774
HbA,(7c) IN NEWLY DIAGNOSED INSULIN-DEPENDENT DIABETICS INITIALLY AND WEEKLY THEREAFTER
in HbAl was significantly correlated with the plasmacreatinine, although the blood-glucose did not differ among the various patient groups. Remarkably, HbAl concentrations were similar whether glucose-free (group 4; HbAl
crease
10.05±2.49%)
or
dialysate
glucose-rich
fluid
(HbAl
9.90± 1.20%) was used.
fall in
HbA,: after one week the fall (mean+S.D.7c,) was 2-5±1-2%, by two weeks it was 3-4±1-6%, and by three weeks it was 3-6±1-4%. HbAl estimated daily in cases 1 and 2 did not change after one day’s treatment, but after two days it had fallen 0.5and 1.4% and by five days 0.5and 2.0%, respectively. HbA, in three patients fell to within our range for wellcontrolled diabetics (less than z 4‘70) by two weeks.’ Rapid changes in HbA, can occur but are unlikely to be clinically significant within a week under any circumstances. Ditzel and Kjaergaards’ results also show a fall in HbA, over a period of 1-4 weeks.2 Hxmoglobin is glycosylated by a Schiff
a
base and then to a more stable Amadori rearrangement; this Schiff base may be the fraction which is rapidly dissociated in vitro as described by Svendsen et al. We conclude that changes in HbA, levels usually take a matter Ler 01 of weeks and that weeks anu mat their tneir (estimation can therefore nrovide useful clinical information. R. D. G. LESLIE D. A. PYKE Diabetic Clinic,
P. N. JOHN J. M. WHITE
King’s College Hospital, London SF5 9RS
GLYCOSYLATED HÆMOGLOBIN IN CHRONIC RENAL FAILURE
SIR,-Increased levels of the glycosylated hxmoglobin (HbAl) have been reported in patients on chronic haemodialysis. Casparie and Miedema3 wondered if this increase was the result of the high glucose content of the dialysate fluid. We have measured concentrations of HbAl and fasting bloodglucose in 45 patients with various degrees of chronic renal failure on conservative treatment (groups 1-3), in 20 patients on dialysis with glucose-free dialysate (group 4), and in 106 controls. HbAl was also measured in 6 patients on hsemodialysis with glucose (4-4 g/1) in the dialysate. HbAl was measured by ion-exchange chromatography.4 HbAl levels did not differ between patients with moderately impaired ’renal function (group i) and controls. In patients with more severe renal insufficiency (groups 2-4) the HbAl concentrations were significantly increased (table). The in1.
Leslie, R. D. G., Pyke, D. A., John, P. N., White, J. M. Lancet, 1978, ii, 958.
2. Ditzel, J., Kjaergaard, J. J. Br. med. J. 1978, i, 741. 3. Casparie, A. F., Miedema, K. Lancet, 1977, ii, 758. 4. Welch, S. G., Boucher, B. J. Diabetologia, 1978, 14,
209.
HEMOGLOBIN
Al
These data indicate that HbAl concentrations are significantly increased in patients with chronic renal failure and that this increase is not due to the dialysis procedure. In chronic renal failure a shortened life-span of the erythrocytes is well known, and low HbAl levels might be expected.Because disordered carbohydrate metabolism is well recognised in chronic renal failure, further studies should be undertaken to correlate HbAl levels to glucose-tolerance-test results in such
patients. Finally, since
we cannot yet exclude the possibility that increased HbAl levels in chronic renal failure are a consequence ’of the azotæmia, HbAlas an indicator of diabetic long-term control should be used with caution in patients with serumcreatinine levels above 2.5mg/dl.
Department of Medicine II, University of Vienna and Ludwig Boltzmann Institute for Clinical Endocrinology and Nuclear Medicine A-1090 Vienna, Austria
G. SCHERNTHANER K. H. STUMMVOLL M. M. MÜLLER
ALBUMIN EXCRETION IN OPERATING SURGEONS AND IN HYPERTENSION
SIR The cardiovascular response to stress is a topic of interest, especially in the context of hypertension. Prompted by a report from Foster et al.1 that surgeons doing
current
intra-abdominal operations consistently had high heart-rates (mean 121 beats/min, mean peak value 137 beats/min) we have been exploring vascular permeability in stress by measuring urinary albumin excretion in surgical colleagues. Six surgeons collected timed urine samples before, during, and after five major intra-abdominal operations and one vaginal hysterectomy. Fig. 1 shows that urinary albumin excretion increased from 5.8+3.3 µg/min (S.D.) before surgery to 15.2±11.2 ug/min during the operation (2 p=0.011 after logarithmic transformation). The more experienced the surgeon the less was the change in albumin excretion (2p=0.003). No changes were seen when the surgeons worked in the outpatient clinic. No significant increase in urinary &bgr;2 microglobulin excretion was seen, indicating undisturbed tubular protein reabsorption. Thus the increase in albumin excretion in stress seems to be of glomerular origin, due to increased glomerular permeability. The ability to inhibit such increases in vascular permeability during stress would be of great interest, especially for the treatment of hypertension. Increased vascular permeability may play a role in the development of hypertensive vascular 5. Bunn, H. F., Haney, D. N., Kamm, S., Gabbay, K. H., Gallop, P. M. J. clin. Invest. 1976, 57, 1652. 6 DeFronzo, R. A., Andres, R., Edgar, P., Walker, W. G. Medicine, 1973, 52, 469. 1. Foster, G. E., Evans, D. F., Hardcastle, J. D. Lancet, 1978, i, 1323.
VALUES IN PATIENTS IN CHRONIC RENAL FAILURE
Cr=plasma-creatinine (mg/dl). *Mean HbAl values higher than control mean for group 2 (two-tailed P
HbA,(7c) IN NEWLY DIAGNOSED INSULIN-DEPENDENT DIABETICS INITIALLY AND WEEKLY THEREAFTER
in HbAl was significantly correlated with the plasmacreatinine, although the blood-glucose did not differ among the various patient groups. Remarkably, HbAl concentrations were similar whether glucose-free (group 4; HbAl
crease
10.05±2.49%)
or
dialysate
glucose-rich
fluid
(HbAl
9.90± 1.20%) was used.
fall in
HbA,: after one week the fall (mean+S.D.7c,) was 2-5±1-2%, by two weeks it was 3-4±1-6%, and by three weeks it was 3-6±1-4%. HbAl estimated daily in cases 1 and 2 did not change after one day’s treatment, but after two days it had fallen 0.5and 1.4% and by five days 0.5and 2.0%, respectively. HbA, in three patients fell to within our range for wellcontrolled diabetics (less than z 4‘70) by two weeks.’ Rapid changes in HbA, can occur but are unlikely to be clinically significant within a week under any circumstances. Ditzel and Kjaergaards’ results also show a fall in HbA, over a period of 1-4 weeks.2 Hxmoglobin is glycosylated by a Schiff
a
base and then to a more stable Amadori rearrangement; this Schiff base may be the fraction which is rapidly dissociated in vitro as described by Svendsen et al. We conclude that changes in HbA, levels usually take a matter Ler 01 of weeks and that weeks anu mat their tneir (estimation can therefore nrovide useful clinical information. R. D. G. LESLIE D. A. PYKE Diabetic Clinic,
P. N. JOHN J. M. WHITE
King’s College Hospital, London SF5 9RS
GLYCOSYLATED HÆMOGLOBIN IN CHRONIC RENAL FAILURE
SIR,-Increased levels of the glycosylated hxmoglobin (HbAl) have been reported in patients on chronic haemodialysis. Casparie and Miedema3 wondered if this increase was the result of the high glucose content of the dialysate fluid. We have measured concentrations of HbAl and fasting bloodglucose in 45 patients with various degrees of chronic renal failure on conservative treatment (groups 1-3), in 20 patients on dialysis with glucose-free dialysate (group 4), and in 106 controls. HbAl was also measured in 6 patients on hsemodialysis with glucose (4-4 g/1) in the dialysate. HbAl was measured by ion-exchange chromatography.4 HbAl levels did not differ between patients with moderately impaired ’renal function (group i) and controls. In patients with more severe renal insufficiency (groups 2-4) the HbAl concentrations were significantly increased (table). The in1.
Leslie, R. D. G., Pyke, D. A., John, P. N., White, J. M. Lancet, 1978, ii, 958.
2. Ditzel, J., Kjaergaard, J. J. Br. med. J. 1978, i, 741. 3. Casparie, A. F., Miedema, K. Lancet, 1977, ii, 758. 4. Welch, S. G., Boucher, B. J. Diabetologia, 1978, 14,
209.
HEMOGLOBIN
Al
These data indicate that HbAl concentrations are significantly increased in patients with chronic renal failure and that this increase is not due to the dialysis procedure. In chronic renal failure a shortened life-span of the erythrocytes is well known, and low HbAl levels might be expected.Because disordered carbohydrate metabolism is well recognised in chronic renal failure, further studies should be undertaken to correlate HbAl levels to glucose-tolerance-test results in such
patients. Finally, since
we cannot yet exclude the possibility that increased HbAl levels in chronic renal failure are a consequence ’of the azotæmia, HbAlas an indicator of diabetic long-term control should be used with caution in patients with serumcreatinine levels above 2.5mg/dl.
Department of Medicine II, University of Vienna and Ludwig Boltzmann Institute for Clinical Endocrinology and Nuclear Medicine A-1090 Vienna, Austria
G. SCHERNTHANER K. H. STUMMVOLL M. M. MÜLLER
ALBUMIN EXCRETION IN OPERATING SURGEONS AND IN HYPERTENSION
SIR The cardiovascular response to stress is a topic of interest, especially in the context of hypertension. Prompted by a report from Foster et al.1 that surgeons doing
current
intra-abdominal operations consistently had high heart-rates (mean 121 beats/min, mean peak value 137 beats/min) we have been exploring vascular permeability in stress by measuring urinary albumin excretion in surgical colleagues. Six surgeons collected timed urine samples before, during, and after five major intra-abdominal operations and one vaginal hysterectomy. Fig. 1 shows that urinary albumin excretion increased from 5.8+3.3 µg/min (S.D.) before surgery to 15.2±11.2 ug/min during the operation (2 p=0.011 after logarithmic transformation). The more experienced the surgeon the less was the change in albumin excretion (2p=0.003). No changes were seen when the surgeons worked in the outpatient clinic. No significant increase in urinary &bgr;2 microglobulin excretion was seen, indicating undisturbed tubular protein reabsorption. Thus the increase in albumin excretion in stress seems to be of glomerular origin, due to increased glomerular permeability. The ability to inhibit such increases in vascular permeability during stress would be of great interest, especially for the treatment of hypertension. Increased vascular permeability may play a role in the development of hypertensive vascular 5. Bunn, H. F., Haney, D. N., Kamm, S., Gabbay, K. H., Gallop, P. M. J. clin. Invest. 1976, 57, 1652. 6 DeFronzo, R. A., Andres, R., Edgar, P., Walker, W. G. Medicine, 1973, 52, 469. 1. Foster, G. E., Evans, D. F., Hardcastle, J. D. Lancet, 1978, i, 1323.
VALUES IN PATIENTS IN CHRONIC RENAL FAILURE
Cr=plasma-creatinine (mg/dl). *Mean HbAl values higher than control mean for group 2 (two-tailed P
