DTT7
CASE REPORT
Pre- and Postoperative Glucose Levels for Eliciting Hypoglycaemic Responses in a Patient with Insulinoma H. Vea", R. Jorde", C. Sagerb, S. Vaalere, J.Sundsfjordc, A. Revhaugd Departments of Vnternal Medicine, "Pharmacology, 'Clinical Chemistry and dSurgery, University Hospital of Trorns0, and 'Hormone Laboratory, Aker University Hospital, Oslo, Norway
Counterregulatory hormones and hypoglycaemic symptoms were studied during a gradual decline in plasma glucose in a 66-year-old man before and 9 weeks after removal of an insulin-producing tumour. Before surgery the adrenaline started to respond first at plasma glucose 2.8 mmol I-'. He reported no autonomic symptoms although plasma glucose fell to 2.3 mmol I-' with a corresponding adrenaline rise to 4.64 nmol I-'. After surgery adrenaline responded at a plasma glucose of 3.7 mmol I-' and he started to sweat and tremble at a plasma glucose of 3.1 mmol I-' (corresponding adrenaline 2.63 nmol I-'). The lack of autonomic symptoms preoperatively may indicate adrenaline insensitivity, possibly as a result of repeated hypoglycaemia. KEY WORDS
Counterregulation Hypoglycaemia Autonomic symptoms Adrenergic responses lnsulinoma
Introduction In a study on young Type 1 diabetic patients Amiel et a/.' found that a significantly lower blood glucose level was needed to elicit a hypoglycaemic response after a period of 2-6 months with intensified insulin therapy. Thus, the blood glucose fall needed for activation of counterregulatory hormones and hypoglycaemic symptoms seems to depend on the prevalent blood glucose level. If so, one would expect patients with insulinoma to respond first at very low glucose values, and this was indeed described by Davis and Shamoon.* We have studied, and now report, a male patient with insulinorna before and 9 weeks after successful removal of the tumour.
insulin only dropped from 210 to 147 pmol I-l. He was transferred to the University of Tromsp, where a CT-scan revealed contrast enhancement in the uncinate region of the pancreas. A calcium-infusion test was performed during which blood glucose decreased from 3.5 to 2.9 rnmol I-' with a corresponding increase in serum insulin from 144 to 1015 pmol I-l, also indicating an i n ~ u l i n o m a .No ~ further endocrine or other abnormality was found. At surgery a single tumour (diameter 1.2 cm) was found in the uncinate process. The tumour was enucleated and histological examination confirmed the diagnosis of insulinoma. Postoperatively, the fasting blood glucose values were normal, he had no glycosuria and no symptoms of diabetes.
Procedures
Patient and Methods Case A 66-year-old man, who had previously undergone a Billroth II operation in 1964 for peptic ulceration, was well until September 1991 when he experienced a severe episode of confusion and erratic behaviour, requiring admission to the local hospital. The clinical examination was normal, but on the second day after admission, a random blood glucose of 2.3 mmol 1 - l was recorded. The patient was subsequently submitted to a prolonged fast, and after 22 h the blood glucose had dropped to 1.7 mmol I-l. During the same fasting period serum Correspondence to: Dr H. Vea, Department of Medicine, University Hospital of Tromso, N-9038 Tromso, Norway.
950
The patient was studied in the metabolic research laboratory before and 9 weeks after resection of the insulinoma. A cannula was inserted into a left antecubital vein for constant infusions of rapid acting insulin (1.5 mU kg-' min-') and 24 % glucose. A second cannula for blood sampling was inserted into a dorsal hand vein on the right arm. This arm was placed in a heated box (63 "C) to arterialize the venous blood and the line was kept patent with 0.9 % NaCI. After a resting and stabilizing period of approximately 30 min the plasma glucose was allowed to fall gradually during 180 min (0.17 mmol IF1 every 10 min). Plasma glucose was measured every 10 min and the desired glucose level achieved by adjusting the glucose infusion rate accordingly. Blood samples were drawn and a symptom questionnaire filled out every 10 min.
0742-3071 /92/100950-04$07.00
0 1992 by John Wiley & Sons,
Ltd.
DIABETIC MEDICINE, 1992; 9: 950-953
nm
CASE REPORT
If serious clinical symptoms of hypoglycaemia occurred before plasma glucose had fallen to 2.0 mmol I-', our protocol was to stop the insulin infusion and normalize the blood glucose by intravenous glucose. Written informed consent was obtained from the patient before participation. The protocol was approved by the regional ethical committee.
;
5.0
h
45
d
v Q,
.5
;
4.0 35 30
2.5
2.0
4
Measurements Plasma glucose was measured bedside using a Beckman glucose analyser (Beckman, Fullerton, CA, USA). Plasma adrenaline, plasma noradrenaline, and serum pancreatic polypeptide (PP) were measured as previously d e ~ c r i b e d . ~Determination ,~ of serum cortisol was based on enhanced luminescence (Amerlite diagnostics Ltd, Amersham, England).
Symptoms
;
15 10
a 4
O 5
00
Plasma glucose ( m m o l 1-') Figure 2. Adrenaline repsonses (nrnol I-') to gradual hypoglycaernia before (-0)and 9 weeks after (-0) removal of the insulinorna
The patient scored four neuroglycopenic (dizziness, blurred vision, faintness, difficulty in concentration) and four autonomic (trembling, sweating, palpitations, feeling nervous) symptoms on a line from 0 (no symptoms) to maximal 10 cm. The symptoms were added together to give a neuroglycopenic score and an autonomic score.
Statistical Methods The plasma glucose levels where hypoglycaemic responses first occur are given as the mean between the plasma glucose level where responses were more than 2 SD above base level, followed by an unequivocal, sustained increase, and the preceding plasma glucose.
Results Plasma glucose was lowered gradually on both days (Figure 1). The hormonal responses occurred at a lower plasma glucose level before than after surgery (adrenaline 2.8 vs 3.7 mmol I-', cortisol 3.0 vs 3.7 mmol I-', PP
2.3 vs 3.1 mmol I-'( Figures 2, 3, 4). Since the plasma glucose was lower throughout the study preoperatively, the hormone levels are plotted against the corresponding glucose levels instead of time in the figures. Preoperatively noradrenaline increased significantly at a plasma glucose of 2.3 mmol I-' whereas no increase was seen after the surgery (Figure 5). The patient reported no autonomic symptoms before surgery and only fatigue as a neuroglycopenic symptom when the study was stopped at a blood glucose level of 2.3 mmol I-' (Table 1). After surgery both autonomic symptoms (sweating and trembling) and neuroglycopenia (fatigue) were reported at plasma glucose 3.1 mmol I-' (Table 2). The other hypoglycaemic symptoms asked for were not noted by the patient.
n 3
I
* H
600 -
500
~
A\ $.
4
I
55 r 50
45
~
4 0
-
35
-
30 -
2.5 -
15 I
I
0
30
60
90
1211
150
180
Plasma glucose ( m m o l 1-')
Time (min) Figure 1. Arterialized venous plasma glucose (rnrnol I-') during the insulin-induced hypoglycaemia before (0-0and ) 9 weeks after (0-0) removal of the insulinorna
Figure 3. Cortisol responses (nmol I-') to gradual hypoglycaemia before (A-A) and 9 weeks after (A-A) removal of the insulinorna
GLUCOSE LEVELS FOR HYPOCLYCAEMIC RESPONSES IN A PATIENT WITH INSULINOMA
951
CASE REPORT Table 2. Postoperative symptom score, from 1 (symptom absent) to 10 (symptom severe) Plasma glucose mmol I-' 4.6 4.3 30
Dizziness Blurred vision Faintness Difficult to concentrate Trembling Sweating Palpitations Feeling nervous
A
zo: 10
e$-
d
4 L
'1.0
'
45
'
'
40
I
35
2.0
2 5
3 0
P l a s m a g l u c o s e ( m m o l I-') Figure 5. Noradrenaline responses (nmol I-') to gradual hypoglycaemia before (0-0) and 9 weeks after (0-0) removal of the insulinoma
Table 1. Preoperativesymptom score, from 1 (symptom absent) to 10 (symptom severe) Plasma glucose mmol I-' 4.6 4.2 Dizziness Blurred vision Faintness Difficult to concentrate Trembling Sweating Palpitations Feeling nervous
952
1 1 1 1 1 1 1 1
1 1 2 1 2 2 1 1
1 1 2 1 2 4 1 1
1 1 2 1 2 7 1 1
1 1 2 1 2 9 1 1
Discussion
7 1
5 5
1 1 1 1 1 1 1 1
2.0
Figure 4. Pancreatic polypeptide responses (pmol 1-l) to gradual hypoglycaemia before (A-A) and 9 weeks after (A-A) removal of the insulinoma
'I
1 1 1 1 1 1 1 1
3.2 3.1 3.0 3.1 3.0
_J
Plasma g l u c o s e ( m m o l 1-')
0 4 / ' '
1 1 1 1 1 1 1 1
(1
1 1 1 1 1 1 1 1
)I
2.5 2.3 2.3 2.3 2.3 1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 5 1 1 1 1 1
In the present study we have confirmed the previous observation in patients with insulinoma2,6 of a lower blood glucose level needed to elicit hypoglycaemic responses with a return towards normal after removal of the tumour. Consistent with the presenting symptoms of neuroglycopaenia causing the hospitalization, no autonomic symptoms were scored during the preoperative study, in spite of substantial elevations of adrenaline and noradrenaline. This was in sharp contrast to the situation after surgery, when adrenergic symptoms were elicited at a much lower adrenaline level. Possibly, the lack of sympathetic symptoms preoperatively may be ascribed to a lack of adrenaline sensitivity. The high adrenaline levels due to hypoglycaemia may promote a desensitization by uncoupling and/or internalization of the P-receptors, resulting in lower CAMP levels and thereby reduce the adrenaline sensitivity. However, to confirm this hypothesis, one would have to perform adrenaline infusion tests, either in patients with insulinoma, or more available, in patients on intensified insuIi n therapy. An alternative explanation would be that the patient was too neuroglycopaenic to note the autonomic symptoms. However, the difference in symptom pattern preand postoperatively was remarkable clinically and not just recorded in the questionnaire. The degree of hyperinsulinaemia has been reported to affect the symptoms and hormonal responses to hypoglycaemia.' Unfortunately, the insuIin levels were not measured in our study, so we cannot rule out that endogenous insulin production preoperatively augmented the circulating insulin levels and thereby had some effect on the hypoglycaemic responses. In conclusion, in our patient with insulinoma, we have found the endocrine and symptom responses to start at plasma glucose some 0.8 mmol I-' higher after removal of the tumour. The lack of autonomic symptoms preoperatively was possibly caused by adrenergic insensitivity as a result of repeated hypoglycaemia. H. VEA €T AL.
Dm
CASE REPORT
Acknowledgements The present study was financially supported by The Norwegian Research Council for Science and the Humanities, Nordisk Insulinfond, the Norwegian Diabetes Association, and the Norwegian Council on Cardiovascular Research. We wish to thank T. Arnesen, R. Jaeger, K. Mindeberg and T. Arild for their skilful technical assistance.
3.
4.
5.
References 1. Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes 1988; 37: 901-907. 2. Davis MR, Shamoon H. Deficient counterregulatory
6.
7.
GLUCOSE LEVELS FOR HYPOGLYCAEMIC RESPONSES IN A PATIENT W I T H INSULINOMA
hormone responses during hypoglyemia in a patient with insulinoma. ) Clin Endocrinol Metab 1991; 72: 788-792. Brunt LM, Veldhuis JD, Dilley WG, Farndon JR, Santen RJ, Leight GS, et a/. Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with @-cell neoplasms of the pancreas. 1 Clin Endocrinol Metab 1986; 62: 210-216. Sager G, Trovik T, Slprrdal L, Jzger R, Prytz PS, Brox J, et a/. Catecholamine binding and concentrations in acute phase plasma after surgery. Scan ) Clin Lab lnvest 1988; 48: 419-424. Jorde R, Burhol PG. Effect of jejunoileal bypass operation and Billroth II resection on postprandial plasma pancreatic polypeptide release. Scand j Castroenterol 1982; 17: 613-61 7. Maran A, Taylor J, Macdonald IA, Amiel SA. Evidence for reversibility of defective counterregulation in a patient with insulinoma. Diabetic Med 1992; 9: 765-768. Kerr D, Reza M, Smith N, Leatherdale BA. Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM. Diabetes 1991; 40: 1057-1062.
953
CASE REPORT
Pre- and Postoperative Glucose Levels for Eliciting Hypoglycaemic Responses in a Patient with Insulinoma H. Vea", R. Jorde", C. Sagerb, S. Vaalere, J.Sundsfjordc, A. Revhaugd Departments of Vnternal Medicine, "Pharmacology, 'Clinical Chemistry and dSurgery, University Hospital of Trorns0, and 'Hormone Laboratory, Aker University Hospital, Oslo, Norway
Counterregulatory hormones and hypoglycaemic symptoms were studied during a gradual decline in plasma glucose in a 66-year-old man before and 9 weeks after removal of an insulin-producing tumour. Before surgery the adrenaline started to respond first at plasma glucose 2.8 mmol I-'. He reported no autonomic symptoms although plasma glucose fell to 2.3 mmol I-' with a corresponding adrenaline rise to 4.64 nmol I-'. After surgery adrenaline responded at a plasma glucose of 3.7 mmol I-' and he started to sweat and tremble at a plasma glucose of 3.1 mmol I-' (corresponding adrenaline 2.63 nmol I-'). The lack of autonomic symptoms preoperatively may indicate adrenaline insensitivity, possibly as a result of repeated hypoglycaemia. KEY WORDS
Counterregulation Hypoglycaemia Autonomic symptoms Adrenergic responses lnsulinoma
Introduction In a study on young Type 1 diabetic patients Amiel et a/.' found that a significantly lower blood glucose level was needed to elicit a hypoglycaemic response after a period of 2-6 months with intensified insulin therapy. Thus, the blood glucose fall needed for activation of counterregulatory hormones and hypoglycaemic symptoms seems to depend on the prevalent blood glucose level. If so, one would expect patients with insulinoma to respond first at very low glucose values, and this was indeed described by Davis and Shamoon.* We have studied, and now report, a male patient with insulinorna before and 9 weeks after successful removal of the tumour.
insulin only dropped from 210 to 147 pmol I-l. He was transferred to the University of Tromsp, where a CT-scan revealed contrast enhancement in the uncinate region of the pancreas. A calcium-infusion test was performed during which blood glucose decreased from 3.5 to 2.9 rnmol I-' with a corresponding increase in serum insulin from 144 to 1015 pmol I-l, also indicating an i n ~ u l i n o m a .No ~ further endocrine or other abnormality was found. At surgery a single tumour (diameter 1.2 cm) was found in the uncinate process. The tumour was enucleated and histological examination confirmed the diagnosis of insulinoma. Postoperatively, the fasting blood glucose values were normal, he had no glycosuria and no symptoms of diabetes.
Procedures
Patient and Methods Case A 66-year-old man, who had previously undergone a Billroth II operation in 1964 for peptic ulceration, was well until September 1991 when he experienced a severe episode of confusion and erratic behaviour, requiring admission to the local hospital. The clinical examination was normal, but on the second day after admission, a random blood glucose of 2.3 mmol 1 - l was recorded. The patient was subsequently submitted to a prolonged fast, and after 22 h the blood glucose had dropped to 1.7 mmol I-l. During the same fasting period serum Correspondence to: Dr H. Vea, Department of Medicine, University Hospital of Tromso, N-9038 Tromso, Norway.
950
The patient was studied in the metabolic research laboratory before and 9 weeks after resection of the insulinoma. A cannula was inserted into a left antecubital vein for constant infusions of rapid acting insulin (1.5 mU kg-' min-') and 24 % glucose. A second cannula for blood sampling was inserted into a dorsal hand vein on the right arm. This arm was placed in a heated box (63 "C) to arterialize the venous blood and the line was kept patent with 0.9 % NaCI. After a resting and stabilizing period of approximately 30 min the plasma glucose was allowed to fall gradually during 180 min (0.17 mmol IF1 every 10 min). Plasma glucose was measured every 10 min and the desired glucose level achieved by adjusting the glucose infusion rate accordingly. Blood samples were drawn and a symptom questionnaire filled out every 10 min.
0742-3071 /92/100950-04$07.00
0 1992 by John Wiley & Sons,
Ltd.
DIABETIC MEDICINE, 1992; 9: 950-953
nm
CASE REPORT
If serious clinical symptoms of hypoglycaemia occurred before plasma glucose had fallen to 2.0 mmol I-', our protocol was to stop the insulin infusion and normalize the blood glucose by intravenous glucose. Written informed consent was obtained from the patient before participation. The protocol was approved by the regional ethical committee.
;
5.0
h
45
d
v Q,
.5
;
4.0 35 30
2.5
2.0
4
Measurements Plasma glucose was measured bedside using a Beckman glucose analyser (Beckman, Fullerton, CA, USA). Plasma adrenaline, plasma noradrenaline, and serum pancreatic polypeptide (PP) were measured as previously d e ~ c r i b e d . ~Determination ,~ of serum cortisol was based on enhanced luminescence (Amerlite diagnostics Ltd, Amersham, England).
Symptoms
;
15 10
a 4
O 5
00
Plasma glucose ( m m o l 1-') Figure 2. Adrenaline repsonses (nrnol I-') to gradual hypoglycaernia before (-0)and 9 weeks after (-0) removal of the insulinorna
The patient scored four neuroglycopenic (dizziness, blurred vision, faintness, difficulty in concentration) and four autonomic (trembling, sweating, palpitations, feeling nervous) symptoms on a line from 0 (no symptoms) to maximal 10 cm. The symptoms were added together to give a neuroglycopenic score and an autonomic score.
Statistical Methods The plasma glucose levels where hypoglycaemic responses first occur are given as the mean between the plasma glucose level where responses were more than 2 SD above base level, followed by an unequivocal, sustained increase, and the preceding plasma glucose.
Results Plasma glucose was lowered gradually on both days (Figure 1). The hormonal responses occurred at a lower plasma glucose level before than after surgery (adrenaline 2.8 vs 3.7 mmol I-', cortisol 3.0 vs 3.7 mmol I-', PP
2.3 vs 3.1 mmol I-'( Figures 2, 3, 4). Since the plasma glucose was lower throughout the study preoperatively, the hormone levels are plotted against the corresponding glucose levels instead of time in the figures. Preoperatively noradrenaline increased significantly at a plasma glucose of 2.3 mmol I-' whereas no increase was seen after the surgery (Figure 5). The patient reported no autonomic symptoms before surgery and only fatigue as a neuroglycopenic symptom when the study was stopped at a blood glucose level of 2.3 mmol I-' (Table 1). After surgery both autonomic symptoms (sweating and trembling) and neuroglycopenia (fatigue) were reported at plasma glucose 3.1 mmol I-' (Table 2). The other hypoglycaemic symptoms asked for were not noted by the patient.
n 3
I
* H
600 -
500
~
A\ $.
4
I
55 r 50
45
~
4 0
-
35
-
30 -
2.5 -
15 I
I
0
30
60
90
1211
150
180
Plasma glucose ( m m o l 1-')
Time (min) Figure 1. Arterialized venous plasma glucose (rnrnol I-') during the insulin-induced hypoglycaemia before (0-0and ) 9 weeks after (0-0) removal of the insulinorna
Figure 3. Cortisol responses (nmol I-') to gradual hypoglycaemia before (A-A) and 9 weeks after (A-A) removal of the insulinorna
GLUCOSE LEVELS FOR HYPOCLYCAEMIC RESPONSES IN A PATIENT WITH INSULINOMA
951
CASE REPORT Table 2. Postoperative symptom score, from 1 (symptom absent) to 10 (symptom severe) Plasma glucose mmol I-' 4.6 4.3 30
Dizziness Blurred vision Faintness Difficult to concentrate Trembling Sweating Palpitations Feeling nervous
A
zo: 10
e$-
d
4 L
'1.0
'
45
'
'
40
I
35
2.0
2 5
3 0
P l a s m a g l u c o s e ( m m o l I-') Figure 5. Noradrenaline responses (nmol I-') to gradual hypoglycaemia before (0-0) and 9 weeks after (0-0) removal of the insulinoma
Table 1. Preoperativesymptom score, from 1 (symptom absent) to 10 (symptom severe) Plasma glucose mmol I-' 4.6 4.2 Dizziness Blurred vision Faintness Difficult to concentrate Trembling Sweating Palpitations Feeling nervous
952
1 1 1 1 1 1 1 1
1 1 2 1 2 2 1 1
1 1 2 1 2 4 1 1
1 1 2 1 2 7 1 1
1 1 2 1 2 9 1 1
Discussion
7 1
5 5
1 1 1 1 1 1 1 1
2.0
Figure 4. Pancreatic polypeptide responses (pmol 1-l) to gradual hypoglycaemia before (A-A) and 9 weeks after (A-A) removal of the insulinoma
'I
1 1 1 1 1 1 1 1
3.2 3.1 3.0 3.1 3.0
_J
Plasma g l u c o s e ( m m o l 1-')
0 4 / ' '
1 1 1 1 1 1 1 1
(1
1 1 1 1 1 1 1 1
)I
2.5 2.3 2.3 2.3 2.3 1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 1 1 1 1 1 1
1 1 5 1 1 1 1 1
In the present study we have confirmed the previous observation in patients with insulinoma2,6 of a lower blood glucose level needed to elicit hypoglycaemic responses with a return towards normal after removal of the tumour. Consistent with the presenting symptoms of neuroglycopaenia causing the hospitalization, no autonomic symptoms were scored during the preoperative study, in spite of substantial elevations of adrenaline and noradrenaline. This was in sharp contrast to the situation after surgery, when adrenergic symptoms were elicited at a much lower adrenaline level. Possibly, the lack of sympathetic symptoms preoperatively may be ascribed to a lack of adrenaline sensitivity. The high adrenaline levels due to hypoglycaemia may promote a desensitization by uncoupling and/or internalization of the P-receptors, resulting in lower CAMP levels and thereby reduce the adrenaline sensitivity. However, to confirm this hypothesis, one would have to perform adrenaline infusion tests, either in patients with insulinoma, or more available, in patients on intensified insuIi n therapy. An alternative explanation would be that the patient was too neuroglycopaenic to note the autonomic symptoms. However, the difference in symptom pattern preand postoperatively was remarkable clinically and not just recorded in the questionnaire. The degree of hyperinsulinaemia has been reported to affect the symptoms and hormonal responses to hypoglycaemia.' Unfortunately, the insuIin levels were not measured in our study, so we cannot rule out that endogenous insulin production preoperatively augmented the circulating insulin levels and thereby had some effect on the hypoglycaemic responses. In conclusion, in our patient with insulinoma, we have found the endocrine and symptom responses to start at plasma glucose some 0.8 mmol I-' higher after removal of the tumour. The lack of autonomic symptoms preoperatively was possibly caused by adrenergic insensitivity as a result of repeated hypoglycaemia. H. VEA €T AL.
Dm
CASE REPORT
Acknowledgements The present study was financially supported by The Norwegian Research Council for Science and the Humanities, Nordisk Insulinfond, the Norwegian Diabetes Association, and the Norwegian Council on Cardiovascular Research. We wish to thank T. Arnesen, R. Jaeger, K. Mindeberg and T. Arild for their skilful technical assistance.
3.
4.
5.
References 1. Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes 1988; 37: 901-907. 2. Davis MR, Shamoon H. Deficient counterregulatory
6.
7.
GLUCOSE LEVELS FOR HYPOGLYCAEMIC RESPONSES IN A PATIENT W I T H INSULINOMA
hormone responses during hypoglyemia in a patient with insulinoma. ) Clin Endocrinol Metab 1991; 72: 788-792. Brunt LM, Veldhuis JD, Dilley WG, Farndon JR, Santen RJ, Leight GS, et a/. Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with @-cell neoplasms of the pancreas. 1 Clin Endocrinol Metab 1986; 62: 210-216. Sager G, Trovik T, Slprrdal L, Jzger R, Prytz PS, Brox J, et a/. Catecholamine binding and concentrations in acute phase plasma after surgery. Scan ) Clin Lab lnvest 1988; 48: 419-424. Jorde R, Burhol PG. Effect of jejunoileal bypass operation and Billroth II resection on postprandial plasma pancreatic polypeptide release. Scand j Castroenterol 1982; 17: 613-61 7. Maran A, Taylor J, Macdonald IA, Amiel SA. Evidence for reversibility of defective counterregulation in a patient with insulinoma. Diabetic Med 1992; 9: 765-768. Kerr D, Reza M, Smith N, Leatherdale BA. Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM. Diabetes 1991; 40: 1057-1062.
953
