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T Kunt

Publications and source records attributed to T Kunt.

At least 19 recordsLinked to original sources

[Short-acting insulin analogs--critical assessment of meta-analyses].

Short-acting insulin analogs have for nearly ten years been prescribed for type 1 and 2 diabetes mellitus. There is extensive scientific and practical evidence of their being better than normal insulin. For this reason these insulins have been recommended in the guidelines of most leading specialist societies. In everyday practice they are an important component of the therapeutic portfolio which can produce an improvement in insulin treatment, especially of selective cases. On the other hand, there is growing economic pressure, especially in Germany, affecting their use. However, it must be critically asserted that those meta-analyses on insulin analogs, which have been commissioned by insurance companies or governmental organisations, do not do justice to their advantage. Current meta-analyses of short-acting insulin analogs exclude decisive advantages of insulin analogs from their analyses and compare highly heterogeneous groups. They do not distinguish between differing incidences of hypoglycemia associated with different HbA1c values as well as between conventional and intensive treatment. Furthermore positive data and positive major studies are excluded, while approval studies or trials with completely different aims are cited. Short study duration is also often neglected. As a result, the International Diabetes Federation (IDF) has rejected the Cochrane Review for 2005 for methodological reasons. Also, no recommendations can be derived from the recommendations of of the Institut für Qualitätssicherung und Wirtschaftlichkeit in der Medizin (IQWiG: Institute for Quality Assurance and Cost Effectiveness in Medicine). After critical assessment of meta-analyses the IDF concluded in its guidelines that insulin analogs should generally be used.

Diabetes Mellitus, Type 2↗

The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy.

Topical treatment with capsaicin cream has been shown to be successful in the treatment of different symptomatic nerve disorders like diabetic neuropathy. Conflicting data exist on the effect of capsaicin on nerve function and neurovascular control especially in patients with diabetic neuropathy. The aim of this pilot study was to investigate the impact of topical capsaicin application on small nerve fibre function and neurovascular control. Capsaicin cream was applied to the feet of 13 patients with symptomatic diabetic neuropathy over a period of 8 weeks. Before and during the treatment period, we investigated the total symptoms score, the vibration, thermal (heat and cold) and pain perception thresholds, and the neurovascular responses to heat and acetylcholine stimuli. In addition, the serum plasma levels of substance P, a neurotransmitter of nociceptor C-fibres, were measured. A significant improvement in total symptoms score was observed during topical capsaicin treatment (18.3+/-3.2 vs. 14.3+/-3.3; p<0.05). An improvement in the heat perception threshold was also found (12.7+/-0.4 degrees C vs. 11.4+/-0.7 degrees C: p<0.05), while other sensory nerve fibre functions remained unchanged. No significant change in neurovascular control was observed, neither after mild thermal injury nor after stimulation with acetylcholine. Serum substance P levels increased after initiation of topical capsaicin treatment (72.9+/-5.8 pg/ml vs. 81.7+/-5.0 pg/ml; p<0.05), but returned to baseline levels during further treatment (77.4+/-8.3 pg/ml: n.s.). In conclusion, topical treatment with capsaicin cream over a period of 8 weeks in patients with symptomatic diabetic neuropathy is effective without adverse effects on nerve fibre function or neurovascular control.

Administration, Topical↗

The influence of isolated small nerve fibre dysfunction on microvascular control in patients with diabetes mellitus.

AIM: The aim of the study was to investigate the influence of isolated small nerve fibre dysfunction on microvascular skin blood flow and transcutaneous oxygen tension in patients with diabetes mellitus. METHODS: Small nerve fibre dysfunction was assessed by the measurement of thermal and pain perception thresholds. Patients with evidence of large fibre disturbances as evaluated by means of vibration perception threshold were excluded from the study. Microvascular blood flow was investigated with laser-Doppler-fluxmetry (LDF) following stimulation with acetylcholine and mild thermal injury. RESULTS: Diabetic patients with small nerve fibre injury showed a significantly reduced increase in the laser-Doppler-flux signal following the application of acetylcholine compared with patients without neuropathy or healthy control subjects (2.8 arbitrary units (AU) (1.3-5.5) vs. 7.2 AU (4.1-25.5); P = 0.007 and vs. 8.5 AU (3.0-17.0), P = 0.02, respectively). The increase in LDF following thermal injury was also diminished in patients with small nerve fibre dysfunction compared with patients without neuropathy or the control group (29.8 AU (17.2-46.5) vs. 51.2 AU (29.5-93.5); P = 0.02 and vs. 54.6 AU (39.7-97.7); P = 0.004, respectively). In addition, they showed a significantly reduced transcutaneous oxygen tension compared with the other groups (42.9 mmHg (41.6-55.5) vs. 56.1 mmHg (49.2-60.8); P = 0.04 and vs. 59.0 mmHg (54.6-80.3), P = 0.03, respectively). CONCLUSIONS: Our study confirms an association between small nerve fibre injury and skin microvascular dysfunction. It further underlines the concept of neurovascular disturbances in the pathogenesis of neurotrophic foot ulceration. Diabet. Med. 18, 489-494 (2001)

Acetylcholine↗

Current strategies for controlling postprandial hyperglycaemia.

In patients with diabetes mellitus glycosylated haemoglobin (HbA1c), which reflects mean glycaemic values in the previous 3 months, is typically used as a clinical measure of blood glucose control. However, it does not always correlate satisfactorily with postprandial blood glucose excursions, which may occur only for a few hours and be insufficient to alter HbA1c formation. Thus, postprandial glucose peaks may have a significant impact on diabetic complications but not be monitored sufficiently from HbA1c measurements. Epidemiological studies have shown stronger correlations for incidence of cardiovascular events with postprandial glucose levels than with preprandial levels. Results from the UKPDS suggest that HbA1c had to be reduced below 7 per cent to ameliorate macrovascular outcomes. In patients with type 2 diabetes there is a loss of the first phase insulin response so a logical treatment strategy is to use a rapid-acting insulin analogue. Rapid-acting insulin analogues have a greater effect on postprandial glucose levels than regular human insulin. This is due to the faster absorption and higher insulin peak in blood, but also due to the increased ability of rapid-acting analogues to suppress hepatic glucose release. In clinical practice, preprandial injection of rapid-acting insulin reveals significant advantages including treatment flexibility, lack of weight gain, stable insulin doses and reduction of hypoglycaemic episodes. These effects are more pronounced if this type of therapy is used early in the course of the disease. Thus rapid-acting insulin analogues are being increasingly used as first-line therapy with multiple daily injection in patients with type 2 diabetes.

Coronary Disease↗

Assessment of some important anatomical variations and dangerous areas of the paranasal sinuses by computed tomography in children.

The purpose of this study is to determine important variations and areas of risk for major complications in paranasal computed tomography (CT). We also made specific measurements for individual differences. This study consisted of 64 children (128 sides). Eleven participants had coronal and axial, and the remaining 53 only coronal CT. The distance of the anterior ethmoidal artery (AEA) and the lamina cribrosa to the inferior turbinate and the orbital roof, and the depth of the lamina cribrosa were measured. The percentages of some of the variations were as follows: upper attachment of uncinate process 25%, freely coursing AEA 43%, aerated anterior clinoids 8%, optic canal bulging 6% and extreme medially coursing carotid canal 3%. The frequencies of some of these variations and the existence of Onodi cells were significantly smaller than compared with adults. Specific measurements varied individually. In conclusion, children deserve more attention while evaluating CT, due to their tiny bony structures.

Adolescent↗

[Comparison of hypoglycemia perception and hormonal counterregulation in controlled hypoglycemia. A contribution to diagnosis of hypoglycemia unawareness syndrome in type 1 diabetic patients].

BACKGROUND AND OBJECTIVE: Diabetics with abnormal hypoglycaemia awareness cannot recognize hypoglycaemic symptoms early and adequately enough to respond, thus endangering in everyday life not only themselves but also others. Thus it is important to diagnose such symptoms early and assess the extent to which the diabetic is at risk of severe hypoglycaemia. This study was designed to contribute to the evaluation of hypoglycaemia awareness in type 1 (IDDM) diabetics. PATIENTS AND METHODS: In 57 diabetics (IDDM) awareness of typical hypoglycaemic warning symptoms and of hormonal counterregulation were tested during controlled induced hypoglycaemia. A questionnaire was used to measure at fixed time intervals, along a four-point scale, the severity of 6 autonomic and 6 cerebral warning symptoms, and compare them with synchronously obtained plasma levels of glucagon and epinephrine. RESULTS: The cohort was divided into three groups according to the rise of epinephrine levels induced by the hypoglycaemia. Group A (n = 22) showed a significant rise in epinephrine level at the onset of hypoglycaemia; group B (n = 22): significantly increased epinephrine only after 30 min of hypoglycaemia; group C (n = 15): no epinephrine rise at any time during hypoglycaemia. None of the patients had a significant rise in glucagon levels. There were significant differences between the three groups regarding HbA1c levels and the duration of diabetes. Low levels of HbA1c and duration of diabetes were commonly associated with a loss of hormonal counterregulation. In only 40% of patients was it possible to draw any conclusion about epinephrine-induced hypoglycaemia from symptoms revealed in the past history. CONCLUSIONS: The past history of hypoglycaemic symptoms is an unreliable and inadequate guide for objectively assessing the actual risk of hypoglycaemia in type 1 diabetics. The results of this study indicate that when severe hypoglycaemic attacks (requiring outside help etc.) are suspected, standardized diagnostic tests of hypoglycaemia awareness should be performed in specialized centres, particularly if an official medical report ist required.

Adult↗

[Predictive genetic investigations. Individualization of diagnosis and treatment in families with multiple endocrine neoplasia type II].

BACKGROUND AND OBJECTIVE: When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. RESULTS: An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. CONCLUSION: These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.

Adolescent↗

Serum levels of substance P are decreased in patients with type 1 diabetes.

Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml; p<0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.

Adolescent↗

Improved diagnostic methods in the follow-up of medullary thyroid carcinoma by highly specific calcitonin measurements.

Calcitonin (CT) is an important tumor marker for medullary thyroid carcinoma (MTC). Recent CT assays chiefly recognize the monomeric form of CT (mCT). It was the objective of this study to examine the consequences of the higher specificity of the assay for interpretation of the postoperative CT values in MTC patients. The postoperative mCT concentration was measured in 214 patients with differentiated thyroid carcinoma (MTC excepted; non-MTC patients) to determine a reference range of mCT in totally thyroidectomized patients. Monomeric CT was also determined with a two-site chemiluminescence immunoassay (Nichols) in 94 healthy subjects and in 68 MTC patients. The mCT concentrations were below the detection limit in all examined completely thyroidectomized non-MTC patients. Basal and stimulated mCT values were also below the detection limit in 32 of the 68 MTC patients. The biochemical and imaging diagnosis of the latter patients did not give any indication of tumor recurrence. We conclude that completely thyroidectomized patients with non-MTC do not show any measurable mCT concentrations. In comparison with an unspecific CT-RIA, the more specific mCT determination by immunoluminometric assay permits a more precise differentiation between postoperative normal and pathological values and an earlier diagnosis of recurrent MTC.

Adult↗

Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I.

This study was conducted to evaluate the influence of proinsulin C-peptide on erythrocyte Na(+),K(+)-ATPase and endothelial nitric oxide synthase activities in patients with type I diabetes. In a randomized double-blind study design, ten patients with type I diabetes received intravenous infusions of either human C-peptide or physiological saline on two different occasions. C-peptide was infused at a rate of 3 pmol.min(-1).kg(-1) for 60 min, and thereafter at 10 pmol.min(-1).kg(-1) for 60 min. At baseline and after 60 and 120 min, laser Doppler flow (LDF) was measured following acetylcholine iontophoresis or mild thermal stimulation (44 degrees C), and venous blood samples were collected to determine plasma cGMP levels and erythrocyte membrane Na(+),K(+)-ATPase activity. The LDF response to acetylcholine increased during C-peptide infusion and decreased during saline infusion [18.6+/-19.2 and -13.2+/-9.4 arbitrary units respectively; mean+/-S.E.M.; P<0.05). No significant change in LDF was observed after thermal stimulation. The baseline plasma concentration of cGMP was 5.5+/-0.6 nmol.l(-1); this rose to 6.8+/-0.9 nmol.l(-1) during C-peptide infusion (P<0.05). Erythrocyte Na(+),K(+)-ATPase activity increased from 140+/-29 nmol of P(i).h(-1).mg(-1) in the basal state to 287+/-5 nmol of P(i). h(-1).mg(-1) during C-peptide infusion (P<0.01). There was a significant linear relationship between plasma C-peptide levels and erythrocyte Na(+),K(+)-ATPase activity during the C-peptide infusion (r=0.46, P<0.01). No significant changes in plasma cGMP levels or Na(+),K(+)-ATPase activity were observed during saline infusion. This study demonstrates an effect of human proinsulin C-peptide on microvascular function, which might be mediated by an increase in NO production and an activation of the erythrocyte Na(+),K(+)-ATPase. These mechanisms are compatible with the previous observed microvascular effects of C-peptide in patients with type I diabetes.

Acetylcholine↗

[Obesity: when does the internist recommend surgery?].

Obesity is a chronic disease with a poor therapeutical outcome. Well-defined education of the patient and conservative treatment are the basics of therapy. Nevertheless, one should always be aware of the possibility of surgical intervention. In the following, the diagnostical and therapeutical procedures concerning obesity will be described in order to allow a reasonable indication of surgical intervention.

Adult↗

Comparison of immunoassays for the detection of anti-GAD65 autoantibodies in patients with diabetes mellitus.

Recent studies have demonstrated that a combination of GAD-antibody assays and IA-2 autoantibody assays show a high diagnostic specificity for Type 1 diabetes. For this reason there is increasing interest in the use of GAD-antibody measurement for Type 1 risk assessment. Since a number of different assays have been published and documented in the literature, the aim of this study was to evaluate four different anti-GAD test systems that are commercially available in Germany. We tested the anti-GAD prevalences in five patient groups with the different immunoassays and compared them with the values obtained by an immunoprecipitation test (IP-Test). All assays correlated well with the IP-test and showed high sensitivity and specificity in the group of patients with recent onset Type 1 diabetes and the control group. The groups tested consisted of 20 subjects with recent onset Type 1 diabetes (< 6 weeks) (sensitivity 70-90%), nine subjects with a Type 1 duration of more than 2 years (sensitivity 11-33%), 21 patients with pluriglandular insufficiency (sensitivity 28.5-47.5%), 10 patients with Type 2 (specificity: 90-100%), and 14 healthy control subjects (specificity: 93-100%). Our data show a high level of sensitivity and specificity of the tested, commercially available, assays. Since almost every laboratory should be able to establish one of these assays, this may facilitate the possibility of further large scale population studies with the aim of investigating GAD-antibody prevalences in screening for Type 1 diabetes. Increased measurement of the diabetes-associated antibodies will be helpful in the differential diagnosis of gestational diabetes mellitus (GDM) and latent autoimmune diabetes of the adult (LADA).

Adolescent↗

The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus.

AIMS/HYPOTHESIS: In recent years, evidence has arisen that proinsulin C-peptide exerts biological effects especially on microcirculation, e.g. C-peptide has been shown to increase skin microcirculation in patients with Type I (insulin-dependent) diabetes mellitus and to activate endothelial nitric oxide synthase. This study aimed to investigate the influence of pro-insulin C-peptide on erythrocyte deformability which was assessed by means of laser diffractoscopy. METHODS: Blood samples from healthy control subjects (n = 10) and Type I diabetic patients (n = 15) completely deficient of C-peptide were analysed at shear stresses ranging from 0.3 to 30 Pa. RESULTS: Erythrocyte deformability was lower in the group of Type I diabetic patients than in the control subjects. Preincubation of the diabetic blood samples with various concentrations of human proinsulin C-peptide for 8 h restored the deformability of erythrocytes, almost reaching the values of control samples. In contrast, proinsulin C-peptide did not modify the erythrocyte deformability of control subjects. CONCLUSION/INTERPRETATION: We conclude that proinsulin C-peptide is able to ameliorate the impaired deformability of erythrocytes in Type I diabetic patients and we hypothesise that this effect is mediated by restoration of Na(+)-K(+)-ATPase activity, which is known to be attenuated in diabetic patients.

C-Peptide↗

Expression patterns of complex glycoconjugates and endogenous lectins during fetal development of the viscerocranium.

Experimental evidence suggests that carbohydrates and their corresponding receptors (endogenous lectins) decode biological information. Therefore, the expression of complex oligosaccharides--the potential ligand part of this recognition system--during chondrogenesis and osteogenesis was determined in the viscerocranium of fetal rats by mapping the staining patterns of exogenous lectins. Results were compared with the expression of bone- and/or cartilage-specific core proteins and the binding profiles of neoglycoconjugates. These synthetic tools make possible the localization of sugar-ligand-binding sites. The spatial and temporal distribution patterns of glycoconjugates were highly dynamic and demonstrated a clear correlation with characteristic morphological modifications. The glycobiological characterization of precartilage mesenchymal cells revealed distinct differences compared to prospective bone anlagen. Especially the binding of the exogenous lectin from Griffonia simplicifolia II, that selectively visualized prechondral aggregations, reveals that regulation of early chondral growth is at least phenomenologically correlated with a relatively atypical oligosaccharide composition terminating with N-acetylglucosamine.

Animals↗

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.

Adult↗

Detection of sarcolectin-specific receptors like the cytokine macrophage migration inhibitory factor in rheumatoid nodules.

The objective of this study was the evaluation of the relation between the N-acetyl-neuraminic acid-binding endogenous lectin sarcolectin and the cytokine macrophage migration inhibitory factor (MIF) during development of rheumatoid nodules (RN) in seropositive rheumatoid arthritis (RA). Sarcolectin was purified and biotinylated. The binding patterns of this probe were analyzed in RN from patients with RA (n = 23) and compared with the distribution of antibodies with specificity for MIF, fibrin, fibronectin. In early RN, all areas of the inflammatory tissue displayed presence of receptors for sarcolectin. Macrophages were especially positive. In mature rheumatoid nodules binding of sarcolectin was restricted to the periphery of necrotic areas, to endothelial cells and perivascular connective tissue of marginal zones. Distribution patterns of MIF were similar but not identical. The histological staining characteristics demonstrate sarcolectin-binding receptors in RN that are altered upon disease progression. The finding suggests that specific interactions between this endogenous lectin and MIF may be involved in the course of RA.

Adult↗

Germline mutations in the MEN1 gene: creation of a new splice acceptor site and insertion of 7 intron nucleotides into the mRNA.

The MEN1 tumor predisposition syndrome is caused by mutations in the MEN1 gene on human chromosome 11q13. We screened MEN1 gene exons 1-10 and flanking intron sequences from four different MEN1 families for mutations. In three families, heterozygous germline mutations within the exons were found, two of these representing novel mutations. In another family, all clinically affected members were heterozygous for a point mutation Gright curved arrow A within intron 4. Sequence analysis of cDNA from lymphocytes of the affected patients revealed that the intron mutation created a new acceptor splice site, leading to the inclusion of 7 bp of intronic sequence into the mRNA. The resulting frameshift generates a premature stop in codon 271. Intron borders should thus be screened for mutations in MEN1 diagnostics and cDNA sequence analysis is helpful in identifying pathophysiological consequences of intron mutations.

Alternative Splicing↗