40 g/m2 surface area.
- Intravenous tolbutamide response test (TRT), January 1965-June 1977.
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| One of the tests is usually performed on each visit. The four tests that were administered until June 1977 were generally given in a series that was repeated after all four had been administered. Since that date only the OGTT has been done. All are performed under basal conditions. |
| Activity prior to the test is limited, since subjects spend the preceding night at the Center as part of their 2½-day stay. Subjects remain in bed, in a reclining or a semi-reclining position, during the test. Smoking is not permitted before or during the test. Fasting and all subsequent venous-blood samples are obtained through an indwelling catheter. |
| Glucose was determined by a manual glucose oxidase method until September 1963; by the AutoAnalyzer automated ferricyanide reduction method (Technicon Instruments Corp., Tarrytown, New York) until June 1977; and thereafter by an automated glucose oxidase method (Beckman Instruments, Inc., Fullerton, California). Initially, from 1963 to 1966, whole-blood samples were deproteinized by the Somogyi technique (1945). Since 1966, plasma samples have been analyzed without deproteinization. Factors for conversion from the manual glucose oxidase to the automated ferricyanide method and from whole-blood to plasma samples were determined by simultaneous analyses of multiple specimens by the older and the newer methods. Since the AutoAnalyzer and Beckman methods gave nearly identical results, it was not necessary to apply a conversion factor. |
| The tests have been performed as follows: |
| Intravenous glucose tolerance test (IVGTT). A 20% solution of dextrose in water (0.375 g/kg body weight) was infused at a constant rate over a five-minute period. Blood samples were collected every ten minutes until 60 minutes; in the earliest studies, a final sample was collected at 80 minutes. |
| Intravenous insulin tolerance test (IVITT). A dose of 0.05 units of crystalline zinc insulin per kg body weight was injected nearly instantaneously. Venous-blood samples were collected from an indwelling catheter at ten-minute intervals for one hour. |
| Cortisone glucose tolerance test (CGTT). Cortisone acetate was given by mouth 8.5 and two hours before glucose ingestion, in two equal doses determined by body weight (< 124 lb = 37.5 mg; 124-159 lb = 50 mg; 160-194 lb = 62.5 mg; 195-230 lb = 75 mg; and > 230 lb = 87.5 mg). The glucose dose was 1.75 g/kg actual (as opposed to "desirable") body weight, given as a 30% solution flavored with lemon juice, which was ingested in ten minutes or less. Blood samples were drawn every 20 minutes for two hours (Pozefsky et al., 1965). |
| Oral glucose tolerance test (OGTT). The technique was originally the same as that used for the CGTT, but the steroid administration was omitted. In July 1977 the glucose dose was changed to 40 g/m2 surface area, in accordance with the recommendation of the Committee on Statistics of the American Diabetes Association (Klimt et al., 1969). |
| In 1979 the National Diabetes Data Group recommended that 75g of glucose be given to all subjects regardless of body size. This dose is equivalent to 40 g/m2 surface area for an average-sized person. We have elected to continue use of the 40 g/m2 dosage which the Data Group had rejected as impractical for the usual clinical test situations. Considering a dose adjustment for body size an advantageous detail, we decided not to introduce still another technical change into our study. |
| Intravenous tolbutamide response test (TRT). One gram of sodium tolbutamide in a 5% solution per 70 kg body weight was injected through an indwelling intravenous catheter in two minutes. Zero time was taken as the midpoint of the injection. Blood samples were obtained at 2, 6, 10, 15, 20, 30, 45, and 60 minutes. |
| Performance was judged primarily by the percentage of fall in glucose concentration at 20 and 30 minutes (Swerdloff et al., 1967). |
| Glucose-clamp test. A manual feedback technique, the glucose clamp, makes it possible to maintain blood glucose at any level chosen by the investigator (Andres et al., 1966; DeFronzo et al, 1979). Two basic types of study have been performed. In the "euglycemic clamp study," insulin is infused at a constant rate while the blood-glucose concentration is maintained at the subject's basal level. This is primarily a test of sensitivity of body tissues to insulin. In the "hyperglycemic clamp study," the plasma-glucose concentration is raised rapidly to a hyperglycemic plateau and is maintained at that level for two hours. The glucose plateaus studied have been 54, 98, 143, or 231 mg/dl above the basal level. This is a test of pancreatic beta-cell sensitivity to glucose and sensitivity of body tissues to insulin. These tests were given to subjects selected for special characteristics with respect to glucose tolerance and obesity. The schedule for retesting has not yet been determined. |
