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.

Plasma Endothelin Levels and Vascular Effects of Intravenous l-Arginine Infusion in Subjects with Uncomplicated Insulin-Dependent Diabetes Mellitus

1994 ◽  
Vol 87 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Ronald A. Smulders ◽  
Coen D. A. Stehouwer ◽  
Cornelis G. Olthof ◽  
Gerard J. Van Kamp ◽  
Tom Teerlink ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Fluid ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Vascular Effects ◽  
Arginine Infusion ◽  
Control Subjects ◽  
Insulin Dependent

1. Uncomplicated insulin-dependent diabetes mellitus is associated with generalized vasodilatation. This vasodilatation is believed to contribute to the development of microvascular complications. The endothelium plays an important role in the regulation of vascular tone. 2. To investigate the role of endothelial mediators, we measured plasma endothelin levels and studied the vascular effects of intravenous l-arginine (the precursor of NO) in 10 male type 1 diabetic patients and 10 non-diabetic subjects. 3. The baseline plasma endothelin level was significantly lower in the diabetic patients [mean 1.7 (SD 0.5) versus 2.1 (0.4) pmol/l; P < 0.05] than in the control subjects. 4. During l-arginine infusion, plasma cyclic GMP (the second messenger for NO) increased in the control subjects [from 5.1 (2.9) to 6.9 (2.9) nmol/l; P < 0.05 versus saline] and in the diabetic patients [from 4.6 (1.8) to 5.7 (2.2) nmol/l; P = 0.09]. l-Citrulline (a by-product of NO synthesis from l-arginine) increased in both groups. The responses to l-arginine were not significantly different between the control subjects and the diabetic patients. The plasma atrial natriuretic peptide level did not change in either group during infusion of l-arginine or of an equal volume of isotonic saline. 5. Blood pressure decreased slightly during l-arginine administration in both groups. In control subjects, the extracellular fluid volume in the lower leg increased during l-arginine infusion as compared with saline; in the diabetic patients both l-arginine and saline increased the extracellular fluid volume. 6. In conclusion, the vascular effects of l-arginine are similar in men with uncomplicated insulin-dependent diabetes mellitus and in control subjects. Whether these effects are due to an increase in NO synthesis remains unclear. The increase in extracellular fluid volume during saline infusion in diabetic patients suggests an increase in microvascular permeability in

Hepatic drug metabolism is increased in poorly controlled insulin-dependent diabetes mellitus

1990 ◽  
Vol 123 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Steven Goldstein ◽  
Anna Simpson ◽  
Paul Saenger
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Control ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Hepatic Drug Metabolism ◽  
Hepatic Drug ◽  
Insulin Dependent ◽  
Cytochrome P 450

Abstract. In addition to increased glycosylation of hemoglobin, abnormalities of other heme proteins such as cytochrome P-450 might also occur in patients with insulin-dependent diabetes mellitus. Antipyrine is a useful marker drug for cytochrome P-450 dependent hepatic drug metabolism. Antipyrine kinetics and urinary excretion of antipyrine metabolites were measured in 14 patients with insulin-dependent diabetes mellitus in poor metabolic control. Improvement in diabetic control in 9 patients, as measured by more normal HbA1 values, led to normalization of plasma antipyrine half-time (t½) and metabolism: the mean antipyrine t½ slowed from 4.7±0.2 (sem) initially to 7.8±0.3 h in these 9 patients and was thus nearly identical to that of normal subjects 8.6±1.0. Antipyrine plasma clearance improved in the 9 diabetic patients whose diabetic control improved. The apparent volume of distribution was normal on both occasions in the diabetic patients. These findings provide a new argument for tight metabolic control in patients with insulin-dependent diabetes mellitus.

scholarly journals FTIR Spectroscopic Investigation of Mineral Structure of Streptozotocin Induced Diabetic Rat Femur and Tibia

2003 ◽  
Vol 17 (2-3) ◽  
pp. 627-633 ◽  
Author(s):  
Handan Boyar ◽  
Belma Turan ◽  
Feride Severcan
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Rat ◽  
Carbonate Content ◽  
Diabetic Patients ◽  
Type I ◽  
Mineral Density ◽  
Insulin Dependent

Diabetes mellitus (DM) can be accepted as a heterogenous multi organ disorder that can affect various systems of the human body. Disorders include retinopathy, neuropathy, cardiomyopathy, musculoskeletal abnormalities such as diminished bone formation and bone healing retardation. Low bone mineral density is often mentioned as a complication for patients with insulin dependent diabetes mellitus (type I DM). Streptozotocin (STZ) induced diabetic rats are good models for investigation of the complications of insulin dependent diabetes. In the present study, the effects of STZ induced diabetes on the mineral environment of rat bones namely femur and tibia were studied by Fourier transform infrared (FTIR) spectroscopic technique. The results revealed that mineral crystal sizes increased and carbonate content decreased for diabetic femur and tibia. These changes can be due to the formation of osteoporosis which is widely seen in diabetic patients.

Attempted Suicide by Insulin Overdose in Insulin-Dependent Diabetic Adolescents

PEDIATRICS ◽  
1988 ◽  
Vol 81 (4) ◽  
pp. 526-528
Author(s):  
Yifrah Kaminer ◽  
Douglas R. Robbins
Keyword(s):  
Diabetes Mellitus ◽  
Adolescent Girls ◽  
Attempted Suicide ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Insulin Overdose

Two cases of attempted suicide by insulin overdose in adolescent girls with insulin-dependent diabetes mellitus were observed. It is possible that suicidal insulin overdose in adolescents is more common than reports suggest and that it may often be unrecognized.

Impaired Endothelium-Dependent and Independent Dilatation of Forearm Resistance Arteries in Men with Diet-Treated Non-Insulin-Dependent Diabetes: Role of Dyslipidaemia

1996 ◽  
Vol 91 (5) ◽  
pp. 567-573 ◽  
Author(s):  
G. F. Watts ◽  
S. F. O'brien ◽  
W. Silvester ◽  
J. A. Millar
Keyword(s):  
Sodium Nitroprusside ◽  
Density Lipoprotein ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Resistance Arteries ◽  
Control Subjects ◽  
Vasodilatory Response ◽  
Insulin Dependent

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 μg/min) and sodium nitroprusside (3 and 10 μg/min), respectively, into the brachial artery. NG-monomethyl-l-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-l-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.

Islet cell transplantation for insulin-dependent diabetes mellitus: perspectives from the present and prospects for the future

2000 ◽  
Vol 2 (6) ◽  
pp. 1-28 ◽  
Author(s):  
Derek W.R. Gray ◽  
Nicolas Titus ◽  
Lionel Badet
Keyword(s):  
Diabetes Mellitus ◽  
Immune Modulation ◽  
Insulin Dependent Diabetes Mellitus ◽  
Human Islet ◽  
Insulin Dependent Diabetes ◽  
Current Status ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Islet Cell Transplantation ◽  
Insulin Dependent

The long-term complications of insulin-dependent diabetes mellitus have become a major health care problem, and it is now clear that they arise from inadequate homeostatic control of blood glucose by injected replacement insulin. Transplantation of pancreatic islets is arguably the most logical approach to restoring metabolic homeostasis in people with diabetes. This review looks at the current status of human islet transplantation and the problems that remain. These include: (1) the limited supply of human islet tissue available for transplantation; (2) the adverse effects of current immunosuppressive protocols on diabetic patients; (3) the problems of primary nonfunction of the transplanted islets; (4) the rejection of islets; and (5) the recurrence of autoimmune diabetic disease. Some of the approaches that might solve these problems are then examined: (1) immune modulation to reduce or prevent immune attack by the recipient's immune system; (2) immunoisolation to prevent recognition of the islet graft; (3) induction of tolerance; (4) xenotransplantation using islets derived from animals; and (5) gene therapy.

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