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Biomedical subjects

T Koschinsky

Publications and source records attributed to T Koschinsky.

At least 19 recordsLinked to original sources
PubMed1991

Diabetes and arterial disease.

Macroangiopathy (or atherosclerosis) is a common and chronic complication in diabetic patients. Unlike other diabetic complications, atherosclerosis is not unique to diabetes, confounding analysis of its relationship with the diabetic condition. Evidence of an independent role for diabetes in the development of atherosclerosis remains equivocal. The main determinant of macrovascular disease may be an interaction between diabetes and the aging process. Similarly the question of a relationship between macrovascular disease and good metabolic control remains unanswered. Macroangiopathy in diabetic populations seems to be related to similar predictors and pathological mechanisms operating in the general population. However, after analysis of these common risk factors for macroangiopathy, a diabetes-specific risk remains. Low-density lipoprotein metabolism is markedly disturbed in poorly controlled diabetic patients. This is manifest as a concert of actions which increase formation of foam cells and fatty streaks. The next step in the atherosclerotic process, the formation of fibrous plaques, may be associated with the platelet hyperactivity seen in diabetes. This may promote overshooting of repair mechanisms at the vessel wall. Release of a specific diabetic serum growth factor from the platelets may be responsible for the later stages of fibrous plaque development and the increased atherosclerotic risk in diabetes.

Adult↗
PubMed1991

Oral antidiabetic combination therapy with sulphonylureas and metformin.

In a multicentre trial in general practice, a total of 1823 type 2 diabetics, not adequately controlled by diet and maximal sulphonylurea therapy, were treated with additional metformin 850--2 550 mg/d for 12 weeks. The average postprandial blood sugar decreased from 15.48 mmol/l to 10.43 mmol/l, HbA1 fell from 11.0% to 9.1%. Serum triglycerides decreased from an initial level of 2.87 mmol/l to 2.41 mmol/l an mean total cholesterol from 6.76 mmol/l to 6.16 mmol/l. In addition, body weight and blood pressure declined steadily. All the described changes were statistically significant. The metformin-sulphonylurea combination therapy was generally well tolerated. Gastrointestinal side effects occurred in about 7% of patients, but mainly in the first week of treatment, generally disappearing spontaneous as therapy was continued. Side effects led to a discontinuation of the treatment in 4.2% of patients.

Administration, Oral↗
PubMed1988

New approach to technical and clinical evaluation of devices for self-monitoring of blood glucose.

Despite the wide distribution of devices for self-monitoring of blood glucose (SMBG), there is no internationally accepted agreement on a standardized procedure for their evaluation. This is due to incomplete or even inappropriate technical evaluation and to inadequate evaluation criteria for their clinical acceptability. To provide adequate information on the performance of these devices over the whole clinically relevant range for SMBG (30-350 mg/dl), a standardized test procedure has been established for technical (accuracy, precision, and total deviation) and clinical (acceptance analysis) evaluation. To demonstrate the potency of this new approach, the following SMBG devices and test strips were evaluated: Chemstrip bG batch (n = 10), Glucostix batch (n = 2), Accu-Check II (n = 5), Diascan (n = 5), Diascan strip batch (n = 4), Glucocheck SC (n = 4), and Glucometer II (n = 4). The devices and test strips were examined by trained technicians, and in addition, 1 Chemstrip bG batch and 2 Accu-Check II meters were examined by 10 and 5 trained diabetic patients, respectively. Even the best-performing device did not achieve the American Diabetes Association's goal that SMBG measurements should be within 15% of the reference value. Instead, the maximal total deviation within the clinically relevant blood glucose range reached values that equalled deviations from the reference value between 16 and 108%. Three of 36 devices were classified as good, 29 as acceptable, and 4 as unacceptable for clinical use. In conclusion, this new approach to the technical and clinical evaluation of devices for SMBG is easy to perform and provides more realistic and comparable information for clinical use and approval than commonly used methods.

Blood Glucose Self-Monitoring↗
PubMed1987

[Clinical testing of a new blood glucose measuring system. A cooperative study at 8 centers].

The glucometer II system is a small measurement device with built-in batch-specific pressbutton calibration. The corresponding test strip "Glucostix" uses a two-color system. The blood glucose test strip can be evaluated both visually and by instrument. The precision determined in series was between 2.0% and 6.7% using control sera. The day-to-day precision was between 1.5% and 7.9%. Comparison of the methods on the basis of 781 and 109 capillary blood samples respectively revealed a good agreement between the hexokinase method or the glucose oxidase method (Beckman analyser) and the glucometer II values. The precision of measurement by the system was comparable in the two test strip batches employed. Visual reading of the test strips revealed a good agreement with the laboratory method in the hypoglycemic and normoglycemic range; at higher concentrations of blood glucose, a trend to underestimation of the measurement values was shown. The easy handling and small size of the instrument facilitates measurement of blood glucose by the patient under everyday conditions.

Blood Glucose↗
PubMed1987

Increased growth stimulation of human vascular cells by serum from patients with primary hyper-LDL-cholesterolemia.

Premature atherosclerosis in hypercholesterolemic patients may be due, in part, to increased growth of vascular cells. Therefore, the growth stimulating effect of serum and serum fractions from patients with primary hyper-LDL-cholesterolemia (LDL-cholesterol: 7.5 +/- 1.7 mmol/l) and from healthy subjects on human arterial smooth muscle cells and fibroblasts has been investigated over 5-7 days in culture. Human hypercholesterolemic sera increased the growth of both cell types up to a mean of 133% compared with normal sera (100%) (P less than 0.001). Removal of the dialyzable serum fraction (m.w. less than 3,500 daltons) reduced the growth effect of the hypercholesterolemic sera by 32% (P less than 0.001) and of the normal sera by 11% (P less than 0.01). Readdition of the hypercholesterolemic serum dialysate to its dialyzed serum restored completely the original growth effect. There was no significant difference in growth stimulation between the dialyzed hypercholesterolemic and normal sera excluding a major additional growth effect by LDL-cholesterol. The low molecular weight growth factor(s) of hypercholesterolemic serum (m.w. less than 3,500 daltons) showed a linear dependence of growth stimulation over a 20-fold concentration range. Increased amounts of this factor(s) might easily penetrate the arterial wall, thus contributing to atherogenesis.

Adult↗
PubMed1987

Vascular growth factors and the development of macrovascular disease in diabetes mellitus.

The pathogenesis of macrovascular disease in diabetes mellitus is still incompletely understood. Within the various pathomechanisms abnormal growth of vascular cells is well established as an intrinsic part of the angiopathic process. In this regard, there are different groups of vascular growth factors that are of potential relevance for the development of macrovascular disease in diabetes : hormones, locally released growth factors of platelet and of arterial wall cell origin. The following hormones whose blood levels could increase under various conditions in diabetes have to be considered : growth hormone, insulin-like growth factor I and II and insulin. Human platelets contain at least eight growth peptides or proteins that all stimulate in vitro growth of arterial wall cells : platelet-derived-, epidermal-, fibroblast-, diabetic serum-, endothelial- and transforming growth factor, vascular endothelial cell proliferation factor and platelet-derived endothelial cell mitogen. In serum and plasma from type II diabetics only the diabetic serum growth factor has been shown to be increased. Platelets from type I and II diabetic patients contain increased growth stimulating activity. This increased growth activity returned to normal levels in both types of diabetes after strict metabolic control. Arterial endothelial and smooth muscle cells, fibroblasts and monocyte/macrophages of different species release at least in culture a variety of growth factors that could participate in an autocrine or paracrine manner in the growth regulation of the arterial wall. Diabetes may affect the release of these factors, but direct evidence to which degree this would contribute to the development of macrovascular disease is lacking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Sera from type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells.

Diabetic angiopathy may be due, in part, to increased growth in vascular cells. We have investigated serum growth factors in Type 2 (non-insulin-dependent) diabetic and healthy subjects and their effect on cultured human arterial smooth muscle cells and fibroblasts. Removal of the dialyzable serum fraction (mol. wt. less than 12,000) reduced the growth effect of the diabetic sera by 37% (2p less than 0.005) and of the non-diabetic sera by only 8% (2p less than 0.01). In contrast, there was no difference in growth stimulation between the dialyzed diabetic or non-diabetic sera. Complete recovery of the dialyzable serum growth fraction was also obtained at a mol. wt. below 3,500. Ten times the concentration of the low molecular weight growth factor (mol. wt. less than 3,500) from diabetic sera stimulated growth of fibroblasts or arterial smooth muscle cells by a mean of 243% or 174% and from non-diabetic sera by a mean of 146% or 137%, respectively (2p less than 0.01). The growth stimulating potency of this serum fraction (mol. wt. less than 3,500) contained in 10% diabetic sera, was two to ten times higher than that of human growth hormone or insulin, added in amounts equivalent to 10% or physiological serum concentrations. This diabetic serum growth factor was further characterized by: (1) linear dependence of growth stimulation over a concentration range of twenty times and by (2) reduction of the growth stimulating activity to control levels by pretreatment: (a) at 95 degrees C for 30 min, or (b) with two different proteases: Serva pronase E (Streptomyceus griseus) or Calbiochem protease (Subtilisin calsberg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Vascular growth factors and the development of macrovascular disease in diabetes mellitus.

There are two different classes of humoral growth factors for arterial smooth muscle and endothelial cells that age of potential relevance for the development of macrovascular disease inn diabetes mellitus: hormones (growth hormone, insulin like growth factor I and II, insulin) and locally released growth factors of platelet origin. The following hormones have to be considered: Increased growth hormone plasma levels might contribute to macrovascular disease, but its actual relevance remains to be determined. Insulin like growth factor I and II are present in vivo and stimulate growth of vascular cells in vitro but their relevance for macrovascular disease in diabetes is unproven. To insulin, see Dr. Stout's paper. Human platelets contain at least six growth peptides or proteins that all stimulate in vitro growth of arterial wall cells: platelet derived growth factor, epidermal growth factor, platelet derived endothelial cell mitogen, endothelial growth factor, diabetic serum growth factor (DSGF), transforming growth factor-beta. As their plasma concentrations have not been shown to be increased in diabetes increased local availability at sites of stimulated platelet aggregation has been postulated. Therefore, their relevance for macrovascular disease i diabetics is based mainly on circumstantial evidence. The concentration of DSGF of platelet origin depends on the metabolic control: it increases in vivo in poorly controlled diabetics and is normalized after 2-3 weeks of good metabolic control in the same diabetic patient. The growth potency of DSGF from poorly controlled diabetics is greater than that of physiological amounts of insulin or growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1984

[Reflolux--a new test system for the self control of blood glucose for diabetics].

Correctness and accuracy of Reflolux, a new microprocessor-controlled minireflectometer for measuring blood-glucose concentrations, were tested in ten instruments. There was good agreement between the Reflolux values and those obtained in the laboratory with the hexokinase method, over the entire range of 40-350 mg/dl with a relatively small margin of error. Thus the Reflolux provides even in the hypoglycaemic range values accurate enough for everyday use by a diabetic. An important advantage of this test system lies in the use of Haemo-Glukotest 20-800 test strips which, in conjunction with the Reflolux, provide a visual color comparison for blood-glucose levels in the range of 20-800 mg/dl.

Blood Glucose↗
PubMed1984

[Improved metabolic state in insulin-tested diabetes. Self-testing of blood or urine glucose on 2 days per week].

Randomized serial tests of their metabolic state over four weeks, without self-testing and during daily urinary glucose-profile testing (4 tests) with the Diabur-Test or blood-glucose levels with the Haemo-Gluco-test 20-800 (5 tests daily) on two days weekly were undertaken on 27 unselected insulin-treated outpatient diabetes. HbA1, blood glucose, serum cholesterol, triglycerides and VLDL, LDL and HDL cholesterol were the target values. The following metabolic values were significantly reduced (P less than 0.05) during blood-glucose self-testing, compared with the results during the non-testing phase: HbA1 on average by 11%, blood-glucose (starving) by 20%, serum cholesterol by 9%, serum triglycerides by 13%. Self-testing of urinary glucose (compared with the test-free phase) brought little improvement in the metabolic state. The results of self-testing were the more impressive the worse the metabolic state during the phase without self-testing. Except for VLDL and HDL cholesterol, changes in HbA1 correlated well during all phases with changes in the other metabolic values (P less than 0.05).

Adolescent↗
PubMed1984

[New instrument for blood glucose determination. Results of a clinical trial of the Reflocheck].

Reflocheck, a new microprocessor-regulated apparatus determining blood sugar levels was tested in six laboratories. In the range of 20-450 mg/dl the apparatus gave precise results (co-efficient of variance 0.8%-6.4%), in good agreement with results by the hexokinase method. Reflocheck is an accurate and reliable instrument for the measuring of blood glucose levels.

Blood Chemical Analysis↗
PubMed1984

[Inborn and acquired metabolic disorders in human vascular cells in diabetes mellitus and hyperlipoproteinemia].

Fibroblast growth from diabetics with poor metabolic control is increased in vitro by 15-92% as compared to healthy age matched controls. In contrast, fibroblast growth from patients with different types of familial hyperlipoproteinemia is decreased by 9-83%. In these fibroblasts the activity of lysosomal cathepsin D, the key enzyme for LDL-apo B degradation, was decreased by 12-31% too. These cell associated alterations could be related to different stages of premature aging. Serum from type II diabetics with poor metabolic control (DS) and from hypercholesterolemics (HS) stimulated growth of human arterial smooth muscle cells and fibroblasts in vitro by 6-64% as compared to serum from healthy controls or to serum from diabetics with good metabolic control. DS increased in these vascular cells LDL- and HDL-binding up to 260%, but decreased LDL-apo B degradation by cathepsin D by 16-39% similar to HS that decreased it by 29-42%. These serum effects depend on the metabolic control and could stimulate the cell turnover. This growth effect of DS is mainly related to at least two new peptides of very low molecular weight (less than 2000 daltons), which might easily penetrate the arterial wall and could contribute to the increased angiopathic risk in diabetes.

Diabetes Mellitus↗