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D Michaelis

Publications and source records attributed to D Michaelis.

At least 73 records · Page 4Linked to original sources
PubMed1988

Complement component 3 (C 3) and diabetes mellitus.

Complement factor 3 (C3) phenotype and allele frequencies were defined in 312 patients with Type 1 diabetes (IDDM), 256 patients with Type 2 diabetes mellitus (NIDDM), 114 apparently healthy first-degree relatives of Type 1 diabetics, in 10 families (29 members) with a familial history of Type 1 or Type 2 diabetes, and 512 controls (blood donors). All persons investigated were Europeans. There is no evidence to suggest that genes linked to C3 influence susceptibility to Type 1 and Type 2 diabetes and to their late complications. C3 levels in blood plasma were found to be slightly elevated in both types of diabetes. But the C3 concentrations varied considerably within the groups. C3 split products were demonstrable in a high percentage in the blood plasma of freshly manifested Type 1 diabetic persons as well as in Type 1 diabetics with a duration of the disease of 1 to 3 years. C3 proteolysis could also be found in plasma of Type 2 diabetics (26%).

Adolescent↗
PubMed1988

Restriction-fragment-length-polymorphisms close to the human insulin gene on chromosome 11 and their possible relation to diabetes mellitus in a GDR population.

A polymorphic DNA sequence flanking the 5'-region of the human insulin gene was studied by means of Southern blot hybridization techniques in 92 diabetic and non-diabetic individuals in order to investigate the possible relation of their allelic variants to certain types of diabetes. DNA was isolated from nucleated blood cells and digested with the restriction endonucleases EcoRI or Bg1 I. Only two classes of alleles were found (U and L). The small L-allele was predominantly found with the following frequency: 0.64 in controls, 0.795 in insulin-dependent diabetics, and 0.625 in non-dependent patients. It could be demonstrated that the L-allele and IDDM are associated. These data suggest that this allele seems to be a genetic marker for insulin-dependent diabetes mellitus. The putative function of the polymorphic region in the aetiology of diabetes mellitus and the possible genes being in linkage disequilibrium with it are not known so far.

Adult↗
PubMed1987

5-year follow-up study of C-peptide secretion in newly diagnosed type I diabetics: relations to HLA-phenotype, insulin requirement and metabolic control.

50 HLA-typed insulin-dependent diabetics were studied at the time of diabetes onset and after 1, 2, 3 and 5 years with regard to C-peptide secretion after combined stimulation with glucose and glucagon, insulin requirement and glycaemic control index. The mean decrease of the residual B-cell reserve was observed within two years. C-peptide secretion was correlated with better metabolic control and lower insulin requirement after more than one year of diabetes duration, but had no influence on this at the time of diabetes onset. The C-peptide response sometimes varied between non response and high response in one individual from one investigation to the next. There was no prognostic value of C-peptide secretion at diabetes onset for the further development of B-cell function. We found a significantly longer persistence of B-cell function in patients who were older and in those with mild symptoms at diabetes onset. The presence of HLA B8, DR3 antigens was correlated with severe ketoacidosis at manifestation and a more pronounced destruction of B-cell function.

Adolescent↗
PubMed1987

Complement-dependent antibody mediated cytotoxicity (C'AMC) in patients with newly diagnosed insulin-dependent diabetes mellitus.

Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were determined in 36 consecutive patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The sequential exposure of 51Cr labeled neonatal rat islet cells to patient serum and rabbit complement revealed the presence of C'AMC in 28 IDDM subjects. The C'AMC titres ranged between 1:4 and 1:512 and were not related to the C'AMC activity of a given sample as measured at a standard dilution (1:4). In comparison to the clinical characteristics of 21 IDDM patients with negative C'AMC, higher C'AMC titres (greater than or equal to 1:32) were associated with a lower mean age at diagnosis of IDDM (12.2 +/- 2.1 vs. 19.0 +/- 2.3 years; p less than 0.05), with a higher frequency of infections up to 6 months prior to diagnosis (6 out of 11 vs. 3 out of 21 patients; p less than 0.05) and, although statistically not significant, a preponderance of female sex together with a decreased frequency of HLA-DR4. In contrast, fasting C-peptides levels, HLA-DR3 antigen frequency and Coxsackie B1-6 virus antibody titres were not related to the C'AMC titres. It is concluded that (1) C'AMC titration is superior to the detection of initial C'AMC levels for evaluating the strength of the complement-dependent humoral immune response towards islet cell surface (auto)antigen(s), and (2) infectious agents may be involved in eliciting a C'AMC response.

Adolescent↗
PubMed1987

Islet cell surface antibodies (ICSA) in subjects with a previous mumps infection--a prospective study over a 4 year period.

It has been suggested that the mumps virus may be involved in the etiopathogenesis of Type-I diabetes mellitus. Most studies have analyzed this relationship retrospectively. We, however, carried out a prospective study over a 4 year period after a mumps infection in two age groups (16 years and under [group A no = 32] and over 16 years [group B no = 18]). These subjects with "diabetic risk factors" (impaired glucose tolerance, low insulin response, ICSA and/or HLA-DR3/DR4) were selected from 1581 registered cases, in whom an antecedent mumps infection had occurred in 1980 and 1981. Glucose tolerance and insulin secretion did not change significantly during 4 years after a mumps infection. Overt diabetes was not observed in any of the cases. One year after a mumps infection 35% of children and 63% of adolescents/adults exhibited ICSA (control subjects = 5%; a serum was considered ICSA-positive if more than 25% of the intact rat islet cells showed distinct cell surface immunofluorescence). After 4 years the percentage of subjects with ICSA decreased significantly to 13% and 14%, resp. Only 21% of ICSA-positive sera were found to be cytotoxic on rat islet cells (51Cr-release assay). No relationship could be evaluated between complications resulting from a mumps infection and the appearance of ICSA. There was no correlation between ICSA, glucose tolerance, and insulin secretion. In fact, our prospective study did not reveal any relationship between a mumps infection and Type-I diabetes. ICSA would seem to be of no predictive value.

Adolescent↗
PubMed1987

Cytotoxic islet cell autoantibodies in newly diagnosed insulin-dependent diabetes mellitus: lack of correlation to age, residual beta cell function, HLA antigens and Coxsackie B virus antibodies.

In a cross-sectional study comprising of 56 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) serum was examined for the presence of complement-dependent antibody mediated cytotoxicity (C'AMC) by an improved assay measuring the release of 51Cr from freshly isolated normal rat islet cells prelabeled with the isotope. In the presence of complement, 35 (63%) IDDM sera specifically mediated cytotoxicity against islet cells. The degree of cell specificity was tested using prelabeled exocrine cells, but this cell type did not reveal any differences between the lytic effects of IDDM and control serum. At the time of clinical onset of IDDM the age of the patients, fasting and stimulated C-peptide levels, insulin requirement, HLA antigens, antibodies to Coxsackie B1-6 viruses, diabetes heredity, and, surprisingly, islet cell surface antibodies (ICSA) were not associated with C'AMC. It is concluded that the mere presence of C'AMC against rat islet cells at the time of diagnosis of IDDM is not indicative of a low residual B cell function and HLA-linked susceptibility to diabetes does not necessarily include enhancement of humoral anti-islet cell autoimmunity. More elaborate methods for quantitative detection of C'AMC and ICSA (e.g. in terms of titres) together with autoantibody subclass determination are needed to reveal possible associations between C'AMC and the clinical characteristics of IDDM.

Adolescent↗
PubMed1987

Prevalence and incidence trends of non-insulin-dependent diabetes mellitus (NIDDM) in the population of the GDR.

Trends of prevalence and incidence rates of non-insulin-dependent diabetes mellitus (non-insulin-treated diabetes mellitus) were assessed in the population of the GDR based upon the National Diabetes Register and the Official Statistical Year Book as sources for the calculations. Within the 25-year follow-up period 1960-1984 the prevalence rose from 4.39%; to 31.95%; the incidence rate from 1.04%; to 3.57%. Age-dependence of the specific rates is characterized by their continuous rise above the age of 30 years reaching the peak prevalence of 146.6%; in 75- to 80-year-olds, that of 14.1%, for the incidence in people aged 70 to 75 years. A significant male preponderance was confirmed between the ages of 30 and 50 years, a significant overwhelming of female NIDDM in the age groups 60 to 90 years. Based on demonstrated correlations between the changes of living standard parameters and the epidemiological trend of NIDDM the conclusion is drawn that overnutrition and reduced muscular activity mainly account for the rise of diabetes morbidity in the population of the GDR.

Cross-Sectional Studies↗
PubMed1986

The role of insulin antibodies in insulin treatment of type I diabetes.

We investigated equilibrium plasma binding patterns of insulin in 45 juvenile diabetics treated with conventional insulin preparations. Insulin binding parameters were evaluated by Scatchard analysis of the binding data. Stable diabetics had significantly lower equilibrium dissociation constants than labile, thus suggesting an enhanced insulin depot effect due to stronger insulin binding. Correlation of insulin binding data with a glycemic control index yielded a positive relationship between insulin antibody binding and the degree of glycemic control. Insulin neutralization as detected by a relationship between maximum binding capacity of high affinity antibodies and insulin requirement could only be found if patients with poor diabetes control were excluded. Similarly, the well-known promoting influence of residual beta-cell functional capacity (assessed by C-peptide levels) on diabetic stability was observed only after exclusion of patients with higher insulin antibody binding. These data suggest that insulin antibodies are influencing insulin treatment of diabetics in a dual way. They may neutralize therapeutic insulin but at the same time they exert an insulin-sparing action by improvement of diabetes control. Occasionally the latter effect may abolish the correlation between diabetes control and beta-cell functional capacity.

Adolescent↗
PubMed1986

Age-dependent relationship of fasting C-peptide concentration and insulin secretion in non-obese subjects with normal glucose tolerance.

The age-dependent relationship of fasting immunomeasurable C-peptide to fasting immunomeasurable insulin (IRI) and IRI response to glucose was studied in 113 non-obese healthy subjects with normal glucose tolerance (oGTT according to the new WHO recommendations), ranging in age from 6 to 44 years. Fasting C-peptide concentration increased significantly in adolescents and adults when compared with children. The higher fasting C-peptide concentration in the adult group might be explained by the concomitant higher fasting blood glucose concentration whereas such relationship was lacking in adolescents. In contrast to this we failed to demonstrate such relationship with regard to fasting IRI levels. There was, however, a relationship between advancing age and early (IRI area 0-30 min), late (IRI area 30-120 min) and total (IRI area 0-120 min) insulin response to glucose. There was a significant correlation between fasting C-peptide concentration and estimates of IRI response in children and adolescents, whereas such relationship was lacking in adults. Based on these results, the present study demonstrates an age-related increase of the pancreatic beta-cell function which might be partly explained by the concomitant higher blood glucose concentration.

Adolescent↗
PubMed1985

[Prevention of diabetes mellitus with reference to its epidemiologic and etiopathogenic aspects].

With a prevalence rate of 36.4% the morbidity of diabetes occupies the 11th rank of the chronic non-communicable diseases in the population of the GDR. The 5.8-fold increase of the total prevalence which is to be observed in a period of 24 years is in 89% to be traced back to the increase of the non-insulin-dependent diabetes mellitus. Since unknown etiopathogenetic: events of IDDM exclude a secondary prevention in the sense of prevention of manifestation, it can already at present be used for the NIDDM with relevance to practice. First of all the preventive measures should concentrate on the prevention and removal, respectively of the peripheral insulin resistance by elimination of defined risk factors, which an inductor function in the course of the pathogenetic process to the NIDDM is to be ascribed to. The close hormonal and metabolic meshing of the pathogenesis of NIDDM with arteriosclerotic vascular diseases proves the demand for integrative combat programmes which are to be used on population scale.

Adolescent↗
PubMed1985

Validity of WHO criteria for classification of newly diagnosed diabetics.

In order to assess the validity of WHO criteria for the discrimination between Type I and Type II diabetes a cross-sectiona clinical study was performed in 84 normweight newly diagnosed diabetics with a mean age of 22 years. Taking into consideration clinical and biochemical characteristics of the carbohydrate and fat metabolism, the therapeutic requirement to maintain euglycemic metabolic control, the residual beta-cell function, the HLA phenotype and islet cell antibodies (ICA, ICSA) it could be shown that none of the tested criteria has the ability to distinguish between the types with absolute certainty. As shown by the frequency of the different markers in relation to the therapeutic requirements for euglycemic metabolic control as well as by the correlation analysis between the variables the discriminating validity of the markers decreased in the following sequence: diabetes associated HLA phenotype, residual beta-cell function, proneness to ketosis, age at onset, relative body weight. Neither the characteristics of the carbohydrate and fat metabolism nor the presence of islet cell antibodies contributed much to the differentiation between insulin-dependent and noninsulin-dependent diabetes.

Adolescent↗
PubMed1985

The frequency of islet cell surface antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) of mononuclear cells in HLA-typed patients with high diabetes risk.

To evaluate the significance of ICSA as a prognostic marker for the development of type I diabetes we investigated 66 subjects with first degree relatives of type I (47) and type II (9) diabetes as well as subjects with anamnestical data suggestive of diabetes. Patients were studied for glucose tolerance (oGTT) and IRI-response, ICSA (indirect fluorescence of living rat islet cell suspensions), ADCC (specific 51Cr-release of serum pretreated neonatal rat islets elicited by mononuclear cells) and HLA-antigens. 23 subjects revealed normal glucose tolerance, 17 impaired glucose tolerance and 26 had a prevoius abnormality. The incidence of ICSA varied between 46 and 53 per cent, that of positive ADCC between 22 and 56 per cent, both being highest in subjects with IGT. 87 per cent of all patients revealed diabetes associated HLA-antigens. We found no correlation of ICSA with glucose tolerance, IRI-response, ADCC and HLA-antigens. In conclusion it can be said that ICSA are present in a high percentage in patients with high diabetes risk but their predictive role as a marker for the manifestation must be elucidated in follow-up studies.

Adolescent↗
PubMed1985

[Diabetic lentopathy].

The authors report on lens opacities in 473 healthy children and in 371 children with type I diabetes mellitus. Only 11 percent of the healthy children had lens changes, whereas they were found in 65.6 percent of the children with diabetes mellitus. A large number of specific lens alterations were observed in the diabetic group. Examinations in the children with diabetes mellitus revealed that both the quality of metabolism and the duration of the disease influence the development of lens opacities, whereas age plays only a small part. On the basis of the study reported here a new classification of diabetic lentopathy is suggested.

Adolescent↗
PubMed1984

Long-term improvement in metabolic control of unstable type I diabetes by s.c. insulin injection patterns based on the dose profiles required by bed-side artificial beta-cell.

Twenty unselected unstable type I diabetic inpatients whose blood glucose control was insufficient employing three daily s.c. injections of regular insulin supplemented by intermediate acting insulin were subjected to a 48-hour treatment with the Biostator -GCIIS when both diet and muscular exercise were kept as close as possible to the conditions at home. The s.c. injection regimen was adjusted to the insulin dose pattern required by the artificial beta cell. There was significant metabolic improvement in 16 out of the 20 patients on discharge, in comparison to the pre-Biostator conditions. This improvement was still present when the patients were re-admitted after an average of seven months. It is concluded that in certain cases of unstable type I diabetes mellitus the metabolic re-arrangement based on intercalary days on an extracorporal artificial beta cell might be useful if the control constants are adapted to minimize the insulin requirement by the machine.

Adolescent↗
PubMed1984

Heterogeneity of insulin response in relatives of type-I and type-II diabetics.

In 30 first-degree relatives (siblings or children) of type-I diabetics and 17 relatives (children) of type-II diabetics as well as in 19 healthy subjects a two-hour glucose infusion test (GIT, 12 mg/kg b.w./min) primed by a starting bolus of 0.33 g/kg b.w. was performed to evaluate carbohydrate tolerance (CHT) and insulin secretion pattern. After 4 to 5 years the test was repeated and the results were compared with those of the initial GIT. The glucose-stimulated insulin response of the early secretion phase (0--5 min) decreased during the follow-up study in relatives of type-II diabetics with normal CHT (in tendency) and with glucose intolerance (p less than 0.05) but not in relatives of type-I diabetics. A rightward shift of the glucose-insulin response curve was seen in the former group. Relatives of type-II diabetics with impaired CHT showed a striking abnormality in B-cell responsiveness. In relatives of type-I diabetics a disturbed glucose-insulin response curve could not be observed. The insulin response during the late phase of insulin secretion did not differ significantly among the groups. The conclusion drawn from our findings is that responsiveness of pancreatic B-cells seems to be directly affected genetically in first-degree relatives of type-II but not of type-I diabetics. Thus, diabetes mellitus cannot be regarded as one disorder with a similar genetic background.

Adult↗
PubMed1984

Antibody-dependent cell-mediated cytotoxicity of mononuclear cells against Langerhans islets of Wistar rats in normal man and in patients at diabetes risk.

Antibody-dependent cell-mediated cytotoxicity against pancreatic islets was investigated in 13 newly diagnosed insulin-dependent diabetics, in 38 patients at high risk for the disease and in 20 age-matched healthy controls. For this purpose 51Cr-labeled neonatal rat pancreatic islets incubated with the specific anti-rat islet cell antiserum 339 or with serum of the lymphocyte donors were used as targets. The antibody-mediated cytotoxic activity of mononuclear cells was evaluated from the specific chromium release after 6 h exposure of pretreated islets to the effector cells. The specific cytotoxic effect of mononuclear cells from healthy controls on pancreatic islets pretreated with serum is weak. ADCC mediated by the specific antirat islet cell antiserum is significantly increased in 54% of newly diagnosed diabetics as well as in 32% of patients at high risk for insulin-dependent diabetes mellitus. 46% of the newly diagnosed diabetics were also ADCC-positive when their own serum was used for the pretreatment of islets, regardless of whether they were islet cell antibody- or islet cell surface antibody positive or not. Subsets of mononuclear cells (non E-rosette-forming cells, high affinity E-rosette-forming cells, low affinity E-rosette-forming cells) were prepared and their cytotoxic potential was analysed in patients with positive ADCC test results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗