0021 -972X/78/4703-0578$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 3 Printed in U.S.A.
Hemoglobin Aic Levels in a Diabetes Detection Program* JULIO V. SANTIAGO, J. E. DAVIS, AND FRED FISHER Departments of Pediatrics, Medicine, and Pathology, Washington University School of Medicine and the Greater St. Louis Diabetes Association, St. Louis, Missouri 63110 ABSTRACT. Hemoglobin A,c concentration (HbA,L) was compared to the plasma glucose responses at 1 and 2 h of an oral glucose tolerance test (OGTT) in 63 subjects preselected because of postprandial hyperglycemia. HbA|C concentrations were correlated with 1and 2-hour plasma glucose responses during the OGTT (r = 0.776 and 0.8602, respectively). The OGTT responses were diabetic-like in 21, indeterminate in 15, and normal in 27 subjects. HbA,t values were within normal limits in all subjects who had a normal or indeterminate OGTT response and in 10 of 21 with a diabetic OGTT. The 2-h OGTT response among the 10
AMONG insulin-dependent diabetics, heJTM. moglobin Ajc concentration (HbAic) is correlated with the degree of hyperglycemia, as estimated by plasma glucose concentrations and glycosuria (1-4). HbAic has been proposed as an integrator of mean plasma glucose concentrations during the 2 months before measurement and as a tool to quantitate long term plasma glucose control in diabetics (5). The recent development of a rapid, reliable liquid chromatography technique for measurement of HbAic (6) enabled us to study its potential use in a Diabetes Detection Program which utilized a formal oral glucose tolerance test (OGTT) to diagnose diabetes mellitus. Materials and Methods The Greater St. Louis Diabetes Association tests about 10,000 subjects for diabetes mellitus every year by measuring whole blood glucose 1-3 h after a meal containing at least 100 g carbohydrate. Subjects with blood glucose concentrations of 140-210 mg/100 ml (about 10% of those tested) are invited Received January 30, 1978. Address requests for reprints to: Dr. Julio V. Santiago, Department of Pediatrics, 500 South Kingshighway, P.O. Box 14871, St. Louis, Missouri 63178. * This work was supported by NIH Grants 1-P60 AM20579 and RR-0039 and the Charles Kilo Diabetes and Vascular Research Foundation.
diabetic responders with normal HbAic was 200 ± 3 1 mg/100 ml (mean ± SD), while that of the 11 diabetic responders with elevated HbAic was 352 ± 122 mg/100 ml. All subjects with an elevated HbAit had a 2-h plasma glucose above 228 mg/100 ml, whereas only 7% of subjects with a normal HbAlL. had a 2-h glucose above this value. It is concluded that only about half of the patients currently diagnosed as having mild or chemical diabetes by OGTT have elevated HbAtc and that an elevated HbAK. is usually associated with 2-h OGTT levels above 228 mg/100 mg. (J Clin Endocrinol Metab 47: 578, 1978)
to return for a formal OGTT. They are instructed to eat a diet containing at least 300 g carbohydrate for 3 days before testing and are given a 50% dextrose solution in lemon-flavored water, followed by an equal amount of water. The quantity of dextrose is determined by the subject's height, the average subject getting about 100 g dextrose. Venous blood is drawn in the morning after a 12-h fast, and at 1 and 2 h after dextrose administration. Plasma glucose is measured with a Technicon Autoanalyzer using glucose oxidase reagents. In the fall of 1977, 63 subjects accepted an invitation for a formal OGTT. None were known to be diabetic and their average age (±1 SD) was 59.7 ± 12.0 yr. HbAic was measured in hemolysate from fluoride oxylate blood 1-4 weeks after sampling by the method of Davis et al. (6). This method has previously been shown to correlate well with the methods used by others (1-4). Among nondiabetic adults working in our laboratories (20-50 yr old) and hospitalized patients with no history of diabetes (age 40-70 yr), mean HbAlc concentrations are 6.3% and 95% of all samples are less than 8.3%. Plasma glucose OGTT responses were categorized as diabetic-like if the 1- and 2-h values exceeded 170 and 140 mg/100 ml, respectively, in subjects under 40 yr. These limits were each increased by 10 mg/decade for subjects over 40 yr. If only one of the two values were above these normal limits, the responses were categorized as indeterminate. If both values were below these limits, the responses were categorized as normal.
578
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 20:06 For personal use only. No other uses without permission. . All rights reserved.
HEMOGLOBIN Alc IN DIABETES DETECTION
Results
579
TABLE 1. OGTT glucoses in subjects with normal and elevated
Among the 63 subjects undergoing OGTT, 21 were classified as diabetic-like, 15 as indeterminate, and 27 as normal. Overall, HbAic was significantly correlated (P < 0.0001) with both the 1- and 2-h plasma glucose responses (Fig. 1). Among the subjects with normal and indeterminate OGTT responses, all had normal HbAic values. Among the 21 subjects with diabetic-like OGTT responses, 11 (53%) had elevated HbAic values (Fig. 2). Thus, all subjects with elevated HbAic had diabetic-like responses on OGTT, but 47% of subjects with diabetic-like responses had normal HbAic values.
Plasma glucose OGTT response
Subject category
OGTT re1-h Glu2-h GluHbAlc level sponse cose" cose" 1 Normal (27)6 Normal 126 ± 25 141 ± 33 2 Indeterm. (15) Normal 159 ±44 209 ± 53 Normal 200 ±31 3 Diabetic (10) 233 ± 27 Elevated 4 Diabetic (11) 345 ± 102 352 ± 122 Sixty-three subjects were divided into categories 1-4 based on their OGTT responses and HbA)c concentrations. Plasma glucose responses for each category are given on the right. a All glucose values are mean ± 1 SD. 6 Numbers in parentheses indicate number of subjects. 650 600 -
ONE HOUR y 0.0I68X + 4.15 R =0.776 16 - P< 0.0001 LOBI
z
2
TWO HOUR y = 0.0170x+3.88 R» 0.860 ' 16 - p
Vol. 47, No. 3 Printed in U.S.A.
Hemoglobin Aic Levels in a Diabetes Detection Program* JULIO V. SANTIAGO, J. E. DAVIS, AND FRED FISHER Departments of Pediatrics, Medicine, and Pathology, Washington University School of Medicine and the Greater St. Louis Diabetes Association, St. Louis, Missouri 63110 ABSTRACT. Hemoglobin A,c concentration (HbA,L) was compared to the plasma glucose responses at 1 and 2 h of an oral glucose tolerance test (OGTT) in 63 subjects preselected because of postprandial hyperglycemia. HbA|C concentrations were correlated with 1and 2-hour plasma glucose responses during the OGTT (r = 0.776 and 0.8602, respectively). The OGTT responses were diabetic-like in 21, indeterminate in 15, and normal in 27 subjects. HbA,t values were within normal limits in all subjects who had a normal or indeterminate OGTT response and in 10 of 21 with a diabetic OGTT. The 2-h OGTT response among the 10
AMONG insulin-dependent diabetics, heJTM. moglobin Ajc concentration (HbAic) is correlated with the degree of hyperglycemia, as estimated by plasma glucose concentrations and glycosuria (1-4). HbAic has been proposed as an integrator of mean plasma glucose concentrations during the 2 months before measurement and as a tool to quantitate long term plasma glucose control in diabetics (5). The recent development of a rapid, reliable liquid chromatography technique for measurement of HbAic (6) enabled us to study its potential use in a Diabetes Detection Program which utilized a formal oral glucose tolerance test (OGTT) to diagnose diabetes mellitus. Materials and Methods The Greater St. Louis Diabetes Association tests about 10,000 subjects for diabetes mellitus every year by measuring whole blood glucose 1-3 h after a meal containing at least 100 g carbohydrate. Subjects with blood glucose concentrations of 140-210 mg/100 ml (about 10% of those tested) are invited Received January 30, 1978. Address requests for reprints to: Dr. Julio V. Santiago, Department of Pediatrics, 500 South Kingshighway, P.O. Box 14871, St. Louis, Missouri 63178. * This work was supported by NIH Grants 1-P60 AM20579 and RR-0039 and the Charles Kilo Diabetes and Vascular Research Foundation.
diabetic responders with normal HbAic was 200 ± 3 1 mg/100 ml (mean ± SD), while that of the 11 diabetic responders with elevated HbAic was 352 ± 122 mg/100 ml. All subjects with an elevated HbAit had a 2-h plasma glucose above 228 mg/100 ml, whereas only 7% of subjects with a normal HbAlL. had a 2-h glucose above this value. It is concluded that only about half of the patients currently diagnosed as having mild or chemical diabetes by OGTT have elevated HbAtc and that an elevated HbAK. is usually associated with 2-h OGTT levels above 228 mg/100 mg. (J Clin Endocrinol Metab 47: 578, 1978)
to return for a formal OGTT. They are instructed to eat a diet containing at least 300 g carbohydrate for 3 days before testing and are given a 50% dextrose solution in lemon-flavored water, followed by an equal amount of water. The quantity of dextrose is determined by the subject's height, the average subject getting about 100 g dextrose. Venous blood is drawn in the morning after a 12-h fast, and at 1 and 2 h after dextrose administration. Plasma glucose is measured with a Technicon Autoanalyzer using glucose oxidase reagents. In the fall of 1977, 63 subjects accepted an invitation for a formal OGTT. None were known to be diabetic and their average age (±1 SD) was 59.7 ± 12.0 yr. HbAic was measured in hemolysate from fluoride oxylate blood 1-4 weeks after sampling by the method of Davis et al. (6). This method has previously been shown to correlate well with the methods used by others (1-4). Among nondiabetic adults working in our laboratories (20-50 yr old) and hospitalized patients with no history of diabetes (age 40-70 yr), mean HbAlc concentrations are 6.3% and 95% of all samples are less than 8.3%. Plasma glucose OGTT responses were categorized as diabetic-like if the 1- and 2-h values exceeded 170 and 140 mg/100 ml, respectively, in subjects under 40 yr. These limits were each increased by 10 mg/decade for subjects over 40 yr. If only one of the two values were above these normal limits, the responses were categorized as indeterminate. If both values were below these limits, the responses were categorized as normal.
578
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 20:06 For personal use only. No other uses without permission. . All rights reserved.
HEMOGLOBIN Alc IN DIABETES DETECTION
Results
579
TABLE 1. OGTT glucoses in subjects with normal and elevated
Among the 63 subjects undergoing OGTT, 21 were classified as diabetic-like, 15 as indeterminate, and 27 as normal. Overall, HbAic was significantly correlated (P < 0.0001) with both the 1- and 2-h plasma glucose responses (Fig. 1). Among the subjects with normal and indeterminate OGTT responses, all had normal HbAic values. Among the 21 subjects with diabetic-like OGTT responses, 11 (53%) had elevated HbAic values (Fig. 2). Thus, all subjects with elevated HbAic had diabetic-like responses on OGTT, but 47% of subjects with diabetic-like responses had normal HbAic values.
Plasma glucose OGTT response
Subject category
OGTT re1-h Glu2-h GluHbAlc level sponse cose" cose" 1 Normal (27)6 Normal 126 ± 25 141 ± 33 2 Indeterm. (15) Normal 159 ±44 209 ± 53 Normal 200 ±31 3 Diabetic (10) 233 ± 27 Elevated 4 Diabetic (11) 345 ± 102 352 ± 122 Sixty-three subjects were divided into categories 1-4 based on their OGTT responses and HbA)c concentrations. Plasma glucose responses for each category are given on the right. a All glucose values are mean ± 1 SD. 6 Numbers in parentheses indicate number of subjects. 650 600 -
ONE HOUR y 0.0I68X + 4.15 R =0.776 16 - P< 0.0001 LOBI
z
2
TWO HOUR y = 0.0170x+3.88 R» 0.860 ' 16 - p
