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Biomedical subjects

K Schöffling

Publications and source records attributed to K Schöffling.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for pulsatile secretion of human atrial natriuretic peptide in healthy subjects.

The secretion pattern of human atrial natriuretic peptide (hANP) was investigated in 8 healthy male volunteers. Blood was drawn in 2 minute intervals for 90 minutes and in a second study in 4 minute intervals for 180 minutes. Base-line hANP plasma levels varied in a pulsatile secretion pattern of regular pulses every 9 +/- 1 minutes. Additionally long-term oscillations of 34 +/- 4 minutes were found. These data suggest that under basal conditions hANP varies in a pulsatile fashion.

Adult↗
PubMed1992

Delayed activation of D-glucose transport in type II diabetes mellitus.

Peripheral insulin resistance is suggested to play an important role in the pathogenesis of type II diabetes mellitus. In this study we investigated insulin receptor binding, D-glucose transport under equilibrium conditions for insulin and the activation kinetics of insulin stimulated D-glucose transport in isolated human adipocytes from type II diabetics and healthy controls. While the insulin receptor binding affinity was not significantly different between both groups, basal and insulin stimulated glucose transport rates were reduced in adipocytes from type II diabetics compared to normal controls. The activation of D-glucose transport was significantly delayed in the diabetics, the time to achieve maximal transport rates was 7.7 +/- 1.1 vs. 4.2 +/- 1.4 min, respectively (p < 0.05). Thus a reduced velocity of glucose transport activation by insulin appears to be a further factor contributing to peripheral insulin resistance in type II diabetics.

Biological Transport↗
PubMed1991

Prevalence of HLA-DQ beta chain non-Asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset.

Particular HLA-DQ beta chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogeneous German population, we studied HLA-DR specificities and HLA-DQ beta chain alleles in young-onset (less than 21 years of age; n = 185) and adult-onset (greater than 40 years of age; n = 48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQ beta chain was significantly associated with type I diabetes in both cohorts (etiologic fraction: 93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQ beta chain provides a molecular risk marker for type I diabetes of both and adult onset.

Adolescent↗
PubMed1991

[Somatomedin C level and stimulation of growth hormone and adrenal cortex function by administration of releasing hormones and physical exertion in patients with obesity].

In a clinical study on potential determinants underlying the impairment of growth hormone stimulation in obese human subjects, we examined in 20 otherwise healthy adult obese subjects (14 females, six males, age 18 to 40 years, body mass index greater than 29 kg/m2) the responses of growth hormone (hGH), adrenocorticotropic hormone (ACTH) and cortisol to releasing hormone stimulation (growth hormone-releasing hormone and corticotropin-releasing hormone) and the responses of hGH, ACTH, cortisol and free fatty acids (FFA) to physical exercise. Subjects with somatomedin-C levels less than or equal to 0.7 U/ml (group 1) were more obese than subjects with somatomedin-C levels greater than 0.7 U/ml (group 2) (p less than 0.01). In group 1, hGH increased by 4.3 +/- 1.2 ng/ml in response to releasing hormone administration and by 0.9 +/- 0.3 ng/ml in response to physical exercise (normal responses, increase by greater than 7 ng/ml), in group 2, hGH increased by 6.7 +/- 1.4, and 2.4 +/- 0.8 ng/ml, respectively (p less than 0.05 vs. group 1). Moreover, FFA stimulation by physical exercise was blunted in group 1 (p less than 0.05 vs. group 2). In contrast, ACTH stimulation was found increased in group 1 in comparison to group 2, particularly in response to physical exercise (p less than 0.01), and resulted in enhanced cortisol stimulation (p less than 0.05). Thus, impaired hGH stimulation in obese human subjects is not explained by an altered relationship between hGH and somatomedin-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immunogenetic markers in patients with Graves' disease.

110 carefully characterized Caucasoid patients with Graves' disease were tested for HLA class I and class II antigens. Compared with Caucasian controls (n = 193), the frequencies of HLA B8, Cw7 and DR3 were significantly increased (pc less than 0.05). In the subgroups with and without exophthalmos, HLA A3 exhibited a negative but insignificant association with the eye involvement, while A19 and Cw2 showed positive, however even weaker correlations with eye disease. HLA DR5 was associated with relapsing thyrotoxicosis, whereas HLA DR7 and B12 were negatively correlated with relapse. These results confirm the positive correlation of HLA B8 and DR3 with Graves' disease and reveal a not yet observed association with Cw7. Reported correlations of antigen frequencies with eye disease and relapsing thyrotoxicosis could not be confirmed. Other previously unknown, however subtle differences in disease subgroups were observed.

Alleles↗
PubMed1991

[The influence of autonomic diabetic neuropathy and human atrial natriuretic peptide on adrenal gland function in postural changes].

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.

Adult↗
PubMed1991

Aspartic acid at position 57 of the HLA-DQ beta chain is protective against future development of insulin-dependent (type 1) diabetes mellitus.

Insulin-dependent (Type I) diabetes mellitus is a chronic autoimmune disease. From studies in discordant twins and multiplex families a long prediabetic period has been reported. In a population-based program started in 1983, fifteen individuals at possible risk for future Type I diabetes were followed for up to 74 months. Two individuals (13%) developed Type I diabetes. These probands were characterized by the presence of high-level cytoplasmic islet cell antibodies (ICA), complement-fixing ICA, and an impaired first-phase insulin response after intravenous glucose load. Both were homozygous for a high-risk immunogenetic marker of Type I diabetes, i.e., non-Asp at codon 57 of the HLA-DQ beta chain. In all other subjects studied, the immunogenetic marker that confers "dominant resistance", aspartic acid at codon 57, was found. On the basis of our data we conclude that a combination of assays which determine ICA, first-phase insulin release, and HLA-DQB1 polymorphisms will identify individuals with a high probability of developing Type I diabetes at the population level. Conversely, HLA haplotypes positive for aspartic acid seem to confer resistance to the disease.

Adult↗
PubMed1991

[Long-term antihypertensive treatment in diabetes mellitus. Results with the calcium antagonist felodipine].

In 17 hypertensive, insulin-treated diabetics (eight type 1 diabetics, nine type 2 diabetics) the effectiveness of 10 mg/day felodipine was investigated over a period of one year. In both groups, felodipine brought about a lasting decrease in blood pressure (p less than 0.05). After four weeks' treatment, type 1 diabetics experienced a 143% increase in albumin excretion, and an 83% increase in fractional albuminuria, as compared with the initial values (p less than 0.05). In type 2 diabetics, in contrast, albumin excretion decreased by 25%, fractional albuminuria by 48% (p less than 0.05; p less than 0.01, as compared with type 1 diabetics). After 28 weeks of treatment, the fractionale albuminuria in the two groups had decreased by 27% (p less than 0.05 compared with the short-term response) and 37%, respectively. No change in hormone or metabolic parameters was observed.

Adult↗
PubMed1991

Beat-to-beat variation of heart rate in diabetic patients with autonomic neuropathy and in completely cardiac denervated patients following orthotopic heart transplantation.

Dysfunction of the vagal nerve, an early symptom in the development of autonomic neuropathy, can be assessed reliably by the beat-to-beat variation in heart rate. Patients after a cardiac transplantation are a unique model to investigate the beat-to-beat variation of a completely denervated heart. Heart rate and the beat-to-beat variation during normal and deep respiration were investigated in diabetic subjects with an autonomic neuropathy (n = 10), age and sex matched healthy controls (n = 10) and cardiac transplanted patients (n = 10). Further studies during pharmacological blockade of the parasympathetic nervous system with atropine were performed. In the denervated heart the coefficient of variation of the beat-to-beat interval was 0.38 +/- 0.02% during normal respiration, compared to 1.32 +/- 0.13% (P less than 0.0001) and 2.56 +/- 0.13% (P less than 0.0001) in the diabetic and control subjects, respectively. Administration of atropine (2 mg intravenously) decreased the coefficient of variation of the RR-interval to 0.73 +/- 0.09% in the diabetic patients (P less than 0.0005) and to 0.67 +/- 0.07% in the controls (P less than 0.0001), whereas the coefficient of variation remained unaffected in the cardiac denervated patients (0.39 +/- 0.02%). In the three groups an almost parallel increase of the RR-variation was observed during deep respiration at a rate of 6 breaths/min (from 0.38 +/- 0.02% to 1.99 +/- 0.38% in cardiac transplanted patients, P less than 0.0025; from 1.32 +/- 0.13% to 3.10 +/- 0.43% in diabetic patients, P less than 0.0025; from 2.56 +/- 0.13% to 5.42 +/- 0.94% in healthy controls, P less than 0.005). We conclude that a beat-to-beat variation of heart rate is present in the completely denervated heart. This RR-variation can not be influenced by a pharmacological blockade of the parasympathetic nervous system with atropine. The beat-to-beat variation increases during deep respiration not only in healthy controls but also in diabetic patients with autonomic neuropathy (partially denervated hearts) and cardiac transplanted patients (completely denervated hearts). This indicates an intracardiac mechanism in the modulation of heart rate.

Atropine↗
PubMed1991

The HLA-DQ beta non-Asp-57 allele: a predictor of future insulin-dependent diabetes mellitus in patients with autoimmune Addison's disease.

HLA-DR specificities in 72 Addison's (AD) patients and 808 local controls were compared. We confirmed earlier reports that the HLA-DR3 specificity is significantly increased in AD patients. In our study a relative risk of 3.4 chi 2 = 22.5; pc = 0.01) for the disease was calculated. Analysis of HLA-DQB1 alleles in DR4+ Addison's patients with diabetes mellitus (N = 6) and without IDDM (14 of 18 individuals tested) revealed that the HLA-DQw8 allele (DQB1*0302) was significantly increased in AD patients with IDDM (chi 2 = 13.5; p = 0.001); conversely, a clustering of the HLA-DQw7 allele was detected in DR4+ Addison's patients without IDDM. We thus conclude that particular polymorphic alleles corresponding to non-charged amino acids at position 57 of the HLA-DQ beta-chain [non-Asp-57 alleles] are associated with IDDM also in Addison's patients.

Addison Disease↗
PubMed1991

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Adolescent↗
PubMed1990

[Long-term treatment of acromegaly with the somatostatin analog octreotide (Sandostatin). On the predictive significance of acute tests].

Twelve acromegalic patients were treated (mean +/- SD) 26 +/- 15 months with daily doses of 440 +/- 330 micrograms of the somatostatin analogue octreotide acetate (SMS 201-995, Sandostatin). The levels of somatomedin-C (Sm-C) decreased by 63% from 8.1 +/- 7.7 U/ml to 3.0 +/- 1.3 U/ml. Before starting therapy a long oral glucose tolerance test (oGTT) and a TRH test were performed both without and after s.c. injection of 100 micrograms octreotide. Under long-term treatment with octreotide four of twelve patients reached normal Sm-C-values. The GH levels of all of these patients were continuously suppressed to less than 2 ng/dl in an oGTT after a test dose of 100 micrograms octreotide s.c. till the end of the test (5 1/2 hours after octreotide injection). The other eight patients had a relief of acromegalic symptoms and five had a decrease of their Sm-C-levels, but none of them reached normal Sm-C-values. None of these patients had a continuous suppression of GH after a test dose of octreotide in an oGTT. Hyperprolactinemia (n = 4) was observed only in those patients with an insufficient response to octreotide. The GH-response to TRH showed neither without nor after injection of octreotide a correlation with the results of long-term treatment. Thus it is concluded that GH-suppression in a long oGTT after administration of a test dose of 100 micrograms octreotide acetate s.c. allows to identify those acromegalic patients who will benefit from long-term treatment with the somatostatin analogue octreotide acetate.

Acromegaly↗
PubMed1990

[Compliance problems in therapy with levothyroxine].

In order to evaluate problems with long-term levothyroxine therapy, the course of treatment in 185 patients of an endocrinological outpatient ward (88 with euthyroid goiter, 41 with overt or latent hypothyroidism, ten with Hashimoto's thyroiditis, 46 after resection of goiter) was analyzed retrospectively. Duration of therapy ranged from one to 28 years. Suppressive therapy of euthyroid goiter was stopped by the treating physician in eleven patients (11%), in five permanently. To the contrary, 30 patients (34%) stopped medication by themselves 31 times, 29 times, however, levothyroxine was restarted again. Observations in the group with latent hypothyroidism were similar. After operation levothyroxine therapy was stopped by the physician eight times, six times only for a limited time period. Eight patients (17%) decided to stop therapy without knowledge of the treating physician, but in all it was restarted later. The presented results show that the success of levothyroxine therapy of euthyroid goiter as well as of prophylaxis of goiter relapse after operation is threatened by dyscompliance of the patients. In goiter suppression therapy compliance is further challenged by a lack of consequence in therapy planning and guidance.

Adolescent↗
PubMed1990

[The effect of atrial natriuretic peptide on glucose tolerance and insulin level].

In previous studies, a pharmacological dose of human atrial natriuretic peptide (hANP) was found to increase serum insulin without influencing C-peptide levels. To examine whether blood glucose and insulin response to an oral or i.v. glucose load are influenced by raising hANP levels into the pathophysiological range, eight healthy, normal-weighted, male volunteers were studied. According to a randomized, double-blind study design, an oral glucose tolerance test (ogtt, 75 g) or an i.v. glucose tolerance test (ivgtt, 0.5 g/kg b.w.) were carried out. Beginning 30 minutes before glucose administration infusions of hANP 0.3 micrograms/min) or placebo were given for 180 minutes (ogtt) or 120 minutes (ivgtt). During the hANP-infusions maximal hANP levels were 72 +/- 11 pg/ml (normal less than 25 pg/ml). Responses of blood glucose and C-peptide levels to the glucose load remained unaffected by hANP in both studies. However, hANP increased mean insulin responses (given as area under the curve) by 11.5% in ogtt and by 15.9% in ivgtt (both p less than 0.05). Thus, elevated hANP levels within the pathophysiological range, as observed in chronic heart failure or in hypertension, lead to an increase in serum insulin. Unchanged C-peptide levels demonstrate that hANP does not interfere with insulin secretion, but exclusively inhibits insulin degradation in liver and/or kidney. Further studies are required to elucidate whether these findings play a part in the pathomechanisms of insulin resistance in patients with elevated hANP levels, e.g. in chronic heart failure or hypertension.

3-Hydroxybutyric Acid↗