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Biomedical subjects

E Standl

Publications and source records attributed to E Standl.

At least 73 records · Page 4Linked to original sources
PubMed1996

Value of ICA512 antibodies for prediction and diagnosis of type 1 diabetes.

ICA512 was isolated from an islet cDNA expression library and was identified as transmembrane protein closely related to the T-cell tyrosine phosphatase CD45. In order to determine the frequency of antibodies (ab) to ICA512, we tested sera of 124 newly diagnosed type 1 diabetic patients (IDDM) and 30 patients with long standing IDDM, 44 non-diabetic first degree relatives (FDR) with positive ICA or IAA, and 76 healthy control subjects using an ELISA. The mean +/- SD that we obtained in our control population was 4.1 +/- 3.9 U and a cut-off of 16 U was defined as normal range (mean + 3 SD). Of newly diagnosed diabetic patients and patients with long standing IDDM, 32% and 23% respectively had positive ICA512-ab with a mean of 22 +/- 33 U (vs controls p < 0.001) and 14 +/- 14 U (p < 0.01). Of antibody-positive first degree relatives, 36% were found to have elevated ICA512-ab with a mean of 24 +/- 41 U (p < 0.01). In relatives with multiple follow-up samples, ICA512-ab were found to be constantly positive or negative in 86% of cases, whereas fluctuation of ICA512-ab positivity occurred in five relatives in which three developed positive ICA512-ab and two lost ICA512-ab positivity during follow-up. Of ICA512-ab + relatives, 76% progressed to clinical type 1 diabetes within 5 years of follow-up, whereas only 24% developed diabetes in the ICA512-ab negative group (p < 0.01). ICA512-ab were more frequent in newly diagnosed diabetic children below age 15 years (p < 0.02) and in patients with positive ICA (p < 0.001) or positive IAA (p < 0.02). There was, in contrast, no correlation of ICA512-ab with GADA. One patient with newly diagnosed type 1 diabetes exclusively exhibited ICA512-ab. In conclusion, these results suggest that ICA512-ab are related to autoimmune type 1 diabetes and useful as an additional screening marker for the prediction of type 1 diabetes.

Adolescent↗
PubMed1996

Reduced myocardial 123I-metaiodobenzylguanidine uptake in newly diagnosed IDDM patients.

123I-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy is a novel technique for the assessment of cardiac sympathetic dysinnervation. To evaluate defects of the cardiac autonomic nervous system at the onset of IDDM, this technique together with conventional electrocardiogram (ECG)-based cardiac reflex tests and measurement of the QT interval was applied to 22 newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion abnormalities (99mTc-labeled methoxyisobutylisonitrile scintigraphy) and 9 matched control subjects. Seventeen diabetic patients (77%), but none of the control subjects, were observed to have a reduced global myocardial uptake of 123I-MIBG. In contrast, only two diabetic patients (9%) demonstrated an ECG-based cardiac autonomic neuropathy (two or more of five age-related cardiac reflex tests abnormal) (P < 0.001). In newly diagnosed IDDM patients, the uptake of 123I-MIBG was reduced more in the posterior myocardial region compared with the lateral and apical region (P < 0.01, P = 0.03). The septal myocardial region exhibited a smaller uptake than the lateral myocardial region (P = 0.02). The maximum/minimum 30:15 ratio correlated with the global, anterior, lateral, and septal myocardial uptake of 123I-MIBG (P < 0.05, P < 0.05, P < 0.01, P < 0.05). A correlation between global and regional myocardial 123I-MIBG uptake and HbA1c or QT interval was not observed. Newly diagnosed metabolically stabilized IDDM patients without myocardial perfusion defects show evidence of cardiac sympathetic dysinnervation, as indicated by a reduction of 123I-MIBG uptake, at a significant higher proportion than ECG-based cardiac autonomic neuropathy. Furthermore, they present with regional differences of myocardial 123I-MIBG uptake.

3-Iodobenzylguanidine↗
PubMed1995

Scintigraphic evidence for cardiac sympathetic dysinnervation in long-term IDDM patients with and without ECG-based autonomic neuropathy.

To analyse the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in long-term insulin-dependent diabetes mellitus (IDDM) without myocardial perfusion abnormalities (99mTc-methoxy isobutyl isonitrile study), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy was performed in two clinically-comparable groups (20 diabetic patients with and 22 diabetic patients without ECG-based cardiac autonomic neuropathy). For comparison nine control subjects without heart disease were investigated. Only six diabetic patients (27%) without and one diabetic patient (5%) with ECG-based autonomic neuropathy were found to have a uniform homogeneous uptake of 123I-MIBG, in contrast to a uniform homogeneous uptake in all control subjects. The uptake of 123I-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral and septal myocardium (p < 0.001, p < 0.001, p = 0.001). In addition, diabetic patients with cardiac autonomic neuropathy (> or = two of five age-related cardiac reflex tests abnormal) demonstrated a more reduced uptake in the global, lateral and posterior myocardium than diabetic patients without (p < 0.01, p < 0.01, p < 0.001). A correlation between global or regional myocardial 123I-MIBG uptake, however, and duration of diabetes, HbA1c, body mass index or QT interval length was not observed. Our study demonstrates that cardiac sympathetic dysinnervation is common in long-term IDDM even in patients without ECG-based cardiac autonomic neuropathy and that the posterior myocardium is predominantly affected. We conclude that 123I-MIBG scintigraphy is a promising approach to further elucidate the pattern and natural history of myocardial dysinnervation in IDDM.

3-Iodobenzylguanidine↗
PubMed1995

Hypertension in the non-insulin-dependent diabetes mellitus syndrome: a critical review of therapeutic intervention.

BACKGROUND: Since it is not yet clear whether and to what degree treatment of mild hypertension will decrease cardiovascular morbidity and mortality in non-insulin-dependent diabetes (NIDDM), decisions concerning the treatment of hypertension diabetics are at present based on data from the non-diabetic population. RECENT RESEARCH ON CAUSES OF DIABETES: A large body of recent work on the sequence of events leading from the prediabetic to the hyperglycemic stages of the NIDDM syndrome has suggested that elevated blood pressure and other cardiovascular risk factors may precede NIDDM by many years and that after the onset of NIDDM intervention might be too late to be beneficial. PROSPECTIVE INTERVENTION STUDY IN PROGRESS: It is not possible to draw firm conclusions that can be applied to the treatment of hypertensive diabetics before the results of the United Kingdom Prospective Diabetes Study/Hypertension in Diabetes Study are published later this decade. Unfortunately, this study does not consider different stages within the NIDDM syndrome. Moreover, World Health Organization criteria are not used for the diagnosis of either NIDDM or hypertension, so that the study subjects are insufficiently characterized. Finally, confounding variables such as racial, ethnic and sex differences and the individual stage of the NIDDM syndrome (and consequent variation in antidiabetic treatment) have been either not considered or not completely ruled out. These shortcomings seriously threaten the significance of this otherwise important study. CONCLUSIONS: As long as there are no diabetes-specific data from adequately sized intervention studies, recommendations for antihypertensive treatment in NIDDM will be based on strategies accepted for the non-diabetic population. These recommendations involve symptom-based diagnostic and therapeutic concepts of both NIDDM and hypertension and ignore recent pathogenetic concepts which could lead to an interdisciplinary and integrated approach to cardiovascular risk management, and possibly to the prevention of end-stage NIDDM syndrome with its advanced macrovascular complications.

Antihypertensive Agents↗
PubMed1995

Hyperinsulinemia and atherosclerosis.

Studies of macrovascular disease in non-insulin-dependent diabetes (NIDDM) have shown a significant increase in peripheral vascular, coronary, and carotid artery disease in diabetics compared to non-diabetics. This prevalence appears to be related to insulin levels and to the degree of hyperinsulinemia as measured in the blood of these patients. Indeed, a cluster of markers, including hyperinsulinemia, insulin resistance, hypertension, dyslipoproteinemia, and a high waist-hip ratio, has been associated with NIDDM and increased risk for macrovascular disease. Variously described as Metabolic Syndrome or Syndrome X, this syndrome may be operative for many years before NIDDM is diagnosed. Given the complexity of Metabolic Syndrome, a single-factor intervention for preventing macrovascular disease in NIDDM is unlikely. However, it seems advisable to screen, on a regular basis, all patients presenting a pre-NIDDM state, as well as those with overt NIDDM, for pertinent cardiovascular risk parameters and for emerging macrovascular disease. It is suggested that any attempt to prevent macrovascular disease in subjects with glucose intolerance should aim at decreasing insulin resistance and hyperinsulinemia.

Arteriosclerosis↗
PubMed1994

[How can primary prevention of coronary heart disease be improved in general practice?].

BACKGROUND: The basic issue of primary prevention strategies of coronary heart disease is an individually adapted cardiovascular risk factor management. However, transformation of these strategies by health care professionals is still insufficient, as was demonstrated by three studies performed in private practice. METHODS AND RESULTS: In oral glucose tolerance tests performed in 234 patients with essential hypertension who were under regular medical control, 25.6% turned out to have previously unknown diabetes and 41.4% had impaired glucose tolerance. In the remaining 33.3% with normal glucose tolerance, mean total serum cholesterol was 260 mg/dl. 82 patients with essential hypertension and known diabetes had a mean total serum cholesterol of 276 mg/dl. Neither cohort was under lipid lowering drugs. Out of 290 unselected patients treated for type II-diabetes in private practice, 62% were hypertensive. Of those, hypertension was not known untreated or not sufficiently treated in 78.2%. CONCLUSION: As a consequence, in patients at high cardiovascular risk, not only the "leading" disease (i.e. diabetes, hypertension, hyperlipidaemia), but also the concomitant constellation deserves attention and early intervention.

Adult↗
PubMed1994

Alterations of lymphocyte subsets in children of diabetic mothers.

To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM): 48 with gestational diabetes), including 22 neonates, 45 infants aged 8-12 months, 46 children aged 1-2 years, 29 children aged 3-6 years and 18 children aged 7-17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p = 0.044), T and B lymphocytes (p = 0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n = 15) or gestational diabetes (n = 7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p = 0.006; B lymphocytes: p = 0.008). In cord blood, 45.5% of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA1 during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67-73% of the cases above and 62-77% below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother.

Adolescent↗
PubMed1994

Associations of anti-GAD antibodies with islet cell antibodies and insulin autoantibodies in first-degree relatives of type I diabetic patients.

Sera from 114 first-degree relatives of insulin-dependent diabetes mellitus (type I diabetes) patients and 81 healthy individuals living in Germany were analyzed for antibodies to rat brain glutamic acid decarboxylase (GAD-ab) using an immunoprecipitation assay. The determination of GAD-ab in the 81 islet cell antibody (ICA) and insulin autoantibody (IAA) negative healthy individuals established a normal range (mean +/- 2 SD); 2 healthy individuals (2.5%) possessed GAD-ab levels above this range, but became negative on follow-up. None of 86 ICA-/IAA- first-degree relatives had GAD-ab; whereas, 42.9% of 28 ICA+ and/or IAA+ relatives were positive for GAD-ab. Presence of GAD-ab was negatively correlated with IAA (P = 0.02) and positively with ICA (P = 0.0006). Follow-up samples were obtained from 25 of 28 ICA+ and/or IAA+ relatives with a mean (+/- SD) follow-up period of 20.6 +/- 12.1 months. In these 25 relatives, GAD-ab were positive in 70% ICA+/IAA-, 0% ICA-/IAA+, and 57.1% ICA+/IAA+ relatives in the first sample and in 57.1% ICA+/IAA-, 0% ICA-/IAA+, and 70% ICA+/IAA+ relatives in the last sample. GAD-ab, once detected, persisted in 9 of 11 GAD-ab+ relatives. Of the relatives, 2 converted to GAD-positivity, concomitant with the appearance of ICA, and 2 others lost GAD-ab during follow-up. Of the 28 ICA+ and/or IAA+ relatives, 6 progressed to overt type I diabetes on follow-up, and GAD-ab were detectable in 4 of these relatives.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[The metabolic syndrome. Pathophysiologic causes, diagnosis, therapy].

The individual components of the metabolic syndrome such as central obesity, dyslipidemia with increased triglycerides and decreased HDL-cholesterol, hyperuricemia, hypertension and progressive glucose intolerance are markers for an increased risk of atheroma and type 2 (non-insulin-dependent) diabetes. All components, with the exception of hyperuricemia, are associated with skeletal muscle insulin resistance, leading to compensatory chronic hyperinsulinemia. Insulin resistance/hyperinsulinemia, in turn, is associated with a series of hypertensiogenic and atherogenic side effects, aggravating the individual components of the metabolic syndrome. From a more pathophysiologically orientated point of view, early identification of individuals obviously at risk for atheroma and type 2 diabetes, as well as early intervention aimed at the improvement of reduced insulin action may play a central role in an integrated life-style approach of primary prevention of atherosclerosis and type 2 diabetes.

Arteriosclerosis↗
PubMed1993

On the appearance of islet associated autoimmunity in offspring of diabetic mothers: a prospective study from birth.

For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n = 113) and gestational diabetes (n = 55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies > or = 20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies > 49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies > or = 20 JDF-U, 76% insulin antibodies > 49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies > or = 20 JDF-U, 18% insulin antibodies > 49 nU/ml; neonates: 13% islet cell antibodies > or = 20 JDF-U, 55% insulin antibodies > 49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Microalbuminuria in a random cohort of recently diagnosed type 2 (non-insulin-dependent) diabetic patients living in the greater Munich area.

Still under debate is the prevalence of microalbuminuria in patients with recently diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and its relation to existing macro-vascular disease and the major vascular risk markers. Hence, from a representative sample of 1512 patients with Type 2 diabetes of varied duration (recruited from 22 non-specialized medical practices of the Greater Munich Area) 68 (26 males, 42 females) of 71 eligible subjects with a known duration of diabetes of up to 17 weeks and not less than 4 weeks were examined in the present study. Median age was 61 (39 to 75) years, prevalence of ischaemic heart disease (case history plus ECG, Minnesota code, Whitehall criteria) 41.2%, and that of peripheral vascular and carotid artery disease (both assessed by ultrasound-Doppler) were 35.3 and 4.4%, respectively. Diabetes was well controlled (HbA1c: 6.9%, 5.6-8.3; fasting blood glucose: 7.7 mmol/l, 5.4-10.4; median +/- interquartile range IQ), the cardiovascular risk profile was most prominent in terms of triglycerides (3.1 mmol/l, 2.1-4.6, median +/- IQ range) and systolic blood pressure (164 mm Hg, 140-186, median +/- IQ range). 13.2% showed signs of urinary tract infection. Of the remainder, 19.0% exhibited microalbuminuria (RIA, > 30-200 mg/l), and 5.2% macroalbuminuria (> 200 mg/l). Significant correlations (p < 0.05) were found between urinary albumin concentration and beta 2-microglobulin in serum, systolic blood pressure, serum triglycerides, serum HDL-cholesterol (inversely), HbA1c, and peripheral vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Dermatoglyphics in type 1 diabetes mellitus.

Although fingerprints and handprints are widely used in criminology, it is only recently that this approach has been applied to the field of medical and genetic diagnoses. In order to investigate dermatoglyphics in Type 1 diabetes mellitus, quantitative characteristics of fingers and palms (ridge count and main line indices) as well as qualitative parameters such as digital and interdigital patterns, the position of the palmar axial triradii and main line courses were analysed in 88 male and 108 female Type 1 diabetic patients and compared with data from 100 male and 99 female normal controls. Type 1 diabetic patients show a lower third finger ridge count (p < 0.05) and a-b ridge count (p < 0.001) and higher transversality of the main lines as indicated by the main line index value (p < 0.001) or the ending of the main line A in a specific sector 5, 5', and 5" (p < 0.001) compared with controls. In addition, diabetic patients show higher frequency of palmar axial t' and t" triradii (p < 0.001) and a lower frequency of 'true' patterns in the fourth interdigital and thenar area (p < 0.001) than controls. By multivariate analysis of quantitative and qualitative variables a predictive value of 78.6% and 77.3%, respectively, for male, and 81.4% and 82.2%, respectively, for female Type 1 diabetic patients was found. In conclusion, dermatoglyphics seem to be an interesting tool for genetic studies related to Type 1 diabetes.

Dermatoglyphics↗
PubMed1993

Hypertension and insulin resistance. Glycaemia and insulinaemia in overweight hypertensive patients.

The relationship between insulin resistance and hyperinsulinaemia on one hand and hypertension on the other hand has become apparent during the last few years. Insulin resistance, which may be genetically determined, is, according to our present understanding, the 'key player' in the metabolic syndrome. However, the pathophysiology of the combination of factors has not yet been fully elucidated. Early therapeutic intervention for insulin resistance, hyperinsulinaemia and hypertension may prevent the clinical manifestation of non-insulin-dependent (type 2) diabetes. Preliminary results of an ongoing study investigating the effects of trandolapril or the diuretic combination of hydrochlorothiazide and triamterene on serum glucose and insulin levels are presented.

Antihypertensive Agents↗