[Assuring care of diabetics in the Czech Republic. Recommendations of the Czech Diabetes Society].
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Czech Republic↗
Biomedical subjects
J Skrha
Publications and source records attributed to J Skrha.
Clinical research of glucose metabolism.
Glucose metabolism in diabetes and in hypoglycemic states has been studied at IIIrd Medical Department for more than 30 years. The research is now concentrated on the evaluation of insulin action on receptor and postreceptor levels and in biochemical changes accompanying early stages of diabetic microangiopathy. The changes of insulin action has been examined by using the clamp techniques also in patients with organic hyperinsulinism. We study molecular changes of insulin action and pathogenesis of vascular complications.
Diabetes Mellitus↗
[Neuroendocrine carcinoma of the pancreas with the hyperinsulinism syndrome].
In a 26-year-old woman with symptoms of hyperinsulinism explorative laparotomy revealed a pancreatic tumour metastatizing into the liver. Intensive cytostatic therapy led to a temporary inhibition of hyperinsulinism, however, in the course of two years massive infiltration of the retroperitoneum, left adrenal, gastric wall, liver, mesentery and abdominal lymph nodes by a tumour occurred. On necroptic examination the tumour had characteristics of a neuroendocrine carcinoma with carcinoid features. Part of the tumour cells were argyrophil; reliable evidence of insulin production, which during the terminal stage of the disease played again a major part in the clinical picture, was made possible only by the use of a very sensitive Czech made antibody against C peptide.
Adult↗
[Relation between hypertriacylglycerolemia and the action of insulin in type 2 diabetes mellitus].
BACKGROUND: Insulin resistance and hypertriacylglycerolaemia are part of the X syndrome and are supposed to be interrelated. The objective of the present trial was to evaluate the impact of hypolipidaemic treatment on the action of insulin evaluated by means of a so-called hyperinsulimaemic clamp and by examination of insulin receptors. METHODS AND RESULTS: To eight type 2 diabetics with mild hypertriacylglycerolaemia for three months ethophylline clofibrate (Duolip) was administered and for three months phenofibrate (Lipanthyl). Before and during treatment parameters of diabetes compensation were examined (blood sugar level, fructosamine and glycolysate haemoglobin), insulin sensitivity, using an isoglycaemic hyperinsulinaemic clamp and insulin receptors on red blood cells. Lipanthyl caused a more marked drop of triacylglycerol (by 46%) than Duolip forte (by 20%). Hypolipidaemic treatment did not affect diabetes compensation. As compared with healthy subjects, in diabetics before treatment a reduced insulin sensitivity was found, evaluated either by the index of insulin sensitivity (24.0 +/- 0.8, as compared with 35.5 +/- 4.9 mumol/kg/min per mU/l x 100, p < 0.05) or metabolic glucose clearance (3.7 +/- 0.9, as compared with 6.3 +/- 1.0 ml/kg/min, p < 0.01) and a slightly reduced insulin bond with receptors (p < 0.05). Duolip treatment led to a drop of insulin sensitivity and concurrent rise of affinity of insulin receptors (p < 0.01), while Lipanthyl was not manifested by marked changes. The authors did not find a significant correlation between the drop of triacylglycerol levels and insulin sensitivity in different types of treatment, which obviously is due to the small number of examinations. CONCLUSIONS: Therapy with ethophylline clofibrate of fenofibrate was not manifested in type 2 diabetics by a changes in the compensation of the disease. Hypertriacylglycerolaemia exists as an independent factor which is rather the consequence than cause of insulin resistance.
Adult↗
[The effect of Proglicem in patients with an organic hyperinsulinism syndrome].
BACKGROUND: Organic hyperinsulinism is treated as a rule conservatively with diazoxide (Proglicem) which has a hyperglycaemic effect. In some patients, however, treatment fails and severe hypoglycaemia persists. The objective of the present investigation was to find simple criteria for evaluation of the aptness (effectiveness) of this treatment. METHODS AND RESULTS: In 11 patients with a confirmed insulinoma Proglicem was administered for five days (3 mg/kg body weight) and serum insulin and the blood sugar level as well as their ratio (IRI:G) were followed-up. In eight patients the IRI/G coefficient declined from 10.5 +/- 7.7 to 5.8 +/- 2.9 (p < 0.001); only in three patients the coefficient increased from 4.6 +/- 2.9 to 14.9 +/- 12.3 (p < 0.001). Coefficient "k" from the modified Bergman model for the intravenous glucose tolerance test had identical results; there was statistically significant agreement between the two examinations. CONCLUSIONS: To assess the effectiveness of diazoxide treatment (Proglicem) on hypoglycaemia in nesidiomas it is sufficient to evaluate the IRI/G coefficient (on fasting) before and during diazoxide treatment (Proglicem, Schering Corp.).
Adult↗
Early changes of serum N-acetyl-beta-glucosaminidase, tissue plasminogen activator and erythrocyte superoxide dismutase in relation to retinopathy in type 1 diabetes mellitus.
Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.
Acetylglucosaminidase↗
Insulin action in patients with insulinoma influenced by pharmacological and surgical therapy.
Organic hyperinsulinism due to insulinoma is accompanied by changes of insulin action on receptor and postreceptor levels. The influence of conservative and surgical treatment on insulin sensitivity was examined by euglycaemic hyperinsulinaemic clamps in ten patients with insulinoma. The "responders" (n = 5) and "non-responders" (n = 5) to diazoxide treatment were distinguished by using fasting plasma glucose and insulin concentrations. The index of insulin sensitivity was significantly decreased in pretreated "responders" as compared to healthy persons (19 +/- 3 vs 39 +/- 6 and 20 +/- 3 vs 37 +/- 5 mumol.kg-1.min-1 per mU.l-1 x 100, p < 0.01) and it was improved during diazoxide administration (27 +/- 4 vs 19 +/- 3 and 35 +/- 12 vs 20 +/- 3 mumol.kg-1.min-1 per mU.l-1 x 100, p < 0.05). Significantly decreased insulin sensitivity in pretreated "non-responders" (25 +/- 5 vs 39 +/- 6 and 28 +/- 6 vs 37 +/- 5 mumol.kg-1.min-1 per mU.l-1 x 100, p < 0.05) was not improved by diazoxide administration. Metabolic clearance rate of glucose was significantly higher in "non-responders" as compared to "responders" and healthy persons (12.7 +/- 3.4 vs 7.9 +/- 2.7 and 7.4 +/- 2.4 ml.min-1.kg-1, p < 0.05) already in pretreated state. An inverse relationship was found between metabolic clearance rate of glucose and of insulin (r = 0.72, p < 0.001). Plasma glucose, insulin concentration, index of insulin sensitivity, and metabolic clearance rate of glucose and of insulin were normalized after surgical removal of an insulinoma in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Glycosaminoglycans in urine of type 1 diabetic patients.
Diabetic nephropathy is accompanied by changes of glomerular and tubular functions manifesting already in the early stages by an increase of glycosaminoglycans excretion into urine. We evaluated urinary glycosaminoglycan excretion in 38 Type 1 diabetic patients with no markers of developed nephropathy. Glycosaminoglycan excretion related to creatinine concentration was significantly higher in diabetic patients with or without retinopathy than in healthy persons (3.9, 1.2-12.7 or 3.7, 0.9-15.9 vs 2.0, 0.8-5.1 micrograms/mumol creatinine, p < 0.01). A positive correlation between glycosaminoglycan excretion and albuminuria was observed in all diabetic patients (r = 0.60, p < 0.01). Urinary glycosaminoglycan excretion did not correlate with serum fructosamine concentration.
Adult↗
[Albuminuria and N-acetyl-beta-glucosaminidase activity in a prospective study of type I diabetics].
The authors investigated a group of 47 type I diabetics in a prospective study extending over 8 years. Every year they evaluated the albuminuria and the N-acetyl-beta-glucosaminidase (NAG) activity in serum and urine and the results were compared with the state of compensation of diabetes and with the clinical finding on the ocular fundus. During the eight-year period newly manifested microalbuminuria developed in 8 of 32 patients (25%) who at the onset had a normal finding. In patients with newly manifested microalbuminuria the authors found a significant rise of the fructosamine serum concentration (p < 0.05) and at the same time a rise of serum NAG activity (p < 0.05). A positive correlation was proved between the serum NAG activity and glycated haemoglobin (r = 0.67, p < 0.01). In 13 patients (28%) in the course of the eight-year period the finding on the ocular fundus deteriorated. In these patients the NAG serum activity was elevated already at the onset of the investigation, while albuminuria rose in the course of the mentioned period. Dynamic changes of the NAG serum activity along with albuminuria can serve as bio-chemical markers of developing microangiopathy the manifestation of which is hastened by deteriorated compensation of diabetes.
Acetylglucosaminidase↗
[Evaluation of the status of diabetes mellitus during a 2-year period using traditional methods and determination of glycosylated hemoglobin A1c and fructosamine in the blood].
In the course of two years the authors checked 23 diabetic patients (13 type 2, 10 type 1), using the traditional approach, by assessment of haemoglobin A1c and serum fructosamine. The patients were classified according to compensation into four and three groups resp. Assessment of haemoglobin A1c evaluated the patients, in the same group as the traditional evaluation in 57.7% into the best compensated group and in 62.5% into the worst compensated group. In fructosamine agreement with traditional evaluation in the best compensated group was in 84.2% and in the worst compensated group in 50.0%. In 40.2% the evaluation was in agreement for all three methods of evaluation, differences between evaluation according to haemoglobin A1c and serum fructosamine were recorded in 51.5%. Assessment of haemoglobin A1c and serum fructosamine improves information on the state of diabetes, concurrent estimation of both is, however, often associated with difficulties as regards interpretation. These problems are discussed in the presented paper.
Diabetes Mellitus↗
[Diabetic angiopathies 1990].
In the submitted review the author summarizes recent knowledge on the biochemistry and pathophysiology of diabetic micro- and macroangiopathy. Hyperglycaemia and hyperinsulinaemia are the main cause of a complicated complex of changes which take place at different levels of the organism. Their consequence is an irreversible affection of the vascular wall with a subsequent effect on the organism as a whole.
Diabetic Angiopathies↗
A six-year follow-up of the relationship between N-acetyl-beta-glucosaminidase and albuminuria in relation to retinopathy.
Fifty patients with Type 1 diabetes mellitus were observed over 6 years. Serum and urinary N-acetyl-beta-glucosaminidase (NAG) activity, and albuminuria were measured in groups of patients subdivided according to ophthalmological findings. Significantly higher mean serum NAG activity was found at the beginning of the study in patients who later developed diabetic retinopathy in comparison with those who did not (geometric mean (2SD range) 19.7 (12.4-31.2) vs 14.4 (9.5-22.7) U l-1, p less than 0.01). Urinary NAG activity was significantly higher in all groups of diabetic patients than in healthy control subjects (p less than 0.05). A significant increase in albumin:creatinine ratio during the study was found in patients with newly developed diabetic retinopathy compared with patients who did not (at 6 years 1.33 (0.40-4.43) vs 0.75 (0.24-2.31) g mol-1, p less than 0.01). No differences in either biochemical variable were found between hypertensive and normotensive diabetic patients at the end of the study. The results suggest that both serum NAG activity and albuminuria may serve as early functional indicators of diabetic retinopathy.
Acetylglucosaminidase↗
N-acetyl-beta-glucosaminidase and albuminuria in acromegaly.
Significantly increased albuminuria and N-acetyl-beta-glucosaminidase activity in serum and urine have been observed in acromegalic patients in comparison with healthy persons (P less than 0.001). No relationship between these biochemical variables and serum growth hormone or insulin concentration was found in our group of patients. Significant correlation was determined between urinary NAG activity and albuminuria of acromegalic patients (r = 0.84).
Acetylglucosaminidase↗
[The development of theories on the mechanisms of insulin action].
In 1924 Laufberger formulated his block theory on the action of insulin. Its basic thesis that insulin prevents the new formation of glucose and its supply into the blood stream is still valid, although knowledge on the multiple action of insulin expanded substantially. The theory put forward in 1955 by Levine and Goldstein which ascribed all insulin actions to the influence on the cellular membrane permeability for glucose, could, however, not explain all data associated with insulin, the knowledge of which was expanded steadily. At present the mechanism of insulin action is explained most comprehensively by the concept based on the bond of insulin to its membrane receptor which by activation of tyrosine kinase it contains induces either cascade phosphorylation of intracellular protein kinases or (and) leads to the release of the "second messenger" from the cell membrane, i.e. of glycosyl-phosphatidyl inositol. In both instances activation of the glucose and amino acids transmitter from the medium into the cells results, as well as activation of enzymes catalyzing in the cell various degrees of carbohydrate, fat and protein metabolism.
Czechoslovakia↗
[Fructosamine--a dynamic indicator of compensation in diabetes].
The serum fructosamine concentration was evaluated in 22 diabetics on admission to hospital and after intensified treatment with an insulin pump which was indicated on account of decompensation of diabetes. The drop of the mean glucose concentration in blood after 12 days of treatment correlated with the statistically significant drop of the serum fructose concentration (r = 0.69, p less than 0.001). Between the glucose and fructosamine serum concentration no relationship was observed, as long as the mean glucose concentration was calculated for a period shorter than the previous seven days. A highly significant correlation was observed between the rate of fructosamine decline and the mean blood sugar level (r = 0.94, p less than 0.001). From the dynamic changes ensues that when the mean blood sugar level declined by 1 mmol/l, the fructosamine level declined on average by 0.13 mmol/l. The results suggest a more rapid turnover of glycosylated proteins, as compared with data in the literature pertaining to non-glycosylated proteins.
Adult↗
[Analysis of dynamic changes in glycosylated blood proteins using a computer model].
UNLABELLED: The authors elaborated a computer model of albumin glycosylation based on the irreversible glycosylation reaction with first order kinetics. The dynamics of changes of glycosylated albumin in relation to the glycaemic profile was confirmed with an older model of haemoglobin glycosylation. By means of regression analysis parameters of the model in three groups of patients were calculated. CONCLUSION: 1. Stratification of the red cell pool is the reason why there is a smaller clinical difference between glycosylated protein and haemoglobin than corresponds to their half-times. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated ones. 3. Higher levels of glycosylated proteins sometimes do not correspond to model calculations are probably due to other factors.
Computer Simulation↗
Plasma free N-terminal fibronectin 30-kDa domain as a marker of endothelial dysfunction in type 1 diabetes mellitus.
The plasma free N-terminal fibronectin 30-kDa domain was measured in 44 type 1 diabetic patients and in 20 healthy subjects. A significantly raised mean concentration of a free N-terminal fibronectin 30-kDa domain was found in plasma of diabetic patients with proliferative retinopathy as compared with healthy persons (P less than 0.001). A positive correlation was observed between free N-terminal fibronectin 30-kDa domain and von Willebrand factor in plasma of all examined subjects (r = 0.62, P less than 0.01). A similar correlation was present between 30-kDa domain and albuminuria (r = 0.56, P less than 0.01). However, no relationship was found between fibronectin 30-kDa domain and control of diabetes as assessed by fructosamine concentration. The free N-terminal fibronectin 30-kDa domain may be used as a marker of actual endothelial cell dysfunction in diabetes.
Adult↗