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Biomedical subjects

D Michaelis

Publications and source records attributed to D Michaelis.

At least 55 records · Page 3Linked to original sources
PubMed1991

Glucose tolerance behaviour before the onset of type I (insulin-dependent) diabetes in young people as a predictor of the further course of the disease: a retrospective analysis of 33 cases.

A study was made of glucose tolerance and insulin secretion in 33 persons who later developed insulin-dependent diabetes (aged 4-24 years) and observation continued further in the first years after manifestation. Patients who developed the typical labile type of diabetes were of normal weight and had either normal glucose tolerance tests before diagnosis or had impaired glucose tolerance (IGT) for a short interval of 2-16 months. Subjects with IGT over a significantly (p less than 0.01) longer period of 32.30 +/- 6.25 (normal body weight) or 94.71 +/- 20.62 (obese) months developed a milder form of diabetes with retarded insulin dependency in obese subjects. The severe and mild form of IDDM are distinct with respect to insulin requirement (0.75 +/- 0.03 or 0.28 +/- 0.04 U/kg b.w., P less than 0.01) and glucagon stimulated C-peptide (0.18 +/- 0.05 or 1.41 +/- 0.27, P less than 0.01) in the first 2.5-3.5 years after onset. The two forms were not different regarding HLA-DR antigens. Islet cell surface antibodies investigated in 15 probands at 27 occasions before diabetes onset had no prognostic value. The development of a mild form of IDDM may be expected in cases with pre-existing IGT for more than one year. The insulin secretion is of low predictive value under these conditions. The observation is of practical use and theoretical interest.

Adolescent↗
PubMed1991

Effects of the platelet-activating factor antagonist BN 52021 on anti-islet cytotoxicity of mononuclear cells and serum from type 1 (insulin-dependent) diabetic patients.

The effect of platelet-activating factor (PAF) antagonist BN 52021 (0.06-2.5 mM) on the cytotoxic activity of mononuclear cells (MNC) from newly diagnosed type 1 diabetic patients against 51Cr-labeled Langerhans islets from neonatal rats was investigated in a 6-hour cytotoxicity test. A dose-dependent inhibition of anti-islet cytotoxicity by BN 52021 was observed. The suppression of the islet lysis was significant at a concentration of 0.6 mM BN 52021. During a 4-day cell culture, BN 52021 had no inhibitory effect on the antigen-mediated triggering of immunocytes with anti-islet cytotoxicity. The results suggest that the drug is only effective during immunocytolytic reactions of MNC against pancreatic islets. A PAF-independent action of BN 52021 can not be excluded at present.

Adolescent↗
PubMed1990

Trends in mortality rates in the diabetic population of the GDR.

Based upon the National Diabetes Registry the mortality rates were assessed annually between 1961 and 1987 in the total diabetic population of the GDR. The rise of diabetes prevalence from 724/10(5) up to 3988/10(5) during the 27-year observation period was associated with an increase of relative mortality rates from 466% to 600% in insulin-treated diabetics, from 352% up to 528% in non-insulin-treated diabetics. By calculation of standardized mortality ratios (SMR) it could be shown that excess mortality is dependent on age but not at all on sex. Insulin-treated diabetics exhibited their maximum SMR of 650% to 750% at ages 25 to 45 years, while in non-insulin-treated diabetics the maximum SMR amounted to 450% at ages 25 to 35 years. In contrast to trends of the total relative mortality rates that of the overall age structure adjusted SMR of diabetics was characterized by a declining tendency, which may be a reflection of the improvement in diabetes care in our country, and which underscores the dependence of mortal, ty rates on the methods used for evaluation.

Adolescent↗
PubMed1990

The higher frequency of type I (insulin-dependent) diabetes in fathers than in mothers of type I-diabetic children.

In 868 insulin-treated diabetic children and adolescents with onset of IDDM under age 20 we investigated the frequency of IDDM and NIDDM in all first-degree relatives. On the basis of the National Diabetes Register of the GDR the age-corrected lifetime risk for the development of IDDM and NIDDM was calculated for the general population and for parents and siblings of diabetic children. The age-corrected risk for IDDM, but not for NIDDM, is statistically significantly higher in fathers (10.26 +/- 1.75%) than in mothers (5.28 +/- 1.49%) and is about equal in brothers (30.71 +/- 6.07%) and sisters (35.54 +/- 6.28%) of children with IDDM. Among general population the age-corrected life-time risk for IDDM is equal for males (4.35 +/- 0.02%) and females (4.91 +/- 0.02%), but is significantly higher for NIDDM in females (27.49 +/- 0.04% contrary to 24.07 +/- 0.05%). In comparison with the data of Tillil and Köbberling (1987) our lifetime risk estimates show a shifting of risk for IDDM and NIDDM into older age groups.

Adolescent↗
PubMed1990

The frequency of disturbances of somatic development in young people with type I diabetes in dependence on duration and age at onset of the disease.

The height, weight and menarche of children and young people treated in the Children's Clinic as in-patients in 1987 was determined in dependence on the age at onset of diabetes and the duration of the disease, and the frequency of the disturbances of somatic development were shown. A growth retardation was registered in 1.8% only while the frequency of obesity amounted to 10%; 13.9% in female and 6.3% in male type I diabetics. However, the overall percentage of obesity in diabetics does not differ significantly from that in healthy subjects of corresponding age. With a higher age of onset, the frequency of adiposity increased significantly in both sexes; the highest frequency was shown by the girls who contracted the disease between the ages of 10 and 14. While the frequency of adiposity decreased significantly in male patients with increasing duration of diabetes, a non-significant increase was observed in female probands. There was no connection between adiposity and insulin dosage. The mean age for menarche in diabetic girls was determined at 13.4 years. The greatest, non-significant delay was experienced by those where onset of diabetes was between the ages of 5 and 9. The reason for this retardation is presumably the quality of the metabolism.

Adipose Tissue↗
PubMed1990

Autoantibodies against insulin (IAA), C-peptide (CAA), and glucagon (GAA) in new-onset type 1 diabetic patients.

Autoantibodies against insulin, C-peptide, and glucagon were determined by radio-binding assay in 63 new-onset Type 1 (insulin-dependent) diabetic patients as well as in 70 controls. Plasma peptide binding was determined by means of 125I-labeled peptides and charcoal-dextran separation technique. Binding values exceeding the mean plus three standard deviations of the controls were considered as antibody-positive. Sixteen patients (25%) were positive for IAA, as 6 (10%) were positive for CAA and 2 (3%) for GAA. Of all control subjects, none were positive for either IAA or CAA, whereas 2 (2%) had GAA. The mean 125I-glucagon binding in the patients' group was, however, slightly enhanced and could be suppressed to normal values by excess unlabeled glucagon. The presence of IAA and/or CAA was significantly associated with more severe symptoms at diabetes manifestation. These results indicate that in new-onset Type 1 diabetics autoimmunity arises against all the insular peptides tested but is predominantly directed against those antigens secreted from the beta cells. Nevertheless, extremely low-binding GAA seem to be common in these patients. The determination of IAA/CAA might be useful in detecting a possible heterogeneity of Type 1 diabetes with regard to its clinical mode of manifestation.

Age Factors↗
PubMed1990

Evaluation of metabolic control in type 1 (insulin-dependent) diabetic patients by estimation of serum fructosamine.

The method of Johnson et al. (1982) for the estimation of non-enzymatically glycated serum proteins (fructosamine test) was critically evaluated and modified with respect to photometric readings, incubation conditions, and standardization of the procedure. With this modified method, serum fructosamine concentrations were estimated in type 1 (insulin-dependent) diabetic patients whose glycemic control ranged from strictly to poorly controlled and in normoglycemic healthy control subjects. The mean fructosamine concentrations were for the control group (n = 52) 2.17 mmol/l (range 1.73-2.61 mmol/l) and for the diabetic patients (n = 432) 2.87 +/- 0.60 mmol/l (range 2.27-3.25 mmol/l). There were significant differences in fructosamine concentrations among the diabetic patients, corresponding to the degree of metabolic control. Serum fructosamine levels were closely correlated to the HbA1 levels. Compared with HbA1, fructosamine reflects short-term metabolic changes and appears to be an useful index of short-term glycemia.

Diabetes Mellitus, Type 1↗
PubMed1990

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes.

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.

Adult↗
PubMed1990

DQ beta restriction fragment length polymorphism in insulin dependent diabetes mellitus.

HLA DQ beta restriction fragment length polymorphisms (RFLP's) were compared in 43 patients with insulin dependent diabetes mellitus (IDDM), 51 healthy first grade relatives of IDDM patients and 27 controls without IDDM heredity in their families. We were able to demonstrate an association between the presence of a 12 kb BamHI restriction fragment (p less than 0.001) and 12 kb/4 kb (p less 0.01) or 12 kb/4.4 kb (p less than 0.001) BamHI fragment combinations and IDDM. But for these fragments and fragment combinations we also found increased frequencies in the healthy first grade relatives of IDDM patients. That means for the evaluation of the importance of the characterised "risk fragments" in practice it is necessary to follow up the manifestation of IDDM in this risk group.

Adolescent↗
PubMed1989

Alterations of purine metabolism in mononuclear cells of individuals at risk of developing type I (insulin-dependent) diabetes mellitus.

For the metabolic characterization of immunocompetent cells which are involved in the development of an insulin-dependent diabetes, a method for measurement of adenine uptake by mononuclear and macrophage-depleted mononuclear cell populations and of incorporation rates into the ATP, ADP, AMP and hypoxanthine fractions of these cells is presented and examined for its informative value in a cross-sectional study of individuals at risk of developing insulin-dependent diabetes. Values of 30 controls were compared with those of 53 risk persons. In controls and in 28 of the risk persons the adenine uptake by mononuclear cells was two to three times higher than that by the macrophage-depleted mononuclear cell population, suggesting high adenine metabolic activity of phagocytic cells. This activity was significantly decreased in the phagocytic cells of the remaining 25 risk persons. Additionally, the adenine incorporation rates into the adenine nucleotides of mononuclear cells were reduced by approximately 50% in these 25 risk persons. The alterations of purine metabolism were found associated with clinical symptoms of transient alterations of glucose tolerance and in the case of manifestation with a mild (HLA DR 3) type of insulin-dependent diabetes.

Adenine↗
PubMed1989

Persistence of anti-islet ADCC after manifestation of type-1 (insulin-dependent) diabetes.

ADCC (antibody-dependent cellular cytotoxicity) against xenogenic islets in vitro has frequently been found with mononuclear blood cells and heat inactivated autologous serum from newly diagnosed Type-1 diabetics. Anti-islet ADCC, as measured by enhanced 51Cr-release of islets after a 6h-incubation, leads to functional alteration of islets such as a decrease in insulin content and in leucine incorporation. In a follow-up investigation over at least three years it was demonstrated that anti-islet ADCC in vitro disappears, if there is no more C-peptide secretion in vivo. Furthermore, anti-islet ADCC has also not been found in long-term Type-1 diabetics who had no C-peptide secretion but an acutely stimulated immune system due to infectious diseases. An acute immunocytolytic process against pancreatic beta cells in vivo seems to be the precondition for anti-islet ADCC in vitro.

Adolescent↗
PubMed1989

Determination of islet cell surface antibodies in first-degree relatives of type 1 diabetic patients using rat insulinoma cells.

Titre of islet cell surface antibodies (ICSA) in 114 sera from healthy control probands and 177 sera from first-degree relatives of Type 1 diabetic patients was determined by indirect immunofluorescence using rat insulinoma (RIN) cells as target. All sera were tested at four dilutions (1/40-1/320). 10(5) RIN cells were incubated with 100 microliters diluted serum overnight at 4 degrees C followed by a 45 min-incubation with a FITC-labelled goat anti-human globulin. Titre curves were calculated by double logarithmic regression. ICSA titre was defined as the serum dilution producing cell surface fluorescence on 40% of RIN cells. Based on these data a serum is defined as ICSA positive when the ICSA titre calculated is higher than 1:142, quantil Q (0.97). Twenty-five out of 177 (14%) sera of first-degree relatives of Type 1 diabetes were ICSA positive with a mean titre of 1/393, range 1/145-1/1,740, while 2/114 (1.7%) control sera were weakly positive for ICSA. These data demonstrate the significantly increased ICSA prevalence in first-degree relatives of Type 1 diabetic patients. The present study suggests that RIN cells may represent a useful tool for standardization of ICSA assay.

Adolescent↗
PubMed1988

[Initial status of the medical management of pediatric and adolescent type I diabetic patients].

Based upon a large number of type I diabetics, representative of diabetes in childhood and adolescence of the GDR and taking into consideration communication in the literature, the present position is commented on autoimmune pathogenesis, immune intervention, frequency of complications, optimizing of therapy and on social-medical aspects of the diabetic child in school. Besides first degree diabetes heredity, degree of HLA identity with the index case, disturbances of glucose tolerance and insulin secretion, auto-immunological phenomena directed against islet cells have to be considered without doubt as risk factors for diabetes. But absolutely reliable markers of an imminent diabetes onset do not exist. The frequency of somatic retardations and diabetes-specific complications is low under multiple insulin injection regime, used in 87 per cent. However, their occurrence alone should stimulate to remove existing differences between clinical achievable metabolic compensation (good: 60%; bad: 2.5%) and longterm metabolic control (good: 40%; bad: 22%). In order to realize this aim, medical care is orientated mainly on qualification of patients and their parents to self-adaption of the insulin dose regime in dependence on values of home-monitoring.

Adolescent↗
PubMed1988

Phagocytic activity of blood cells in diabetic risk probands and newly diagnosed type 1 diabetics.

The phagocytic activity of granulocytes and mononuclear blood cells was compared in probands at risk for insulin-dependent Type 1 diabetes mellitus and in newly diagnosed diabetics before and during short-term insulin treatment. Healthy persons without family history of Type 1 diabetes were used as controls. Furthermore, the relationship between phagocytic activity and the proportion on monocytes in the granulocyte- and mononuclear blood cell fractions was estimated. The phagocytic activity of the mononuclear cells from the risk subjects was reduced. This observation suggests that defective phagocytosis might be important in the pathogenesis of Type 1 diabetes. But the phagocytic activity of mononuclear cells from newly diagnosed diabetics was not severely impaired and was fully normal under insulin treatment. We found no differences in the phagocytic activity of the granulocytes between patients and healthy probands. The proportion of monocytes in the mononuclear cell fraction was significantly enhanced in newly diagnosed diabetics and remained high throughout the 6-month period of insulin therapy. We assume that the increased monocyte level and the phagocytic activity of mononuclear cells in diabetics are not related to each other. But the increased monocyte level could also be interpreted as a compensatory reaction against the impaired phagocytic activity observed in the risk probands.

Adolescent↗
PubMed1988

Effect of lymphocytes and serum from probands before and after manifestation of type 1 (insulin-dependent) diabetes on rat islets in vitro.

In a two-year follow-up study neonatal rat islets have been shown to be affected in vitro by lymphocytes and complement-inactivated serum obtained from newly diagnosed Type 1 (insulin-dependent) diabetic patients and probands who are at high risk for developing the disease. The effect was measured by 51Cr-release of the islets treated with the proband's serum after a 6 h-incubation with lymphocytes of the same donor. Nineteen newly diagnosed diabetic patients, 23 persons at risk and 11 control probands were studied. There was no appreciable cytotoxic activity in the control probands (with one exception) and in 7 out of the 19 newly diagnosed diabetics. Five of the diabetes-susceptible probands developed diabetes mellitus during the investigation period. Anti-islet cytotoxicity of lymphocytes was found in these individuals at least 8 months before diagnosis of Type 1 diabetes. The cytotoxic effect disappeared at various time intervals after disease manifestation. Islet cytotoxicity was intermittently found with lymphocytes from further 13 probands at risk, sometimes for more than one year. Our data indicate that mononuclear cells from probands who are at high risk for developing Type 1 diabetes can exert cytotoxicity on xenogenic neonatal islets in the presence of their own serum.

Adolescent↗