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Investigation of the effect of poorly controlled diabetes mellitus on erythrocyte life
Investigation of the Effect of Poorly Controlled Diabetes Mellitus on Erythrocyte Life Sabri Sayinalp Tiimay S&en Aydan Usman Semra Diindar
-
ABSTRACT Erythrocyte half-life (E, _ x,3 has been measured in 11 patients with poorly controlled blood sugar levels and compared with a normal control group to determine whether decreased red cell deformability, which occurs in diabetic patients, causes shortening of erythrocyte life or not. No difference was seen (EtT112 = 28.1 days in diabetic
INTRODUCTION
I
t has been reported that erythrocyte deformability decreases in diabetes mellitus . *-4This phenomenon can be expected to cause shortening of erythrocyte life. For this reason, erythrocyte half-life (Et-~/z) was determined in a group of diabetic patients with elevated blood sugar levels, compared with a normal control group, and the effect of poorly controlled diabetes mellitus upon erythrocyte life was investigated. MATERIAL
AND METHODS
Eleven patients with poorly controlled diabetes, determined by measuring fasting plasma glucose and I-IbA, levels (glucose > 7.8 mmol/L, HbAl > 8.6%), entered the study. Physical signs of these patients were normal. They had no history of chronic obstructive lung disease. Their lung radiographs and hemoglobin levels were normal (between 14-18 g/dL for men and 12-14 g/dL for women). They were using no drugs
Department of Internal Medicine, Hacettepe University, School of Medicine, Ankara, Turkey Reprint requests to be sent to: Dr. Sabri SayinaIp, Bahcelievler Sondurak, Eser Sitesi B-3/10 06490, Ankara, Turkey. journal of Diabetes and Its Complications 7995; 9:190-193 0 Elsevier Science Inc., 1995 655 Avenue of the Americas, New York, NY 10010
patients and 28.5 days in controls). There was also no correlation between E+1,2 and glycosylated hemoglobin (HbAI) levels. It has been concluded that poorly controlled diabetes mellitus has no effect upon erythrocyte life. (Journal of Diabete patients and Its Complications 9;3:190-193, 1995.)
except insulin or oral antidiabetics. Control group consisted of seven healthy volunteers without anemia or diabetes mellitus and matched the patient group by age (general information about patient and control groups can be seen in Table 1). Informed consent was given by all subjects. HbAl determinations were made by liquid chromatography method by using the kits produced by Sigma Diagnostics, Inc. Coefficient of variation for the assay was 0.9%. For plasma glucose determinations, A&a-B automated stat/routine analyzer was used. Hemoglobin determinations were made by model S-plus VI coulter counter produced by Coulter Electronics Inc. EtWli2 was measured by Chromium 51 Labelling.5,6 Samples (40-50 mL) of the subjects’ blood were collected in a bottle containing 10 mL acid-citrate-dextrose (ACD) solution; 75-100 clCi of high specific activity 51Cr-sodium chromate was added and incubated at room temperature for 30 min with gentle mixing; 100 mg ascorbic acid was added to the labeling vial at the end of the incubation period to reduce the unbound chromate to chromic, thereby preventing further labeling of erythrocytes by 51Cr. The whole of the blood was injected. Blood samples were obtained at 24, 36, 48 h and every day for 2 weeks. The normal elution rate was accepted to be 1.0% in both group. All sam-
SSDI
1056-8727/95/$9.50 1056-8727(94)00041-N
J Diab Comp
1995; 9:190-193
ERYTHROCYTE
TABLE 1. GENERAL INFORMATIONS ABOUT PATIENTS AND CONTROL GROUP Patients
Age (years) Mean f SD Range Sex Men Women Diabetes type NIDDM IDDM Diabetes duration (years) Mean * SD Range Hh (&-IL) Men (mean f SD) Women (mean + SD) Fasting plasma glucose (mmol/L) Mean f SD Range
Controls
53.0 f 11.7 32-70
45.7 f 11.9 31-65
3 8
4 3
LIFE
10.2 f 4.3 6-20 14.5 + 0.6 13.4 f 0.6
15.1 f 0.5 13.7 f 0.3
13.8 f 3.6 8.2-19.6
4.8 f 0.6 3.8-5.8
SD, standard deviation; IDDM, insulin-dependent diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; HB, Hemoglobin
ples were counted in a well counter and counts were plotted on semilog paper as a function of time. For statistical evaluations, Mann-Whitney U test, and Pearson product moment correlation analyses were used. RESULTS
HbAl levels were 13.9% f 2.8% in diabetic patients and 6.1% f 1.8% in controls; the difference was significant statistically (p < 0.05). Ete112was measured as 28.1 f 3.5 days in diabetic patients and 28.5 f 3.2 days in control group, there was no statistically significant difference (Table 2); and there was no correlation between I-IbAl levels and Et-r12 in diabetic patients (Y = 0.16, t = 0.49, Figure 1). One value with an erythrocyte half-life of 35 days and an HbAr level of 20% could be viewed as an outlier. But when this value was excluded, there was also no correlation between HbAl and erythrocyte half-life. DISCUSSION
Nonenzymatic glycosylation of proteins is an event that occurs in diabetics proportionally to hyperglycemia and which is claimed that it is related with chronic complications of diabetes. 7,8Hemoglobin is one of the glycosylated proteins and I-IbAl determinations are being used as an index to show long-term glycemic control.g It has been demonstrated that I-IbAl level in-
POORLY
CONTROLLED
DM
191
TABLE 2. THE COMPARISON OF PATIENT AND CONTROL GROUPS ACCORDING TO ERYTHROCYTE HALF-LIFE AND HbA, LEVELS Patients
Controls
FIbAl
13.9 f 2.8
Et-m (days)
(9.0-20.0) 28.1 f 3.5 (23.0-35.0)
6.1 f 1.8 (2.0-7.5) 28.5 f 3.2 (25.0-36.0)
HbAz,
glycosyhted
hemoglobin;
Results are expressed
7 4
AND
Et- 112, erythrocyte
P value p < 0.05
NS
half-life.
as mean f SD (range).
creases as correlated with erythrocyte age,lOJ1 and it can be used as an index of erythrocyte life in normoglycemic individuals. Accordingly, it has been seen that the levels of glycosylated hemoglobin fall in hemolytic anemias,12*13 and it is claimed that, in iron deficiency anemia, it increases in period of decreased erythrocyte production and decreases during treatment because of increasing of young erythrocyte.‘* The ability of the erythrocyte to change its shape in response to an applied force has been termed as erythrocyte deformability.*5 It is an important physiological factor that plays an essential part in the delivery of oxygen to the tissues. l6 It has been demonstrated that erythrocyte deformability decreases in diabetic patients,*-4,16 and experiments with hyperglycemic mouse erythrocytes have yielded similar resu1ts.l’ It has been claimed that two mechanisms could play a role in this event: (1) loss of elasticity due to erythrocyte membrane glycosylation and changes in lipid fraction, and (2) increasing of cytoplasmic viscosity because of glycosylation of hemoglobin.2-4 It can be expected that a decrease in erythrocyte deformability
36 34
0 0
32 . . Et112 (days)
OO
30 -28 a26 .-
0
24 a.
0
0
0
0
22 -20 J 8
I 10
12
14
16
18
20
22
HbAl(%)
FIGURE 1 The demonstration of erythrocyte half-life (E,-& values in diabetic patients according to glycosylated hemoglobin (HbAI) levels (r = 0.16, t = 0.49; no correlation was found).
192
SAYINALP
ET AL.
can cause shortening of erythrocyte life. To investigate this, we determined Et-l,2 in 11 patients with poorly controlled diabetes and compared them with the control group; we didn’t find any difference. Being expected that glycosylated hemoglobin reduces erythrocyte deformability by augmenting cytoplasmic viscosity, the relation between HbAl levels and Et-,,2 was investigated, but no correlation was found. There is only one report’* on this issue in the literature and, in some textbooks, as referenced with that study, it has been said that erythrocyte life reduces 15% in diabetic patients. In that study, made by Peterson et al., E,. II? had been measured in seven diabetic patients before and after blood sugar control. Results determined that it increased from 27 days to 31 days; a 15% increase had been seen with blood sugar control; however, this difference is not important statistically as the number of patients are few and there is not a normal control group. Thus, the results are not sufficient to lead to a precise conclusion. The design and the results of our study are somewhat different from those of Peterson et al., and they point out that erythrocyte life isn’t reduced in diabetic patients. Some hypotheses can be proposed to explain this result despite reduced erythrocyte deformability in diabetes mellitus . A first hypothesis is that, although hyperglycemia reduces erythrocyte deformability, it can make some changes that increase the resistance by affecting erythrocyte metabolism. For example, glycosylation of hemoglobin can result in an increase of oxygen affinity by reducing the binding with 2,3 diphosphoglycerate.19 In this situation, the amount of free 2,3 DPG increases, and, by the inhibition of the enzyme diphosphoglyceromutase, 3-phosphoglycerate is produced from 1,3 diphosphoglycerate directly.” This change in the direction of the chemical reaction can result in an increase of ATP formation. It can be expected that the increasing ATP level can augment erythrocyte resistance. A second hypothesis is that, although hyperglycemia reduces erythrocyte deformability, it can effect the erythrocyte degradation environment in the opposite direction. It has been suggested that the hypoglycemic environment that occurs in the spleen can play a role in erythrocyte degradation.21 The increase in blood sugar, by preventing hypoglycemia in the spleen, can prevent erythrocyte degradation. CONCLUSION In this study it has been demonstrated that erythrocyte life doesn’t change in patients with poorly controlled diabetes. Some new studies will be useful to explain erythrocyte life not changing despite reduced erythrocyte deformability in diabetes mellitus.
\ Diuh Camp 1995; 9:190-19.3
REFERENCES 1. Schmid-Schonbein H, Volger E: Red-cell aggregation and red-cell deformability in diabetes. Diabetes 25(suppl.
2):897-902, 1976. 2. McMillan
DE, Utterback NG, Puma JL: Reduced erythrocyte deformability in diabetes. Diabetes 27:895-901,
1978. 3. KiesewetterH,
JungF, Kiirber N, Wolf S, Kiehl R, Frank M, Reim M, Sitzmann FC: Microcirculation and hemorheology of children with type I diabetes. Klin Wochenschr 64:962-968, 1986.
4. Garnier
M, Attali JR, Valensi I’, Delatour-Hanss E, Gaudey F, Koutsouris D: Erythrocyte deformability in diabetes and erythrocyte membrane lipid composition. Metabolism 39:794-798, 1990.
5.
Gray SJ, Sterling K: The tagging of the red cells and plasma proteins with radioactive chromium. 1 Clin Invest 29:1604-1613, 1950.
6.
Read RC: Studies of red-cell volume and turnover radiochromium. N En@] Med 250:1021, 1954.
7. Kennedy L, Lyons TJ: Non-enzymatic Med Bull 45:174-190, 1989.
using
glycosylation.
Br
8. Kennedy L, Baynes JW: Non-enzymatic glycosylation and the chronic complications of diabetes: an overview. Diabetologia 26:93-98, 1984.
9. National committee
Diabetes Data Group: Report on glucosylated haemoglobin.
of the expert Diabetes Care
7602-606, 1984. 10.
Cordera R, Andraghetti G, Bonadonna R, Gherzi R, Marie110 M, Odetti P, Visiani G, Berri F, Adezati L: Influence of cell age and ketoaminic linkage on rapid glycosylation of hemoglobin in human red cells in vitro. Horn Metab Res 17:201-204, 1985.
11.
Elseweidy MM, Stallings M, Abraham EC: Changes in glycosylated hemoglobins with red cell aging in normal and diabetic subjects and in newborn infants of normal and diabetic mothers. 1 Lab Clin Med 102:628-636, 1983.
12.
Rigal D, Monestier M, Baboin-Joubert M, Chabauda Sassoulas D, Marseglia G, Ville D, Meyer F, Jouvenceau A: Appreciation de la duree de vie des globules rouges par le dosage de l’hemoglobine glycosylee. Presse Med
14:521-523,1985. 13.
Krauss SJ, Hahn DA, Harper D, Shell S, Baisden CR: The affinity glycated hemoglobin in a family with hereditary sypherocytosis and in other non-hemoglobinopathic hemolytic anemias. Ann Cli Lab Sci 17(5):331-
338, 1987. 14. Sluiter WJ, VanEssen Glycosylated
IH, Reistma WD, Doorenbos H: hemoglobin and iron deficiency. Lancet
531-532, 1980. 15. Sumihare N, Taniguchi erythrocte
deformability.
S, Kon H: An EPR study on Prog Biophys Molec Biol55:85-
105, 1991. 16. Mokken FC, Kedaria
M, Henny CP, Hardeman MR, Gelb AW: The clinical importance of erythrocyte deformability, a hemorrheological parameter. Ann Hemato1 64:113-z!, 1992.
17. Engstrom
KG, Grankvist K, Taljedal IB: Insulin-driven erythropoiesis may underlie impairment of erythrocyte
J Diab Camp
1995; 9:190-193
deformability in hyperinsulinaemic, hyperglycaemic oblob mice. Diubetologia 33:127-130, 1990. 18. Peterson CM, Jones KL, Koenig RJ, Melvin ET, Lehrman ML: Reversible hematologic sequelae of diabetes mellitus. Ann Intern Med 86:425-429, 1977. 19. Bunn HF, Briehl RW: The interaction of 2,3-diphospho-
ERYTHROCYTE
LIFE
AND
POORLY
CONTROLLED
DM
1%
glycerate with various human hemoglobins. J Clin lnvest 49:1088-1095, 1970. 20. Williams JW: Hematology, 4th edition. McGraw-Hill, 1990. 21. Jandle JH, Aster RI-I: Increased splenic pooling and the pathogenesis of hypersplenism. Am J Med Sci 253:383, 1967.
-
ABSTRACT Erythrocyte half-life (E, _ x,3 has been measured in 11 patients with poorly controlled blood sugar levels and compared with a normal control group to determine whether decreased red cell deformability, which occurs in diabetic patients, causes shortening of erythrocyte life or not. No difference was seen (EtT112 = 28.1 days in diabetic
INTRODUCTION
I
t has been reported that erythrocyte deformability decreases in diabetes mellitus . *-4This phenomenon can be expected to cause shortening of erythrocyte life. For this reason, erythrocyte half-life (Et-~/z) was determined in a group of diabetic patients with elevated blood sugar levels, compared with a normal control group, and the effect of poorly controlled diabetes mellitus upon erythrocyte life was investigated. MATERIAL
AND METHODS
Eleven patients with poorly controlled diabetes, determined by measuring fasting plasma glucose and I-IbA, levels (glucose > 7.8 mmol/L, HbAl > 8.6%), entered the study. Physical signs of these patients were normal. They had no history of chronic obstructive lung disease. Their lung radiographs and hemoglobin levels were normal (between 14-18 g/dL for men and 12-14 g/dL for women). They were using no drugs
Department of Internal Medicine, Hacettepe University, School of Medicine, Ankara, Turkey Reprint requests to be sent to: Dr. Sabri SayinaIp, Bahcelievler Sondurak, Eser Sitesi B-3/10 06490, Ankara, Turkey. journal of Diabetes and Its Complications 7995; 9:190-193 0 Elsevier Science Inc., 1995 655 Avenue of the Americas, New York, NY 10010
patients and 28.5 days in controls). There was also no correlation between E+1,2 and glycosylated hemoglobin (HbAI) levels. It has been concluded that poorly controlled diabetes mellitus has no effect upon erythrocyte life. (Journal of Diabete patients and Its Complications 9;3:190-193, 1995.)
except insulin or oral antidiabetics. Control group consisted of seven healthy volunteers without anemia or diabetes mellitus and matched the patient group by age (general information about patient and control groups can be seen in Table 1). Informed consent was given by all subjects. HbAl determinations were made by liquid chromatography method by using the kits produced by Sigma Diagnostics, Inc. Coefficient of variation for the assay was 0.9%. For plasma glucose determinations, A&a-B automated stat/routine analyzer was used. Hemoglobin determinations were made by model S-plus VI coulter counter produced by Coulter Electronics Inc. EtWli2 was measured by Chromium 51 Labelling.5,6 Samples (40-50 mL) of the subjects’ blood were collected in a bottle containing 10 mL acid-citrate-dextrose (ACD) solution; 75-100 clCi of high specific activity 51Cr-sodium chromate was added and incubated at room temperature for 30 min with gentle mixing; 100 mg ascorbic acid was added to the labeling vial at the end of the incubation period to reduce the unbound chromate to chromic, thereby preventing further labeling of erythrocytes by 51Cr. The whole of the blood was injected. Blood samples were obtained at 24, 36, 48 h and every day for 2 weeks. The normal elution rate was accepted to be 1.0% in both group. All sam-
SSDI
1056-8727/95/$9.50 1056-8727(94)00041-N
J Diab Comp
1995; 9:190-193
ERYTHROCYTE
TABLE 1. GENERAL INFORMATIONS ABOUT PATIENTS AND CONTROL GROUP Patients
Age (years) Mean f SD Range Sex Men Women Diabetes type NIDDM IDDM Diabetes duration (years) Mean * SD Range Hh (&-IL) Men (mean f SD) Women (mean + SD) Fasting plasma glucose (mmol/L) Mean f SD Range
Controls
53.0 f 11.7 32-70
45.7 f 11.9 31-65
3 8
4 3
LIFE
10.2 f 4.3 6-20 14.5 + 0.6 13.4 f 0.6
15.1 f 0.5 13.7 f 0.3
13.8 f 3.6 8.2-19.6
4.8 f 0.6 3.8-5.8
SD, standard deviation; IDDM, insulin-dependent diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; HB, Hemoglobin
ples were counted in a well counter and counts were plotted on semilog paper as a function of time. For statistical evaluations, Mann-Whitney U test, and Pearson product moment correlation analyses were used. RESULTS
HbAl levels were 13.9% f 2.8% in diabetic patients and 6.1% f 1.8% in controls; the difference was significant statistically (p < 0.05). Ete112was measured as 28.1 f 3.5 days in diabetic patients and 28.5 f 3.2 days in control group, there was no statistically significant difference (Table 2); and there was no correlation between I-IbAl levels and Et-r12 in diabetic patients (Y = 0.16, t = 0.49, Figure 1). One value with an erythrocyte half-life of 35 days and an HbAr level of 20% could be viewed as an outlier. But when this value was excluded, there was also no correlation between HbAl and erythrocyte half-life. DISCUSSION
Nonenzymatic glycosylation of proteins is an event that occurs in diabetics proportionally to hyperglycemia and which is claimed that it is related with chronic complications of diabetes. 7,8Hemoglobin is one of the glycosylated proteins and I-IbAl determinations are being used as an index to show long-term glycemic control.g It has been demonstrated that I-IbAl level in-
POORLY
CONTROLLED
DM
191
TABLE 2. THE COMPARISON OF PATIENT AND CONTROL GROUPS ACCORDING TO ERYTHROCYTE HALF-LIFE AND HbA, LEVELS Patients
Controls
FIbAl
13.9 f 2.8
Et-m (days)
(9.0-20.0) 28.1 f 3.5 (23.0-35.0)
6.1 f 1.8 (2.0-7.5) 28.5 f 3.2 (25.0-36.0)
HbAz,
glycosyhted
hemoglobin;
Results are expressed
7 4
AND
Et- 112, erythrocyte
P value p < 0.05
NS
half-life.
as mean f SD (range).
creases as correlated with erythrocyte age,lOJ1 and it can be used as an index of erythrocyte life in normoglycemic individuals. Accordingly, it has been seen that the levels of glycosylated hemoglobin fall in hemolytic anemias,12*13 and it is claimed that, in iron deficiency anemia, it increases in period of decreased erythrocyte production and decreases during treatment because of increasing of young erythrocyte.‘* The ability of the erythrocyte to change its shape in response to an applied force has been termed as erythrocyte deformability.*5 It is an important physiological factor that plays an essential part in the delivery of oxygen to the tissues. l6 It has been demonstrated that erythrocyte deformability decreases in diabetic patients,*-4,16 and experiments with hyperglycemic mouse erythrocytes have yielded similar resu1ts.l’ It has been claimed that two mechanisms could play a role in this event: (1) loss of elasticity due to erythrocyte membrane glycosylation and changes in lipid fraction, and (2) increasing of cytoplasmic viscosity because of glycosylation of hemoglobin.2-4 It can be expected that a decrease in erythrocyte deformability
36 34
0 0
32 . . Et112 (days)
OO
30 -28 a26 .-
0
24 a.
0
0
0
0
22 -20 J 8
I 10
12
14
16
18
20
22
HbAl(%)
FIGURE 1 The demonstration of erythrocyte half-life (E,-& values in diabetic patients according to glycosylated hemoglobin (HbAI) levels (r = 0.16, t = 0.49; no correlation was found).
192
SAYINALP
ET AL.
can cause shortening of erythrocyte life. To investigate this, we determined Et-l,2 in 11 patients with poorly controlled diabetes and compared them with the control group; we didn’t find any difference. Being expected that glycosylated hemoglobin reduces erythrocyte deformability by augmenting cytoplasmic viscosity, the relation between HbAl levels and Et-,,2 was investigated, but no correlation was found. There is only one report’* on this issue in the literature and, in some textbooks, as referenced with that study, it has been said that erythrocyte life reduces 15% in diabetic patients. In that study, made by Peterson et al., E,. II? had been measured in seven diabetic patients before and after blood sugar control. Results determined that it increased from 27 days to 31 days; a 15% increase had been seen with blood sugar control; however, this difference is not important statistically as the number of patients are few and there is not a normal control group. Thus, the results are not sufficient to lead to a precise conclusion. The design and the results of our study are somewhat different from those of Peterson et al., and they point out that erythrocyte life isn’t reduced in diabetic patients. Some hypotheses can be proposed to explain this result despite reduced erythrocyte deformability in diabetes mellitus . A first hypothesis is that, although hyperglycemia reduces erythrocyte deformability, it can make some changes that increase the resistance by affecting erythrocyte metabolism. For example, glycosylation of hemoglobin can result in an increase of oxygen affinity by reducing the binding with 2,3 diphosphoglycerate.19 In this situation, the amount of free 2,3 DPG increases, and, by the inhibition of the enzyme diphosphoglyceromutase, 3-phosphoglycerate is produced from 1,3 diphosphoglycerate directly.” This change in the direction of the chemical reaction can result in an increase of ATP formation. It can be expected that the increasing ATP level can augment erythrocyte resistance. A second hypothesis is that, although hyperglycemia reduces erythrocyte deformability, it can effect the erythrocyte degradation environment in the opposite direction. It has been suggested that the hypoglycemic environment that occurs in the spleen can play a role in erythrocyte degradation.21 The increase in blood sugar, by preventing hypoglycemia in the spleen, can prevent erythrocyte degradation. CONCLUSION In this study it has been demonstrated that erythrocyte life doesn’t change in patients with poorly controlled diabetes. Some new studies will be useful to explain erythrocyte life not changing despite reduced erythrocyte deformability in diabetes mellitus.
\ Diuh Camp 1995; 9:190-19.3
REFERENCES 1. Schmid-Schonbein H, Volger E: Red-cell aggregation and red-cell deformability in diabetes. Diabetes 25(suppl.
2):897-902, 1976. 2. McMillan
DE, Utterback NG, Puma JL: Reduced erythrocyte deformability in diabetes. Diabetes 27:895-901,
1978. 3. KiesewetterH,
JungF, Kiirber N, Wolf S, Kiehl R, Frank M, Reim M, Sitzmann FC: Microcirculation and hemorheology of children with type I diabetes. Klin Wochenschr 64:962-968, 1986.
4. Garnier
M, Attali JR, Valensi I’, Delatour-Hanss E, Gaudey F, Koutsouris D: Erythrocyte deformability in diabetes and erythrocyte membrane lipid composition. Metabolism 39:794-798, 1990.
5.
Gray SJ, Sterling K: The tagging of the red cells and plasma proteins with radioactive chromium. 1 Clin Invest 29:1604-1613, 1950.
6.
Read RC: Studies of red-cell volume and turnover radiochromium. N En@] Med 250:1021, 1954.
7. Kennedy L, Lyons TJ: Non-enzymatic Med Bull 45:174-190, 1989.
using
glycosylation.
Br
8. Kennedy L, Baynes JW: Non-enzymatic glycosylation and the chronic complications of diabetes: an overview. Diabetologia 26:93-98, 1984.
9. National committee
Diabetes Data Group: Report on glucosylated haemoglobin.
of the expert Diabetes Care
7602-606, 1984. 10.
Cordera R, Andraghetti G, Bonadonna R, Gherzi R, Marie110 M, Odetti P, Visiani G, Berri F, Adezati L: Influence of cell age and ketoaminic linkage on rapid glycosylation of hemoglobin in human red cells in vitro. Horn Metab Res 17:201-204, 1985.
11.
Elseweidy MM, Stallings M, Abraham EC: Changes in glycosylated hemoglobins with red cell aging in normal and diabetic subjects and in newborn infants of normal and diabetic mothers. 1 Lab Clin Med 102:628-636, 1983.
12.
Rigal D, Monestier M, Baboin-Joubert M, Chabauda Sassoulas D, Marseglia G, Ville D, Meyer F, Jouvenceau A: Appreciation de la duree de vie des globules rouges par le dosage de l’hemoglobine glycosylee. Presse Med
14:521-523,1985. 13.
Krauss SJ, Hahn DA, Harper D, Shell S, Baisden CR: The affinity glycated hemoglobin in a family with hereditary sypherocytosis and in other non-hemoglobinopathic hemolytic anemias. Ann Cli Lab Sci 17(5):331-
338, 1987. 14. Sluiter WJ, VanEssen Glycosylated
IH, Reistma WD, Doorenbos H: hemoglobin and iron deficiency. Lancet
531-532, 1980. 15. Sumihare N, Taniguchi erythrocte
deformability.
S, Kon H: An EPR study on Prog Biophys Molec Biol55:85-
105, 1991. 16. Mokken FC, Kedaria
M, Henny CP, Hardeman MR, Gelb AW: The clinical importance of erythrocyte deformability, a hemorrheological parameter. Ann Hemato1 64:113-z!, 1992.
17. Engstrom
KG, Grankvist K, Taljedal IB: Insulin-driven erythropoiesis may underlie impairment of erythrocyte
J Diab Camp
1995; 9:190-193
deformability in hyperinsulinaemic, hyperglycaemic oblob mice. Diubetologia 33:127-130, 1990. 18. Peterson CM, Jones KL, Koenig RJ, Melvin ET, Lehrman ML: Reversible hematologic sequelae of diabetes mellitus. Ann Intern Med 86:425-429, 1977. 19. Bunn HF, Briehl RW: The interaction of 2,3-diphospho-
ERYTHROCYTE
LIFE
AND
POORLY
CONTROLLED
DM
1%
glycerate with various human hemoglobins. J Clin lnvest 49:1088-1095, 1970. 20. Williams JW: Hematology, 4th edition. McGraw-Hill, 1990. 21. Jandle JH, Aster RI-I: Increased splenic pooling and the pathogenesis of hypersplenism. Am J Med Sci 253:383, 1967.