Prostacyclin and Thromboxane in Non-Insulin Dependent Diabetes: The Chlorpropamide Alcohol Flush Reaction Revisited

1984 ◽  
Vol 67 (6) ◽  
pp. 633-638 ◽  
Author(s):  
Colin Johnston ◽  
Frank Carey ◽  
Robert A. Forder ◽  
Duncan Haworth
Keyword(s):  
Plasma Levels ◽  
Thromboxane B2 ◽  
Insulin Dependent Diabetes ◽  
Diabetic Patients ◽  
Peripheral Vascular ◽  
Basal Plasma ◽  
Insulin Dependent ◽  
Alcohol Flushing ◽  
Insulin Dependent Diabetic ◽  
Venous Plasma

1. Levels of immunoreactive 6-oxo-prostaglandin F1α (6-oxo-PGF1α) and thromboxane B2 (TXB2) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF1α did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB2 were 125 ± 14 and 128 ± 8 pg/ml for volunteers and NIDDS respectively. 2. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF1α levels. Measurement of the combined plasma levels of 6-oxo-PGF1α, 13,14-dihydro-6-oxo-PGF1α, 13,14-dihydro-6,15-dioxo-PGF1α and 6-oxo-PGE1 indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF1α levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites. 3. Measurement of 6-oxo-PGF1α and TXB2 in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon. 4. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF1α and TXB2 in CPAF and other pathophysiological conditions in man.

Effect of Posture and Acute Glycaemic Control on the Excretion of Retinol-Binding Protein in Normoalbuminuric Insulin-Dependent Diabetic Patients

1993 ◽  
Vol 84 (4) ◽  
pp. 461-467 ◽  
Author(s):  
Carlo Catalano ◽  
Peter H. Winocour ◽  
Susan Gillespie ◽  
Ian Gibb ◽  
K. George M. M. Alberti
Keyword(s):  
Blood Glucose Concentration ◽  
Excretion Rate ◽  
Binding Protein ◽  
Insulin Dependent Diabetes ◽  
Retinol Binding Protein ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Protein Excretion ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

1. It has been suggested that tubular damage may precede gomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01). 5. The study demonstrates that retinol-binding protein excretion is increased in insulin-dependent diabetes in the absence of microalbuminuria and that this increase in retinol-binding protein excretion is particularly pronounced after acute euglycaemia. Acute tubular dysfunction related to acute changes in glucose control appears to be the most likely explanation, but established tubular damage could also be implicated. Postural variation in retinol-binding protein excretion was not detected.

Effects of somatostatin on the behaviour of thromboxane B2 and β-thromboglobulin in type I diabetes

1985 ◽  
Vol 109 (1) ◽  
pp. 104-107 ◽  
Author(s):  
G. Gragnoli ◽  
A. M. Signorini ◽  
I. Tanganelli
Keyword(s):  
Platelet Function ◽  
Type I Diabetes ◽  
Thromboxane B2 ◽  
Diabetic Patients ◽  
Base Line ◽  
Type I ◽  
Control Subjects ◽  
Pharmacological Studies ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

Abstract. Pharmacological studies have shown that the addition of somatostatin to insulin promotes a more rapid recovery from diabetic ketoacidosis. However, contradictory results have been reported concerning the action of somatostatin on platelet function, frequently deranged in diabetes. Therefore the plasma levels of thromboxane B2, a stable metabolite of proaggregatory thromboxane A2 and of β-thromboglobulin, a marker of platelet activation, were studied in 9 control subjects and in 13 insulin-dependent diabetic patients before and during somatostatin injection, administered as an initial 250 μg iv bolus followed by infusion of 300 μg over 3 h. In both groups, after somatostatin infusion thromboxane B2 and β-thromboglobulin levels showed, respectively, a progressive fall and an increase up to the second hour. Over the next hour thromboxane B2 increased and μ-thromboglobulin decreased but their levels did not return to basal values. During this experiment β-thromboglobulin plasma values in diabetic patients did not differ from those of control subjects. In contrast, thromboxane B2, decreased in relation to pharmacological treatment, maintained elevated levels. Our data, however, demonstrate that the dose of somatostatin used, produced in the diabetic patients a normal fall of thromboxane B2 in terms of percentage of base-line values, but increases of β-thromboglobulin lower than in control subjects. It is suggested that platelet function should be evaluated when somatostatin is used in the treatment of poorly controlled type I diabetes.

scholarly journals Plasma 6-keto-PGF1?, thromboxane B2 and PGE2 in Type 1 (insulin-dependent) diabetic patients during exercise

Diabetologia ◽  
1987 ◽  
Vol 30 (7) ◽  
pp. 460-463 ◽  
Author(s):  
T. Mourits-Andersen ◽  
I. W. Jensen ◽  
P. N�hr Jensen ◽  
J. Ditzel ◽  
J. Dyerberg
Keyword(s):  
Thromboxane B2 ◽  
Diabetic Patients ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

Glyoxalase System in Clinical Diabetes Mellitus and Correlation with Diabetic Complications

1994 ◽  
Vol 87 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Antony C. McLellan ◽  
Paul J. Thornalley ◽  
Jonathan Benn ◽  
Peter H. Sonksen
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Haemoglobin A1c ◽  
Glyoxalase System ◽  
Control Subjects ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P < 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P < 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean ± SD (n) pmol/106 erythrocytes], combined diabetic patients, 3.37 ± 0.85 (24), control subjects 4.76 ± 1.95 (8) P < 0.05; D-lactate [mean ± SD or median, range (n) nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P < 0.001, non-insulin-dependent patients, 20.0 ± 8.9, 2.6-48.4 (105), P < 0.001, control subjects 9.7 ± 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P>0.05). 3. The activities of glyoxalase enzymes in erythrocytes were increased: glyoxalase I activity [mean ± SD (n) m-units/106 erythrocytes] was increased in diabetic patients, relative to normal control subjects: insulin-dependent patients, 4.35 ± 1.54 (41), P < 0.001; non-insulin-dependent patients, 4.61 ± 1.79 (101), P < 0.001; control subjects, 3.21 ± 1.81 (21); glyoxalase II activity [mean ± SD (n) m-units/106 erythrocytes] was increased in the non-insulin-dependent diabetic patient group, relative to normal control subjects [non-insulin-dependent diabetic patients, 2.10 ± 0.46 (102); subject controls, 1.83 ± 0.27 (21); P < 0.05]. 4. In insulin-dependent diabetic patients, the concentration of methylglyoxal correlated positively with the duration of diabetes, and the concentration of D-lactate correlated positively with haemoglobin A1c and negatively with the reduced glutathione concentration. D-Lactate concentration correlated positively with blood glucose concentration in patients with non-insulin-dependent diabetes mellitus. 5. There was a positive logistic correlation of duration of disease with retinopathy, nephropathy, neuropathy, or any combination thereof. Retinopathy also gave a positive logistic correlation with haemoglobin A1c concentrations and a negative logistic correlation with D-lactate concentration. 6. When paired for duration of diabetes, patients with retinopathy, neuropathy or nephropathy, or any combination thereof, had significantly higher age, level of haemoglobin A1c and glyoxalase I activity than patients with uncomplicated diabetes (P < 0.05). 7. We conclude that the glyoxalase system is modified in erythrocytes in both insulin-dependent and non-insulin-dependent diabetic patients and that this modification is related to the development of diabetic complications.

Increased plasma levels of apolipoprotein A-IV in insulin-dependent diabetic patients

1994 ◽  
Vol 109 (1-2) ◽  
pp. 247-248
Author(s):  
S. Visvikis ◽  
M. Zaiou ◽  
O. Ziegler ◽  
R. Gueguen ◽  
P. Drouin ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Diabetic Patients ◽  
Apolipoprotein A ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients

Diabetes ◽  
1985 ◽  
Vol 34 (11) ◽  
pp. 1127-1133 ◽  
Author(s):  
R. K. Mayfield ◽  
P. V. Halushka ◽  
H. J. Wohltmann ◽  
M. Lopes-Virella ◽  
J. K. Chambers ◽  
...  
Keyword(s):  
Platelet Function ◽  
Insulin Infusion ◽  
Diabetic Patients ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Continuous Insulin Infusion
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